Metal Complexes with Naphthalene-Based Acetic Acids as Ligands: Structure and Biological Activity

Abstract

Naproxen (6–methoxy–α–methyl–2–naphthaleneacetic acid), 1–naphthylacetic acid, 2–naphthylacetic acid and 1–pyreneacetic acid are derivatives of acetic acid bearing a naphthalene-based ring. In the present review, the coordination compounds of naproxen, 1– or 2–naphthylacetato and 1–pyreneacetato ligands are discussed in regard to their structural features (nature and nuclearity of metal ions and coordination mode of ligands), their spectroscopic and physicochemical properties and their biological activities.

1. Introduction

Carboxylates are intriguing ligands since they may offer two carboxylato oxygen atoms to form up to four metal–oxygen bonds resulting in interesting structures. Depending on the nature of the carboxylato ligands and in combination with the choice of metal ions, the resultant metal complexes may present interesting properties from many points of view, such as magnetic, photochemical, and biological properties [1,2,3,4,5,6,7,8]. Among the carboxylato ligands, the acetato ligands and their derivatives are the most studied ones, leading to a variety of metal complexes, nuclearities and properties [7,8,9].

As a continuation of our previous perspective and review articles [10,11] concerning the structures and biological properties of metal complexes with carboxylato antimicrobial and anti-inflammatory drugs as ligands, a search of the Cambridge Crystallographic Data Centre (CCDC) database regarding the structures of metal complexes with acetato ligands was performed. Our attention was drawn by the presence of the fused polycyclic aromatic hydrocarbon ring on the acetato derivatives which gave a series of interesting metal complexes. Therefore, a thorough search of the CCDC database [12] was recorded and revealed a series of metal complexes with acetato ligands which are attached to a naphthalene or a pyrene ring (Figure 1). From the point of view of the acetato ligands, only four compounds used as ligands were found, i.e., 1–naphthylacetic acid, 2–naphthylacetic acid, naproxen and 1–pyreneacetic acid (Figure 2).

In the present review, the structural features (nature and number of metal ions, coordination mode of ligands and nature and coordination of co-ligands) and the physicochemical and spectroscopic characterization as well as the properties and potential (mainly biological) applications of the reported metal complexes of the 1–naphthylacetato, 2–naphthylacetato, 1–pyreneacetato and naproxen ligands will be presented and discussed.

2. Information on the Acids, Co-Ligands and Metal Ions

2.1. General Considerations for the Acids

Naphthylacetic acids (naphthoic acids or naphthaleneacetic acids, HNA) are compounds containing a planar naphthalene ring bound to an acetic group. Based on the position of the aromatic ring where the acetic group is located, they are characterized either as 1–naphthylacetic acid (α–naphthylacetic acid, HN1A) or 2–naphthylacetic acid (β–naphthylacetic acid, HN2A) (Figure 2). Both HNAs are white amorphous solids and are mainly used as plant growth regulators [13]. They are synthetic plant auxin hormones and are commercially used in agriculture and house-gardening as rooting agents [14]. As typical compounds of the auxin family, their use and concentration should be controlled since they may become toxic to plants at higher concentrations and to animals at lower concentrations [15]. 1–naphthylacetic acid has a more extended use than 2–naphthylacetic acid. An important advantage of 1–naphthylacetic is its stability, since, before its entrance in the tissue, it is not destructed by light or by oxidation [16]. The main actions of 1–naphthylacetic acid comprise the activation of cell division, cell elongation, photosynthesis, RNA synthesis, membrane permeability and water uptake in plants [13]. Therefore, 1–naphthylacetic acid is often used to increase the production by lowering and delaying the preharvest drop of crops and hanging fruits and improving their quality (e.g., apples, olives, oranges and hazelnuts [17,18]). Another function of both HNAs is their involvement in the formation of flower buds of tobacco [16] and pistachio plants [19]. In addition, 2–naphthylacetic acid is the main initial metabolite of anaerobic degradation of naphthalene and 2–methylnaphthalene from sulfate-producing bacteria [20].

Naproxen (6–methoxy–α–methyl–2–naphthaleneacetic acid, HNAP, Figure 2) is an established non-steroidal anti-inflammatory drug (NSAID) [21]. It is a common anti-inflammatory, analgesic and antipyretic medicament and is administered for the treatment of painful dysmenorrheal [22], chronic migraine, kidney stones, rheumatoid arthritis and osteoarthritis [23]. The use of naproxen induces milder side effects regarding increased blood pressure compared to ibuprofen [24] or celecoxib [25] and stomach ulcers compared to indomethacin [26] and other NSAIDs [27]. Naproxen may produce analgesic and anti-inflammatory effects by blocking non-selectively both cyclooxygenase (COX) enzymes (COX–1 and COX–2) [28,29] and subsequently decreasing the synthesis of prostaglandins [21]. The absorption of naproxen is rapid and complete upon oral or rectal administration [21,30]. Recently, a carbon nanotube functionalized by cationic hyperbranched polyethyleneimine was examined as a potential effective carrier of naproxen [31].

1–Pyreneacetic acid (HPYA, Figure 2) is a pyrene derivative. The pyrene ring is the smallest peri-fused polycyclic aromatic hydrocarbon [32] and, because of its 16 π–electrons [33], it may provide interesting electronic properties [34] exploitable for various applications such as the preparation of chemosensors [35]. In particular, the reaction of 1–pyreneacetic acid with N–hydroxysuccinimide resulted in the formation of a Pd(II)–thioether amide chemosensor having high selectivity over Pd(0) [36]. The photoluminescence of 1–pyreneacetic acid (emission band with λ_max ~400 nm, when excited at 345 nm) was also taken into consideration for the fabrication of dual-functionalized polymer nanotubes which could act as substrates for molecular probes and DNA carriers [37]. Recently, 1–pyreneacetic acid was used for the functionalization of a graphene/self-assembled monolayer modified gold electrode which could be used for the study of electron transfer of cytochrome c by electrochemical techniques [38]. 1–Pyreneacetic acid has also been proposed as a titrating reagent for the titration of organolithium and Grignard reagents [39] since the end point of such titrations is significantly accurate [40].

2.2. The Co-Ligands

Besides the four acids, i.e., 1–naphthylacetic acid, 2–naphthylacetic acid, naproxen and 1–pyreneacetic acid, used as the main ligands in the complexes under study, another thing that is significant is the role of co-ligands in these complexes, since the number of binary complexes is very limited and most of them are mixed ligand complexes. Most of the co-ligands found in the reported complexes were either O–donor ligands or N–donor ligands, and, in few cases, P–, B– or C–donors were also found.

Among the O–donor ligands, the most frequently found are those originating from a solvent used, i.e., H₂O, methanol (CH₃OH), N,N–dimethylformamide (DMF), dimethylsulfoxide (DMSO) or tetrahydrofuran (THF) (Figure 3). In certain cases, oxygen atoms were also provided in combination with nitrogen atoms by N^O–donor co-ligands such as salicylhydroxamic acid (H₃shi), pyridin–3–ol (pyr3OH), di(2–pyridyl)ketone oxime (Hpko) and 3–pyridylmethanol (3pym) (Figure 4).

The nitrogen–donor co-ligands were found in most of the reported metal complexes under study. Their choice was mainly based on their structures, since in many these co-ligands contained single or fused aromatic rings which may have led to better stabilization of the structure due to the formation of π–π interactions with the naphthalene or pyrene rings of the acetato ligands, and on their potential synergism regarding other properties, such as photochemical and biological applications. The nitrogen–donor co-ligands may be categorized into the following:

(i)

Imidazole derivatives, including imidazole (Himi) and compounds containing a 5-membered heterocyclic aromatic ring, such as 1,2–dimethylimidazole (1,2–dmimid), 1H–benzimidazole (Hbzmd), caffeine (caf) and 3,5–dimethylpyrazole (Hdmpz) (Figure 5);

(ii)

Pyridine derivatives, including pyridine (py) and compounds containing a 6-membered heterocyclic aromatic ring, such as 2–picoline (2pic), 3–picoline (3pic), 4–picoline (4pic), 2–aminopyridine (2ampy) and 2,2′–bipyridylamine (bipyam) (Figure 6), or 2,2′–bipyridine derivatives including 2,2′–bipyridine (bipy), 4,4′–bipyridine (4,4′–bipy), 5,5′–dimethyl–2,2′–bipyridine (5,5′–Me₂–bipy) and 1,3–bis(4–pyridyl)propane (bpp) (Figure 7), as well as 1,3–dipyridin–3–ylurea (3U), 1,3–dipyridin–4–ylurea (4U), 2,4–diamine–6–phenyl–1,3,5–triazine (phdat) and tris(2–pyridyl)amine (TPA) (Figure 8);

(iii)

2,2′:6′,2″–terpyridine derivatives, including 4′–(4–tolyl)–2,2′:6′,2″–terpyridine (L1), 4′–(furan–2–yl)–2,2′:6′,2″–terpyridine (L2), 4′–(pyridin–3–yl)–2,2′:6′, 2″–terpyridine (L3), 4′–(4–chlorophenyl)–2,2′:6′,2″–terpyridine (L4), 4′–(3,4–dimethoxyphenyl)–2,2′:6′,2″–terpyridine (L5) and 4′–(4–dimethylaminophenyl)–2,2′:6′,2″–terpyridine (L6) (Figure 9);

(iv)

Phenanthroline derivatives, including 1,10–phenanthroline (phen) and its derivatives 2,9–dimethyl–1,10–phenanthroline (neocuproine, neoc) and 4,7–diphenyl–1,10–phenanthroline (4,7–diPhphen) (Figure 10);

(v)

Alicyclic or aliphatic nitrogen–donors, such as 1,4,8,11–tetraazacyclotetradecane (cyclam), 1,4,7–trimethyl–1,4,7–triazacyclononane (TACN–Me₃), tris(2–aminoethyl)amine (tren) and N,N–dimethylethane–1,2–diamine (EDA) (Figure 11).

The use of the phosphines triphenylphosphine (PPh₃) and tri(p–tolyl)phosphine (tptp) was also noted in some cases, while the hydrotrispyrazolylborate (Tp⁻) ligand and the polydentante 1,3–diamino–2–hydroxypropane–N,N,N′,N′–tetraacetic acid (H₅dhpta) were noticed each in one structure (Figure 12). Diverse alkyl and aryl ions such as n–butyl (n–Bu), methyl (Me) and phenyl (Ph), as well as CO, were used as carbon atom donors.

2.3. Metal Ions of the Reported Complexes

Among the existing metal ions, a significant number of metal ions have been used to prepare coordination compounds with 1–naphthylacetato, 2–naphthylacetato, 1–pyreneacetato and naproxen ligands (Figure 13). The common first row transition metal ions were used in the majority of the reported metal complexes, i.e., Ti(IV), Mn(II/III), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II). Coordination compounds with the second and third row transition metal ions Y(III), Ru(II/III), Ag(I), Cd(II) and Au(I) were also isolated and studied. The complexes of most lanthanide(III) ions (i.e., Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III) and Yb(III)) have also been found in the literature. From the s- and p-block of the periodic table, few Mg(II) and Sn(IV) compounds have also been reported.

All of these metal complexes were structurally characterized mainly using single-crystal X-ray crystallography and some basic spectroscopic and physicochemical techniques. Most of the lanthanide(III) complexes were studied for their photochemical properties, while many transition metal complexes, especially of the NSAID naproxen, were monitored for their potential biological potency.

3. Structures of the Complexes

The main features of the structures of the reported complexes are the coordination mode of the carboxylato ligands under study and the nuclearity of the resultant metal complexes, as well as the geometry around the central metal ions and the connectivity between them in the non-mononuclear compounds.

For the purposes of the present study, the reported complexes were categorized based on (i) the metal nuclearity and (ii) the coordination mode of the acetato ligands. Most of the complexes were either mononuclear or dinuclear. Among the polynuclear complexes, structures for trinuclear, tetranuclear, hexanuclear and polymeric complexes have been reported in the literature. Considering the acetato ligands, diverse (either one or more than one) coordination modes have been observed in each complex.

3.1. Coordination of the Carboxylato Ligands

Concerning the coordination of the four acids studied herein in their coordination compounds, their carboxylate group is deprotonated. The potential coordination to the metal ions may be summarized to the different binding modes which are typical for carboxylato ligands, shown in Figure 14.

They may be bound in the following ways: (i) monodentately via a carboxylato oxygen atom (κ–O) (Figure 14A), (ii) chelating bidentately via the two carboxylato oxygen atoms (κ–O,O′) (Figure 14B), (iii) bridging bidentately via one carboxylato oxygen atom (µ–O,O) forming a monoatomic bridge (Figure 14C), (iv) bidentately bridging two metal ions via the two carboxylato oxygen atoms (µ–O,O′) forming a M–O–C–O–M’ bridge (Figure 14D), (v) tridentately bridging two metal ions via the two carboxylato oxygen atoms (µ₂–O,O,O′) forming a M–O–C–O′ chelate ring and a M–O–M’ bridge (Figure 14E), (vi) tridentately bridging three metal ions via the two carboxylato oxygen atoms (µ₃–O,O,O′) forming a M–O–M’ bridge and a M’–O–C–O–M’’ bridge (Figure 14F), (vii) tetradentately bridging three metal ions via the two carboxylato oxygen atoms (µ₃–O,O,O′,O′) (Figure 14G) and (viii) tetradentately bridging four metal ions via the two carboxylato oxygen atoms (µ₄–O,O,O′,O′) (Figure 14H). Of the eight potential binding modes, the first six fashions (i)–(vi) were found in the crystal structures reported in the literature and will be presented in the corresponding section.

3.2. Mononuclear Complexes

Many of the complexes reported in the literature are mononuclear and contain transition metal ions (Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Ag(I), Cd(II) and Au(I)), lanthanide ions (Gd(III), Eu(III) and s-block (Mg(II)) and p-block metal ions (Sn(II)) [41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64].

In most of the mononuclear complexes, the carboxylato group is monodentately bound to the metal ion (

Table 1. Mononuclear complexes of 1–naphthylacetato, 2–naphthylacetato and naproxen ligands. Coordination mode of the ligands, CCDC name of the complex, coordination sphere and geometry of the metal ions.

Complex	CCDC Name	Coordination Sphere of Ion M	Geometry of Ion M a	Reference
I: Monodentate coordination of the ligands
[Mg(NAP–O)2(H2O)4]	ANOMIA	MO6	Oh a	[41]
[Mn(NAP–O)2(py)2(H2O)2] b	GIKLEU	MN2O4	Oh	[42]
[Co(NAP–O)2(py)2(H2O)2]	KATSUV	MN2O4	Oh	[43]
[Co(NAP–O)2(cyclam)]	TEMKUU	MN4O2	Oh	[44]
[Cu(N1A–O)2(Hdmpz)2]	HOGTII	MN2O2	Spl	[45]
[Cu(NAP–O)2(H2O)3]·H2O	ZASZAW	MO5	Spy	[46]
[Cu(N1A–O)(EDA)2](ClO4)	TUFTUL	MN4O	Spy	[47]
[Cu(NAP–O)2(H2O)(4pic)2]	RANHOG	MN2O3	Spy	[48]
[Cu(NAP–O)(L1)Cl]	RUHJIP	MN3OCl	Spy	[49]
[Cu(NAP–O)(L2)Cl]	BUSYEV	MN3OCl	Spy	[49]
[Zn(NAP–O)2(H2O)2]·H2O	ZASZEA	MO4	Td	[46]
[Ag(NAP–O)(PPh3)3]·H2O	QIZWED	MOP3	Td	[50]
[Au(NAP–O)(PPh3)]	ZICVIU	MOP	L	[51]
[Gd(N1A–O)2(phen)2(H2O)2]·[Eu(N1A–O)2(phen)2(H2O)2]·(N1A)2·2H2O	HOFMEW	Co-crystallized/MN4O4	Dh	[52]
II: Bidentate chelating coordination of the ligand
[Mn(N1A–O,O′)2(Hbzmd)2]·H2O	LANDEL	MN2O4	Oh	[53]
[Ni(N1A–O,O′)2(Hbzmd–N3)2]·H2O	YAVLIS	MN2O4	Oh	[54]
[Cu(NAP–O,O′)2(4,7–diPhphen)]	EYIKAA	MN2O4	Oh	[55]
[Cu(NAP–O,O′)2(bipy)]·H2O	LEBVIZ	MN2O4	Oh	[56]
[Cu(NAP–O,O′)2(phen)]·H2O	LEBVOF	MN2O4	Oh	[56]
[Zn(N1A–O,O′)2(phen)]	NEQLIF, NEQLIF01	MN2O4	Oh	[57,58]
[Ag(NAP–O,O′)(tptp)2]	QIZWAZ	MO2P2	Td	[50]
[Cd(NAP–O,O′)2(H2O)2]·H2O	ZASZUQ	MO6	Oh	[46]
[(n–Bu)2Sn(NAP–O,O′)2]	XISCAF, XISCAF01	MC2O4	Oh	[59,60]
III: Monodentate + bidentate chelating coordination of the ligands
[Mn(NAP–O)(NAP–O,O′)(phen)(H2O)]	GIHJEP	MN2O4	Oh	[42]
[Ni(NAP–O)(NAP–O,O′)(bipy)(H2O)]	YAQJEI	MN2O4	Oh	[61]
[Ni(NAP–O)(NAP–O,O′)(phen)(H2O)]	YAQJAE, GADYET	MN2O4	Oh	[61,62]
[Zn(NAP–O,O′)2(neoc)]	NORBED	MN2O3	Spy–TB	[63]
[Zn(N1A–O)(N1A–O,O′)(5,5′–Me2–bipy)]	UQUSAB	MN2O3	Spy–TB	[64]

^a Dh = dodecahedral; L = linear; Oh = octahedral; Spl = square planar; Spy = square pyramidal; TB = trigonal bipyramidal; Td = tetrahedral; ^b 4pic = 4–picoline; 4,7–diPhphen = 4,7–diphenyl–1,10–phenanthroline; 5,5′–Me₂–bipy = 5,5′–dimethyl–2,2′–bipyridine; bipy = 2,2′–bipyridine; cyclam = 1,4,8,11–tetraazacyclotetradecane; EDA = N,N–dimethylethane–1,2–diamine; Hbzmd = 1H–benzimidazole; Hdmpz = 3,5–dimethylpyrazole; L1 = 4′–(4–tolyl)–2,2′:6′,2″–terpyridine; L2 = 4′–(furan–2–yl)–2,2′:6′,2″–terpyridine; n–Bu = n–butyl; neoc = neocuproine = 2,9–dimethyl–1,10–phenanthroline; phen = 1,10–phenanthroline; py = pyridine; tptp = tri(p–tolyl)phosphine.

, part I), representative complexes are shown in Figure 15). However, in many of the reported mononuclear complexes, the carboxylato group of the ligands is bidentately chelating and coordinated to the metal ion (Table 1, part II), complexes shown representatively in Figure 16). In addition, in five complexes [42,61,62,63,64], a combination of these two binding modes was observed; one ligand was monodentately bound and the second one was bidentately chelating and coordinated (Table 1, part III), examples shown in Figure 17). Almost all of these mononuclear complexes were neutral with the exception of the cationic complex [Cu(N1A–O)(EDA)₂](ClO₄) [47].

All of these mononuclear complexes are heteroleptic and the coordination spheres of the central metal ions are completed by oxygen atoms of the N1A⁻, N2A⁻ or NAP⁻ ligands and O, N, P or C atoms derived from appropriate co-ligands that served as O–donors (H₂O), N–donors (Figure 5, Figure 6, Figure 7, Figure 8, Figure 9, Figure 10 and Figure 11), P–donors (triphenylphosphine or tri(p–tolyl)phosphine) or C–donors (n–butyl), respectively.

The coordination number (CN) of the central metal ion and subsequently its geometry differs and is dependent on the nature of the metal. It varies from two (for Au(I) in complex [Au(NAP–O)(PPh₃)] [51]) up to eight (for the lanthanide ions Gd(III) and Eu(III) in co-crystallized complexes [Gd(N1A–O)₂(phen)₂(H₂O)₂]·[Eu(N1A–O)₂(phen)₂(H₂O)₂](N1A)₂·2H₂O [52]). Considering the geometry around the central metal ions, diverse cases were observed depending on their coordination number. For CN = 2, a linear arrangement of the ligands was observed in complex [Au(NAP–O)(PPh₃)] [51]. For CN = 4 (coordination sphere: MN₃O, MOP₃, MN₂O₂, MO₂P₂ and MO₄), distorted tetrahedral geometry was observed for the Zn(II) and Ag(I) ions and distorted square pyramidal geometry was observed for the Cu(II) ions in their complexes. Five-coordinate metal ions (coordination sphere: MN₂O₃, MN₃OCl, MN₄O and MO₅) were observed in Cu(II) and Zn (II) complexes bearing a distorted square pyramidal geometry around the metal ions. Distorted octahedral geometry was observed for six-coordinate metal ions resulting from a variety of coordination environments (MC₂O₄, MN₄O₂, MN₂O₄ and MO₆). In the case of the lanthanide(III) complex, eight-coordination was observed (MN₄O₄) resulting in a distorted dodecahedral geometry.

3.3. Dinuclear Complexes

Significant also is the number of the dinuclear complexes with 1–naphthylacetato, 2–naphthylacetato, naproxen and 1–pyreneacetato ligands found in the literature (

Table 2. Dinuclear complexes of 1–naphthylacetato, 2–naphthylacetato, naproxen and 1–pyreneacetato ligands. Coordination mode of the ligands, CCDC name of the complex, oxidation state and coordination sphere of the metal ions.

Complex	CCDC Name	Metal Ions	Coord.Sphere	Reference
I: Bidentate bridging (μ–O,O′)
[Fe2(µ2–O)(µ2–N2A–O,O′)(tren)2](BPh4)(NO3)2	MAXXUF	Fe(III)2	MN3O2	[65]
[Fe2(µ2–O)(µ2–N2A–O,O′)(TPA)2](ClO4)3	MAXYAM	Fe(III)2	MN3O2	[65]
[Fe2(µ2–O)(µ2–N2A–O,O′)2(Tp)2]	MAXYEQ	Fe(III)2	MN3O3	[65]
[Fe2(µ2–O)(µ2–N2A–O,O′)2(TACN–Me3)2](PF6)2	MUTKIV	Fe(III)2	MN3O3	[66]
[Cu2(µ2–N2A–O,O′)4(DMSO)2]·2(HN2A)·2DMSO	IXAFOC	Cu(II)2	MO5	[67]
[Cu2(µ2–N2A–O,O′)4(DMF)2]	LANDUB	Cu(II)2	MO5	[68]
[Cu2(μ2–NAP–O,O′)4(3pic)2]	RANHIA	Cu(II)2	MNO4	[48]
[Cu2(μ2–NAP–O,O′)4(caf)2]	XIRCOQ	Cu(II)2	MNO4	[69]
[Zn2(µ2–OH)(µ2–N2A–O,O′)2(TACN–Me3)2](ClO4)	MUTKOB	Zn(II)2	MN3O3	[66]
[Zn2(µ2–N2A–O,O′)4(phdat)2]	TEWNEQ	Zn(II)2	MNO4	[70]
[Ru2(µ2–N2A–O,O′)4(H2O)2](PF6)·THF	YISFIR	Ru(II)/Ru(III)	MO5	[71]
[Ru2(µ2–N1A–O,O′)4(THF)2](PF6)·THF	YISFUD	Ru(II)/Ru(III)	MO5	[71]
K[Ru2(µ2–N2A–O,O′)2(dhpta)]	KEJKOA	Ru(III)2	MNO5	[72]
[Ru2(µ2–PYA–O,O′)2(CO)4(PPh3)2]	FIKWAZ	Ru(I)2	MC2PO2	[35]
II: Tridentate bridging (μ–O,O,O′) + bidentate bridging (μ–O,O′) + bidentate chelating (κ–O,O′)
[Y2(µ2–N1A–O,O,O′)2(µ2–N1A–O,O′)2(κ–N1A–O,O′)2(phen)2]·DMF	LULCEB	Y(III)2	MN2O7	[73]
[Pr2(µ2–N1A–O,O,O′)2(µ2–N1A–O,O′)2(κ–N1A–O,O′)2(phen)2]·DMF	SILLOP	Pr(III)2	MN2O7	[73,74]
[Nd2(µ2–N1A–O,O,O′)2(µ2–N1A–O,O′)2(κ–N1A–O,O′)2(phen)2]	JOSJUZ	Nd(III)2	MN2O7	[75]
[Sm2(µ2–N1A–O,O,O′)2(µ2–N1A–O,O′)2(κ–N1A–O,O′)2(phen)2]·DMF	TIPBEA	Sm(III)2	MN2O7	[73,76]
[Eu2(µ2–N1A–O,O,O′)2(µ2–N1A–O,O′)2(κ–N1A–O,O′)2(phen)2]·DMF	SILLIJ	Eu(III)2	MN2O7	[73,77]
[GdTb(µ2–N1A–O,O,O′)2(µ2–N1A–O,O′)2(κ–N1A–O,O′)2(phen)2]	YUNFUJ	Gd(III)Tb(III)	MN2O7	[78]
[Gd2(µ2–N1A–O,O,O′)2(µ2–N1A–O,O′)2(κ–N1A–O,O′)2(phen)2]·DMF	SILMIK	Gd(III)2	MN2O7	[73,79]
[Tb2(µ2–N1A–O,O,O′)2(µ2–N1A–O,O′)2(κ–N1A–O,O′)2(phen)2]·DMF	SILMEG	Tb(III)2	MN2O7	[73,78,80]
[Yb2(µ2–N1A–O,O,O′)2(µ2–N1A–O,O′)2(κ–N1A–O,O′)2(phen)2]·DMF	WINCIG	Yb(III)2	MN2O7	[73,81]
III: Bidentate bridging (μ–O,O′) + bidentate chelating (κ–O,O′)
[Gd2(µ2–NAP–O,O′)4(NAP–O,O′)2(phen)2]	ZURGAW	Gd(III)2	MN2O6	[82]
[Dy2(µ2–NAP–O,O′)4(NAP–O,O′)2(phen)2]	ZURFUP	Dy(III)2	MN2O6	[82]
IV: Bidentate bridging (μ–O,O) + monodentate (κ–O)
[Cu2(µ2–N1A–O,O)2(N1A–O)2(Himi)4]	WURVIQ	Cu(II)2	MN2O3	[83]
V: Tridentate bridging (μ–O,O,O′) + bidentate chelating (κ–O,O′)
[Cd2(µ2–N1A–O,O,O′)2(κ–N1A–O,O′)2(phen)2]	ZUSYUJ	Cd(II)2	MN2O4	[84]
VI: Monodentate binding, bridging from other co-ligand
[Zn2(μ–dmpz)2(Hdmpz)2(N1A–O)2]	TOGQEN	Zn(II)	MN3O	[85]

3pic = 3–picoline; caf = caffeine; DMF = N,N–dimethylformamide; DMSO = dimethylsulfoxide; Hdmpz = 3,5–dimethylpyrazole; H₅dhpta = 1,3–diamino–2–hydroxypropane–N,N,N′,N′–tetraacetic acid; Himi = imidazole; phdat = 2,4–diamine–6–phenyl–1,3,5–triazine; phen = 1,10–phenanthroline; TACN–Me₃ = 1,4,7–trimethyl–1,4,7–triazacyclononane; THF = tetrahydrofuran; Tp = hydrotrispyrazolylborate; TPA = tris(2–pyridyl)amine and tren = tris(2–aminoethyl)amine.

). Complexes of the first-row transition metal ions Fe(III), Cu(II) and Zn(II) and the second-row transition metal ions Y(III), Ru(II)/Ru(III) and Cd(II) were reported, as well as those of the lanthanide ions Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III) and Yb(III) [35,48,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85]. Most of the complexes are neutral, while a few of them are cationic and complex K[Ru₂(µ₂–N2A–O,O′)₂(dhpta)] is an anionic Ru(II) complex [72].

In all of these complexes, the 1–naphthylacetato, 2–naphthylacetato, naproxen and 1–pyreneacetato ligands are the principal bridging ligands and, in some cases, other bridging co-ligands (µ–O and µ–OH) are also present [35,48,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84]. The exception of [Zn₂(μ–dmpz)₂(Hdmpz)₂(N1A–O)₂] should be noted, where the dmpz⁻¹ (Hdmpz = 3,5–dimethylpyrazole) co-ligands have the bridging role between the two Zn(II) and the N1A⁻¹ ligands are terminal monodentate ligands [85].

Regarding the bridging mode of the concerned ligands, three different bridging cases of those shown in Figure 14C–E have been observed either alone or in combination with other κ or µ modes. The number of the oxygen atoms occupying the coordination sites is high and the coordination spheres of the metal ions is mainly completed by O–donors (oxo or hydroxo bridges or solvent ligands such as H₂O, DMF, DMSO and THF), N–donors (Figure 5, Figure 6, Figure 7, Figure 8, Figure 9, Figure 10 and Figure 11) or P–donors (PPh₃).

Concerning the coordination mode of the carboxylato ligands in these complexes, five cases/combinations have been observed (Table 2). In many of the dinuclear complexes, the carboxylato ligands are coordinated only in a µ–O,O′ mode (Figure 14D) acting as O–C–O bridges (Table 2, part I) with the number of bridges varying from one to four. In the case of four bridges, the dinuclear complexes (all reported Cu(II) complexes, i.e., [Cu₂(µ₂–N2A–O,O′)₄(DMSO)₂]·2(HN1A)·2DMSO [67], [Cu₂(µ₂–N2A–O,O′)₄(DMF)₂] [68], [Cu₂(μ₂–NAP–O,O′)₄(3pic)₂] [48] and [Cu₂(μ₂–NAP–O,O′)₄(caf)₂] [69], the Zn(II) complex [Zn₂(µ₂–N2A–O,O′)₄(phdat)₂] [70] and the mixed-valence Ru(II)/Ru(III) complexes [Ru₂(µ₂–N2A–O,O′)₄(H₂O)₂](PF₆) and [Ru₂(µ₂–N1A–O,O′)₄(THF)₂](PF₆) [71]) adopt the paddlewheel arrangement around the metal atoms (Figure 18). For the dinuclear Fe(III) complexes, an additional µ₂–O bridge was also found [65,66], while in complex [Zn₂(µ₂–OH)(µ₂–N2A–O,O′)₂(TACN–Me₃)₂](ClO₄), a hydroxo bridge was reported [66].

Another significant finding is the number of the lanthanide(III) complexes of the general formula [M₂(µ₂–N1A–O,O,O′)₂(µ₂–N1A–O,O′)₂(κ–N1A–O,O′)₂(phen)₂]·DMF [73,74,75,76,77,78,79,80,81], whereby they exhibit three different binding modes; two of the four N1A ligands are tridentate-bound forming µ₂–O,O,O′ bridges, two are bidentate in a µ₂–O,O′ bridging mode and the other two ones are in the bidentate chelating (κ–O,O′) mode (Table 2, part II) (Figure 19). For the lanthanide complexes [Gd₂(µ₂–NAP–O,O′)₄(NAP–O,O′)₂(phen)₂] and [Dy₂(µ₂–NAP–O,O′)₄(NAP–O,O′)₂(phen)₂], a combination of four µ₂–O,O′ bridging and two bidentate chelating naproxen ligands was reported [82] (Table 2, part III) (Figure 20). There are also two unique examples: (i) [Cu₂(µ₂–N1A–O,O)₂(N1A–O)₂(Himi)₄] [83] bearing a combination of two µ₂–N1A–O,O monoatomic bridges and two monodentate N1A ligands (Table 2, part IV) and (ii) [Cd₂(µ₂–N1A–O,O,O′)₂(κ–N1A–O,O′)₂(phen)₂] [84], having two tridentate µ₂–O,O,O′ bridging and two bidentate chelating N1A ligands (Table 2, part V) (Figure 20).

The coordination number of the metal ions varies from five to six in the case of the transition metal ions and from eight to nine in the case of the lanthanide ions, and the metal ions adapt the corresponding geometries.

3.4. Polynuclear Complexes

Few crystal structures of polynuclear metal complexes with 1–naphthylacetato, 2–naphthylacetato and naproxen ligands were reported in the literature with the number of the metal ions being three, four and six (

Table 3. Polynuclear complexes of 1–naphthylacetato, 2–naphthylacetato and naproxen ligands. Coordination mode of the ligands and CCDC name of the complex.

Complex	CCDC Name	Reference
[Mn3(µ3–O)(µ2–N1A–O,O′)6(py)3]	OFILAS	[86]
[Cu4(µ2–N1A–O,O′)6(µ2–N1A–O,O,O′)2(CH3CN)2]	QIJYOZ	[87]
[Cd4(µ2–N1A–O,O′)4(µ2–N1A–O,O,O′)2(N1A–O)2(µ2–H2O)2(bipy)2]	FUVZED	[84]
[(Me3Sn)4(µ2–NAP–O,O′)4]	COFTOJ	[59]
{[(n–Bu)2Sn]2(µ2–N1A–O,O′)(µ2–N1A–O,O)(µ3–O)}2	OMOLIN	[88]
[Ti6(μ3–O)2(μ2–O)2(μ3–phenyl–phosphonato)2(μ2–isopropoxo)4(isopropoxo)6(μ2–N2A–O,O′)2]	EHOGOZ	[89]
[Μn6(µ3–NAP–O,O,O′)(µ2–Hsal–O,O′)(µ2–shi–N,O)5(py)6]	NIHVEI	[90]

bipy = 2,2′–bipyridine; H₂sal = salicylic acid; H₃shi = salicylhydroxamic acid and py = pyridine.

). In all of these complexes except complex NIHVEI, these ligands have a bridging role always following the µ–O,O′ bidentate bridging motif (Table 3) [59,84,86,87,88,89], while in some cases they are found in the µ₂–O,O,O′ tridentate bridging mode and monodentate terminal fashion as in complex FUVZED [84] or in the bidentate bridging µ₂–O,O mode as in complex OMOLIN [88]. In complex [Μn₆(µ₃–NAP–O,O,O′)(µ₂–Hsal–O,O′)(µ₂–shi–N,O)₅(py)₆], the naproxen ligand is in a rather rare µ₃–O,O,O′ coordination mode (Figure 14(F)) bridging three manganese ions [90].

With the exception of [(Me₃Sn)₄(µ₂–NAP–O,O′)₄] [59] which has only naproxen bridges, the co-existence of other bridging ligands is observed and they contributed to higher than two nuclearity. Diverse bridging co-ligands in diverse modes were also reported: (i) oxo ligands bridging three metal ions (µ₃–O) as in the trinuclear mixed-valence manganese complex [Mn₃(µ₃–O)(µ₂–N1A–O,O′)₆(py)₃] [86], the tetranuclear complex {[(n–Bu)₂Sn]₂(µ₂–N1A–O,O′)(N1A–O,O′)(µ₃–O)}₂ [88] and the hexanuclear complex [Ti₆(μ₃–O)₂(μ₂–O)₂(μ₃–phenyl–phosphonato)₂(μ₂–isopropoxo)₄(isopropoxo)₆(μ₂–N2A–O,O′)₂] where it also exists in the µ₂–O mode [89], (ii) aqua ligands bridging two Cd(II) ions in [Cd₄(µ₂–N1A–O,O′)₂(µ₂–N1A–O,O,O′)₂(µ₂–H₂O)₂(N1A–O)₂(bipy)₂] (bipy = 2,2′–bipyridine) [84], (iii) μ₃–phenyl–phosphonato and (iv) μ₂–isopropoxo ligands in the hexanuclear complex EHOGOZ [89], and (v) (µ₂–Hsal–O,O′) and (vi) (µ₂–shi–N,O) ligands in the complex NIHVEI [90] (Figure 21).

Considering the structural features of these seven complexes, different arrangements of the metal ions were found resulting from differences in the nuclearity and the nature of metal ions and co-ligands. More specifically, the three manganese ions in the complex [Mn₃(µ₃–O)(µ₂–N1A–O,O′)₆(py)₃] are located in a triangular arrangement with the µ₃–O atom in the center of the triangle [86]. In the tetranuclear copper(II) complex [Cu₄(µ₂–N1A–O,O′)₆(µ₂–N1A–O,O,O′)₂(MeCN)₂], each pair of copper(II) ions adapted the paddlewheel arrangement of the type [Cu₂(µ₂–N1A–O,O′)₃(µ₂–N1A–O,O,O′)(CH₃CN)] and are joined via the two tridentate µ₂–N1A–O,O,O′ ligands providing a dimer structure of dimers [87]. The tetranuclear Cd(II) complex [Cd₄(µ₂–N1A–O,O′)₄(µ₂–N1A–O,O,O′)₂(µ₂–H₂O)₂(bipy)₂] could be described as a dimer of dimers since two µ₂–N1A–O,O′ ligands behave as bridges between the two dinuclear moieties of the type [Cd₂(µ₂–N1A–O,O′)(µ₂–N1A–O,O,O′)(µ₂–H₂O)(bipy)] [84]. [(Me₃Sn)₄(µ₂–NAP–O,O′)₄] could be characterized as a 16–metallocoronate–4 complex since a cyclic arrangement of the Sn(IV) ions bridged by the naproxen ligands was observed [59]. The arrangement of the tin ions in complex {[(n–Bu)₂Sn]₂(µ₂–N1A–O,O′)(µ₂–N1A–O,O)(µ₃–O)}₂ is circular with two µ₂–N1A–O,O′ and two µ₂–N1A–O,O bridges forming a [Sn–O–C–O–Sn–O] repeating unit which is further stabilized by two encapsulated µ₃–O atoms [88].

In the case of the hexanuclear titanium complex EHOGOZ, the structure could be described as a dimer of trimers of the type [Ti₃(μ₃–O)(μ₂–isopropoxo)₂(isopropoxo)₃(μ₂–N2A–O,O′)] which are held together by two μ₂–O and two μ₃–phenyl–phosphonato bridging ligands [89]. The hexanuclear complex [Μn₆(µ₃–NAP–O,O,O′)(µ₂–Hsal–O,O′)(µ₂–shi–N,O)₅(py)₆] is better described as a metallacrown (MC) complex Mn(II)(µ₃–NAP–O,O,O′)(µ₂–Hsal–O,O′)[15–MC_{Mn(III)N(shi)}–5](py)₆. In this complex, five Mn(III) and five triply deprotonated shi^3– bridging ligands are located in a close circular arrangement with five [Mn–N–O] repeating units forming a 15-membered MC ring of the type [15–MC–5] that can encapsulate the sixth Mn(II) ion which is further stabilized by the µ₃–naproxen–O,O,O′ and µ₂–salicylato–O,O′ bridges with the MC Mn(III) ions [90].

3.5. Polymeric Complexes

The polymeric complexes containing 1–naphthylacetato and naproxen ligands are summarized in

Table 4. Polymeric complexes of 1–naphthylacetato and naproxen ligands. Coordination mode of the ligands, CCDC name of the complex and polymerization linkers.

Complex	CCDC Name	Polymerized via	Reference
Part I: As bridging ligands
[Mg(µ2–NAP–O,O)(µ2–NAP–O,O′)(µ2–H2O)]n	ANOMEW	µ2–O,O, µ2–O,O′, µ2–H2O	[41]
[Mn(µ2–NAP–O,O′)2(CH3OH)]n	NIHVOS	µ2–O,O′	[90]
[Co(µ2–N1A–O,O′)2(H2O)2]n	MEQHAS	µ2–O,O′	[91,92]
[Cd(NAP–O,O′)(µ2–NAP–O,O,O′)(H2O)]n	ZASZIE	µ2–O,O,O′	[46]
[(Ph3Sn)(µ2–NAP–O,O′)]n	COFTID	µ2–O,O′	[59]
[(n–Bu)3Sn(µ2–N1A–O,O,O′)]n	OMOLOT	µ2–O,O,O′	[88]
[Ag4(µ2–NAP–O,O′)2(µ3–NAP–O,O,O′)2(2pic)2]n	CAVHOA	µ2–O,O,O′	[93]
Part II: As coordinated ligands, other bridges
[Zn(NAP–O)2(µ–3U)]n	OMALIA	3U	[94]
[Zn(NAP–O)2(µ–4U)]n	OMALEW	4U	[94]
[Cd3(µ2–N1A–O,O′)2(µ2–N1A–O,O,O′)2(µ2–4,4′–bipy)2(κ–N1A–O,O′)2]n	FUVZIH	4,4′–bipy	[84]
[Cd(µ3–pyr3O)(N1A–O,O′)(H2O)]n,	MIRSAI	pyr3O	[84]
[Ag(N1A–O)(µ–bpp–N,N′)]n	VIGDIA	bpp	[95]

2pic = 2–picoline; 3U = 1,3–dipyridin–3–ylurea; 4U = 1,3–dipyridin–4–ylurea; 4,4′–bipy = 4,4′–bipyridine; bpp = 1,3–bis(4–pyridyl)propane and pyr3OH = pyridin–3–ol.

and may be categorized in two groups: (I) the polymeric complexes that are polymerized via the 1–naphthylacetato and naproxen ligands [41,46,59,88,90,91,92,93] (Table 4, part I), Figure 22) and (II) the polymeric complexes that are polymerized via other co-ligands, and the 1–naphthylacetato and naproxen ligands are just found in the coordination sphere [84,94,95] (Table 4, part II). Most of the reported polymeric complexes bear a monomeric complex as the basis of the polymer with the exception of complexes FUVZIH and CAVHOA which have a trinuclear Cd(II) and a tetranuclear Ag(I) complex, respectively, as the repeating unit of the polymeric structure.

In the first group of the complexes, where the 1–naphthylacetato and naproxen ligands are the polymerizing linkers (Table 4, part I), the ligands are in either bidentate µ₂–O,O′ or tridentate µ₂–O,O,O′ bridging modes. Only in the case of complex [Mg(µ₂–NAP–O,O)(µ₂–NAP–O,O′)(µ₂–H₂O)]_n, three different linkers were found, i.e., bidentate µ₂–NAP–O,O, bidentate µ₂–NAP–O,O′ and µ₂–H₂O [41]. Besides the role of the polymerizing linker, there is a bidentate chelating naproxen ligand in complex [Cd(NAP–O,O′)(µ₂–NAP–O,O,O′)(H₂O)]_n [46] and two bidentate µ₂–O,O′ naproxen ligands which are forming bridges between the Ag(I) of the repeating tetranuclear unit in complex CAVHOA [93].

In the second group of the complexes, i.e., complexes polymerized via the other co–ligands (Table 4, part II), the 1–naphthylacetato and naproxen ligands are bound in the central metal ion either monodentately as in complexes [Zn(NAP–O)₂(µ–3U)]_n and [Zn(NAP–O)₂(µ–4U)]_n [94] and [Ag(N1A–O)(µ–bpp–N,N′)]_n [84] or in a bidentate chelating mode as in complex [Cd(µ₃–pyr3O)(N1A–O,O′)(H₂O)]_n [95]. The polymerization in these complexes takes place via the 1,3–dipyridin–3–ylurea, 1,3–dipyridin–4–ylurea, pyridin–3–ol and 1,3–bis(4–pyridyl)propane ligands, respectively. In the case of complex FUVZIH, the basic unit is a trinuclear Cd(II) complex where every two of the six 1–naphthylacetato ligands are found in three different binding modes in the trinuclear complex (µ₂–N1A–O,O′, µ₂–N1A–O,O,O′ and κ–N1A–O,O′), while the polymerization takes place via the 4,4′–bipyridine ligands [84].

4. Spectroscopic and Physicochemical Characterization of the Metal Complexes

Besides the X-ray crystal structures, the reported metal complexes were also studied and characterized using various (spectroscopic and physicochemical) techniques, and their use mainly depended on the nature of the metal ion. The most often reported spectroscopic techniques are IR, NMR, photochemical (UV–vis, fluorescence), EPR and Mössbauer spectroscopies. Other techniques employed for the characterization of the complexes include thermal analysis, magnetic measurements and electrochemistry.

4.1. IR Spectroscopy

In most cases, the IR spectra of the reported complexes were discussed as a preliminary method to assess the presence, the deprotonation and the possible coordination mode of the carboxylato ligands. In the IR spectra of the complexes, two characteristic bands of the carboxylato ligands were observed: the band located in the range 1530–1645 cm⁻¹ was attributed to the antisymmetric stretching vibration (ν_asym(COO)) of the deprotonated carboxylato group, while the second band located in the region 1370–1480 cm⁻¹ was assigned to the symmetric stretching vibration (ν_sym(COO)) of the deprotonated carboxylato group (Table S1). Their difference (= ν_asym(COO) − ν_sym(COO)) is known as the parameter Δν(COO) and is often used to estimate the potential coordination mode of carboxylato ligands [96]. The Δν(COO) value of each complex is compared with that of the deprotonated carboxylato ligand (usually in the form of an alkali salt) and may suggest (i) a monodentate (asymmetric) coordination, if Δν(COO)_complex > Δν(COO)_salt or (ii) a bidentate binding mode when Δν(COO)_complex < Δν(COO)_salt [97]. The limits of these values often depend on the nature of the metal ion. In addition, in the case of more than one coordination mode of the ligands (e.g., monodentate and bidentate bridging), two values for Δν(COO) may be observed. In most cases, characteristic bands concerning the presence of the corresponding co-ligands, e.g., the out-of-plane ρ(C–H) vibrations of the respective nitrogen–donor co-ligands, have also been observed and reported [42,43,47,48,49,50,56,59,60,61,63,71,73,75,90,93].

4.2. NMR Spectroscopy

NMR spectroscopy was mainly applied to diamagnetic complexes, i.e., Zn(II), Ag(I) and Sn(IV) complexes. In most cases, the ¹H and ¹³C NMR spectra were recorded in solutions of the complexes. In the reported ¹H and ¹³C NMR spectra of Ag(I) [50,93], Zn(II) [63] and Sn(IV) [59] with NAP ligands and of complex [Ru₂(µ₂–PYA–O,O′)₂(CO)₄(PPh₃)₂] [35], all of the expected signals of the NAP or PYA ligands and the respective co-ligands were present and slightly shifted downfield or upfield (compared with free HNAP or HPYA) as a result of their coordination to the metal ions. In general, the results were in good agreement with the determined crystal structures and proposed structures of the complexes. The absence of any additional signals related to other species revealed the stability of the complexes in solution.

In few cases, the ³¹P or ¹¹⁹Sn NMR spectra were also recorded for complexes bearing P–donor co-ligands or for tin complexes, respectively. In particular, the ³¹P{¹H} NMR spectrum of [Ru₂(µ₂–PYA–O,O′)₂(CO)₄(PPh₃)₂] showed a signal characteristic for the PPh₃ axial ligands [35]. Especially for the Sn(IV) complexes [59], the ¹¹⁹Sn NMR spectra were also recorded and gave significant information regarding the environment of Sn(IV) ions. Based on the values of the ¹¹⁹Sn NMR chemical shifts (and according to the related literature [98]), penta-coordination of Sn was suggested for five complexes (δ = −190 to −90 ppm), i.e., ([(Me₃Sn)₄(NAP)₄], [((n–Bu)₃Sn)₄(NAP)₄], [(Ph₃Sn)(NAP)]_n, [((PhCH₂)₃Sn)(NAP)]_n and {[Me₂Sn(NAP)]₂O}₂, and the hexa-coordination of Sn was proposed for three complexes (for δ values in the range from −400 to −210 ppm), namely [((n–Bu)₂Sn)(NAP)₂], [(Ph₂Sn)(NAP)₂] and [((PhCH₂)₂Sn)(NAP)₂]; these conclusions were also confirmed by the reported X-ray crystal structures [59].

4.3. Photochemical Properties

In order to study the photochemical behavior of the reported complexes, their electronic (UV–vis) and fluorescence spectra were recorded.

The UV–vis spectra of the transition metal complexes were recorded in solution and in solid state and were used to check whether the complexes retained their stability in solution and across time. In most of the reported cases, the discussion was focused on the visible area of the spectrum in order to characterize the bands assigned to d–d transitions of the centered metal ions.

For Co(II)–naproxen complexes, the bands assigned to ⁴Τ_1g(F) → ⁴T_2g, ⁴Τ_2g(F) → ⁴A_2g and ⁴Τ_1g(F) → ⁴T_1g(P) transitions were found in the ranges 735–740 nm, 535–570 nm and 445–450 nm, respectively [43]. For the Ni(II)–naproxen complexes, the bands attributed to the ³A_2g → ³T_2g, ³A_2g → ³T_1g and ³A_2g → ³T_1g(P) transitions were observed in the regions 930–1015 nm, 520–730 nm and 390–403 nm, respectively [61]. For mixed-valence manganese(II/III) complexes, the d–d transition band related to Mn(III) ions was observed at 620–635 nm [90]. For Fe(III) complexes, the band related to the d–d transitions of Fe(III) ions was found at 700–730 nm [65,66]. In the case of Cu(II) complexes, the d–d transition band of Cu(II) ions was found in the range 612–730 nm [49,56], which is dependent on the geometry of the coordination sphere around copper(II) ions [99].

Considering the photoluminescence properties of the reported complexes, the fluorescence emission spectra of complexes containing either d¹⁰ metal ions (i.e., Zn(II) and Cd(II)) or lanthanide(III) ions were recorded with diverse excitation wavelengths.

The emission bands recorded for complexes [Zn(NAP)₂(H₂O)₂], [Cd(NAP)₂(H₂O)₂] and [Cd(NAP)₂(H₂O)]_n at 360 nm (λ_excitation = 300 nm), 356 nm (λ_excitation = 280 nm) and 355 nm (λ_excitation = 280 nm), respectively, were assigned to intraligand (π–π*) fluorescence emissions, as the spectra of free HNAP presented emission bands at 347 nm and 372 nm (for λ_ex = 280 nm) [46]. Similarly, the emission bands of complexes [Cd₂(N1A)₄(phen)₂] (λ_max,emission = 421 nm and ~575 nm for λ_excitation = 370 nm), [Cd₄(N1A)₈(bipy)₂(H₂O)₂] (λ_max,emission = 421 nm for λ_ex = 370 nm), [Cd₃(N1A)₆(4,4′–bipy)₂]_n (λ_max,emission = 421 nm and ~570 nm for λ_excitation = 345 nm) [84] and [Zn₂(N2A)₄(phdat)₂] (λ_max,emission = 404 nm for λ_excitation = 304 nm) [70] were assigned to the intraligand π–π* transition of coordinated 1–naphthylacetato [84] or 2–naphthylacetato ligands [70] (λ_max,emission = 420 nm for λ_excitation = 345 nm). For the lanthanide(III) complexes, a series of emission bands were observed in the region 540–700 nm and were mainly assigned to the f–f transitions of the respective lanthanide(III) ions (

Table 5. Luminescence data for reported complexes.

Complex	λexcitation (nm)	λmax,emission (nm) (Transition)	Reference
[Eu2(N1A)6(phen)2]·2DMF	322	581 (5D0→7F0), 593 (5D0→F1), 618 (5D0→7F2), 651 (5D0→7F3), 694 (5D0→7F4)	[73]
[Sm2(N1A)6(phen)2]·2DMF	335	566 (4G5/2→6H5/2), 594 (4G5/2→6H7/2), 617 (4G5/2→6H7/2), 648 (4G5/2→6H9/2), 680 (4G5/2→6H11/2)	[73]
[Tb2(N1A)6(phen)2]·2DMF	345	545 (5D4→7F5), 594 (5D4→7F4), 617 (5D4→7F3), 675 (5D4→7F2)	[73]
[Eu(N1A)2(phen)2(H2O)2](N1A)2·2H2O	332	580 (5D0→7F0), 592 (5D0→7F1), 617 (5D0→7F2), 674 (5D0→7F3), 697 (5D0→7F4)	[52]
[Gd2(N1A)6(phen)2]	351	490 (5D4→7F6), 593 (5D4→7F4), 615 (5D4→7F3), 645 (5D4→7F2)	[78]
[Tb2(N1A)6(phen)2].DMF	359	490 (5D4→7F5), 594 (5D4→7F4), 615 (5D4→7F3)	[78]

DMF = N,N-dimethylformamide; phen = 1,10-phenanthroline.

) [52,73,78].

In addition, the static emission spectra of 1–naphthylacetic acid, 2–naphthylacetic acid and their Ru(III) and Mn(II/III) complexes were also reported. The Ru(III) complexes K[Ru₂(N1A)₂(dhpta)] and K[Ru₂(N2A)₂(dhpta)] exhibited fluorescence and phosphorescence in the regions 300–400 nm and 400–550 nm, respectively, when excited at 295 nm, and showed very short fluorescence lifetimes (36 ps and 540 fs, respectively) [72]. Complexes [Mn₃(µ₃–O)(µ₂–N1A–O,O′)₆(py)₃] and [Mn₃(µ₃–O)(µ₂–N2A–O,O′)₆(py)₃] showed fluorescence with higher fluorescence lifetimes (in the range 13–48 ns, depending on the solvent used) [86].

4.4. EPR Spectroscopy

EPR spectra were recorded for few Cu(II) and Co(II) naproxen complexes in powder samples as well as in frozen solution. In general, a comparison of the EPR spectra between powder samples and solutions was useful to reveal that the complexes retained their structure in solution.

The EPR spectra of powder samples of [Cu(NAP)₂(bipy)] and [Cu(NAP)₂(phen)] [56] and [Cu(NAP)(L1–L6)Cl] [49] showed signals with g_|| > g_⊥ > 2 which are close to the expected values for distorted octahedral geometry around Cu(II) ions [100]. Furthermore, the EPR spectrum of the DMSO solution of [Cu(NAP)₂(bipy)] was similar to the powder sample verifying the geometry around Cu(II) ions, and the hyperfine pattern was resolved and gave the following: A_|| = 400 MHz, A_⊥ = 20 MHz, g_⊥ = 2.06 and g_|| = 2.26 [56]. The EPR spectrum of the dinuclear complex [Cu₂(NAP)₄(caf)₂] was similar to other symmetric dimeric copper(II) species with g_⊥ = 2.04 and g_|| = 2.23 [69].

The EPR spectra of complex [Co(NAP)₂(py)₂(H₂O)₂] were recorded in frozen DMSO solution and in powder samples which showed similar signals (a derivative centered at g = 4.8 and a broad peak at g =1.9) at low temperatures (T < 25 K) [43], typical for high-spin Co(II) ions.

4.5. Mössbauer Spectroscopy

Mössbauer spectroscopy was involved in the characterization of one Sn(IV) complex. More specifically, the ¹¹⁹Sn Mössbauer spectrum of [(n–Bu)₂Sn(NAP–O,O′)₂] was recorded in solid state and it was typical for Sn complexes. The isomer shift (δ) value (1.40 mm s⁻¹) showed the oxidation state of Sn(IV) and the value of the quadrupole splitting parameter (D) was 3.44 mm s⁻¹, being typical for trans-R₂Sn distorted octahedral complexes [60].

4.6. Thermal Behavior

The thermal behavior and stability of reported Cu(II), Zn(II), Ag(I) and Cd(II) complexes were mainly examined using thermogravimetric analysis (TGA) and differential thermogravimetric analysis (DTA). In addition, the decomposition steps were also investigated. The reported complexes were stable up to temperatures varying between 122 and 294 °C and this was followed by their decomposition up to three steps (

Table 6. Data regarding the thermal behavior and stability of reported complexes.

Compounds	Stable Until (°C)	Steps	Temperature per Step	Reference
[Cu2(NAP)4(3pic)2]	161	two	I: 130–177 II: 177–455	[48]
[Cu(NAP)2(H2O)(4pic)2]	122	two	I: 30–173 II: 173–461	[48]
[Cu4(N1A)8(CH3CN)2]	175.7	three	I: 175.7–185.2 II: 252.8–266.9 III: 493.8–587.5	[87]
[Cu(N1A)(EDA)2](ClO4)	Not given	two	I: 162–355 II: 355–616	[47]
[Cu(N1A)2(Hdmpz)2]	180	two	I: 188.4–270.4 II: 290.7–433.1	[45]
[Zn2(dmpz)2(Hdmpz)2(N1A)2]	180	three	I: 188.4–282.8 II: 285.4–422.6 III: 437.7–606.4	[85]
[Zn2(N2A)4(phdat)2]	208	three	I + II + III: 208–586	[70]
[Ag4(NAP)4(2pic)2]n	Not given	two	I: 30–204 II: 204–557	[93]
[Cd2(N1A)4(phen)2]	267	two	I + II: 267–483	[84]
[Cd4(N1A)8(bipy)2(H2O)2]	130	two	I: 130–190 II: 230–452	[84]
[Cd3(N1A)6(4,4′–bipy)2]n	294	one	294–449	[84]

2pic = 2–picoline; 3pic = 3–picoline; 4pic = 4–picoline; 4,4′–bipy = 4,4′–bipyridine; bipy = 2,2′–bipyridine; EDA = N,N–dimethylethane–1,2–diamine; Hdmpz = 3,5–dimethylpyrazole; phdat = 2,4–diamine–6–phenyl–1,3,5–triazine and phen = 1,10–phenanthroline.

). During these steps, the gradual loss of the ligands took place resulting in the formation of the corresponding metal oxide as the final product. In most cases, the mass losses found experimentally from the respective thermogravimetric curves were in good agreement with the theoretically calculated mass losses [45,47,48,70,84,85,87,93].

4.7. Magnetic Measurements

The magnetic properties of the paramagnetic metal complexes were often studied and reported. In most cases, especially for the mononuclear complexes, room-temperature (RT) magnetic measurements were adequate to prove their monomeric nature. For the mononuclear Co(II), Ni(II) and Cu(II) complexes as well as the dinuclear Cu(II) complexes bearing a paddlewheel arrangement of the ligands, the observed μ_eff values at RT were close to the spin-only (theoretically expected) values and further variable temperature (VT) magnetic measurements were not conducted [43,49,56,61,69].

VΤ magnetic measurement studies were performed for a series of polynuclear manganese(II/III), iron(III), copper(II), ruthenium(III) and lanthanide(III) complexes with 1–naphthylacetato and 2–naphthylacetato ligands. For all of the reported Mn(II/III), Fe(III), Cu(II) and Ru(III) complexes, the molecular susceptibility χ_M decreased upon lowering the temperature and below a temperature it increased up to a plateau value. This behavior is typical for antiferromagnetic interactions between the metal ions. The data were further fitted with appropriate equations and the corresponding g and J parameters were calculated as cited in

Table 7. Magnetic parameters derived from the fitting to temperature-dependent molar susceptibility of reported complexes.

Complex	J (cm−1)	g	Reference
[Mn3(µ3–O)(µ2–N1A–O,O′)6(py)3]	−7.5 a, −5.0 b	2.06	[86]
[Mn3(µ3–O)(µ2–N2A–O,O′)6(py)3]	−7.0 a, −4.9 b	2.06	[86]
[Fe2(µ2–O)(µ2–N2A–O,O′)2(TACN–Me3)2](PF6)2	−105		[66]
[Fe2(µ2–O)(µ2–N2A–O,O′)(tren)2](BPh4)(NO3)2 [Fe2(µ2–O)(µ2–N2A–O,O′)(TPA)2](ClO4)3 [Fe2(µ2–O)(µ2–N2A–O,O′)2(Tp)2]	−130 ± 10		[66]
[Cu4(N1A)8(CH3CN)]	2J1 = −295 c, 2J2 = −38 c	2.28	[87]
K[Ru2(µ2–N1A–O,O′)2(dhpta)]	−581	2.1	[72]
K[Ru2(µ2–N2A–O,O′)2(dhpta)]	−378	2.1	[72]

H₅dhpta = 1,3–diamino–2–hydroxypropane–N,N,N′,N′–tetraacetic acid; py = pyridine; TACN–Me₃ = 1,4,7–trimethyl–1,4,7–triazacyclononane; Tp^– = hydrotrispyrazolylborate; TPA = tris(2–pyridyl)amine and tren = tris(2–aminoethyl)amine. ^a Value of the Mn(II)–Mn(III) interaction. ^b Value of the Mn(III)–Mn(III) interaction. ^c Value for different Cu(II)–Cu(II) interactions.

. In all cases, the calculated parameters were in good agreement with previously reported data concerning complexes with similar structural motifs [65,66,72,86,87]. On the other hand, the VT magnetic behavior of the three lanthanide(III) complexes [Ln₂(µ₂–NAP–O,O′)₄(NAP–O,O′)₂(phen)₂] (Ln = Dy, Gd and Er) may be attributed to a single-molecule magnet (SMM) behavior [82].

4.8. Electrochemical Behavior

In order to study the electrochemical behavior of the complexes, the cyclic voltammograms of the complexes were recorded in solution. More specifically, the cyclic voltammograms of Mn(II/III) [86], Fe(III) [65,66] and Ru(III) [72] with 1–naphthylacetato and 2–naphthylacetato ligands and Co(II) [43], Ni(II) [61] and Cu(II) [49,55] complexes with naproxen ligands were recorded in diverse solvents and the redox potentials of the observed waves were studied.

In the case of the polynuclear complexes bearing 1–naphthylacetato or 2–naphthylacetato ligands, two distinct processes were observed: (i) the reduction and oxidation of the naphthalene moiety took place at extreme potentials providing rather quasi-reversible waves (E_pc < −1.5 V, E_pa > +1.0 V), while (ii) the metal-centered redox processes (M(II) ↔ M(III)) were observed at rather close-to-zero potentials resulting in quasi-reversible or irreversible waves (

Table 8. Redox potentials (in V) and process for complexes bearing 1–naphthylacetato or 2–naphthylacetato ligands.

Complex		Naphthalene Moiety		Metal-Centered		Reference
	Solvent	Reduction (Epc)	Oxidation (Epa)	Reduction (Epc)	Oxidation (Epa)
[Fe2O(N2A)(tren)2](BPh4)(NO3)2	CH3CN	−1.78	+1.46	−0.60 a		[65]
[Fe2O(N2A)(TPA)2](ClO4)3	CH3CN	−2.20, −2.40	+1.50	−1.20 a	+0.83 b	[65]
[Fe2O(N2A)2(Tp)2]	CH3CN	−2.05	+1.60	−1.07 a	+1.30 b	[65]
[Fe2O(N2A)2(TACN–Me3)2](PF6)2	CH3CN	−1.9	+1.65	−0.75 a,c		[66]
[Mn3O(N1A)6(py)3]	CH2Cl2		+1.05	−0.70 c,e	0.02 c,d −0.61	[86]
[Mn3O(N2A)6(py)3]	CH2Cl2		+1.03	−0.61 c,e	0.09 c,d −0.57 c,d	[86]
K[Ru2(N1A)2(dhpta)]	CH3CN DMF		+1.29	−1.05 f, −1.36 g −1.27 f, −1.73 g	0.63 c,h 0.53 c,h	[72]
K[Ru2(N2A)2(dhpta)]	CH3CN DMF		+1.30	−1.05 f, −1.34 g −1.28 f, −1.71 g	0.64 c,f 0.54 c,f	[72]

H₅dhpta = 1,3–diamino–2–hydroxypropane–N,N,N′,N′–tetraacetic acid; py = pyridine; TACN–Me₃ = 1,4,7–trimethyl–1,4,7–triazacyclononane; Tp⁻ = hydrotrispyrazolylborate; TPA = tris(2–pyridyl)amine and tren = tris(2–aminoethyl)amine. ^a [Fe(III)] → [Fe(II)] process. ^b [Fe(II)] → [Fe(III)] process. ^c provided value for E_1/2. ^d [Mn(II)] → [Mn(III)]. ^e [Mn(III)] → [Mn(II)]. ^f [Ru(III)Ru(III)] → [Ru(II)Ru(III)]. ^g [Ru(II)Ru(III)] → [Ru(II)Ru(II)]. ^h [Ru(III)Ru(III)] → [Ru(IV)Ru(III)].

).

In the cases of the mononuclear metal(II)-naproxen complexes, irreversible or quasi-reversible waves attributed to one-electron processes were observed. In all cases, the redox process [M(II)] ↔ [M(I)] was successfully assigned to E_pc and E_pa at potentials depending on the nature of metal ions (

Table 9. Cathodic and anodic potentials (in mV) for the redox couples [M(II)]/[M(I)] (M = Co, Ni and Cu) (E_pc1, E_pa1) for complexes bearing naproxen ligands.

Complex	Epc a	Epa b	Reference
[Co(NAP)2(MeOH)4]	–1109 a	–13 b	[43]
[Co(NAP)2(py)2(H2O)2]	–775	–25 b	[43]
[Co(NAP)2(phen)(H2O)2]	–1296	+53 b	[43]
[Co(NAP)2(bipy)(H2O)2]	–1065	–56 b	[43]
[Ni(NAP)2(MeOH)4]	–607	–384	[61]
[Ni(NAP)2(bipy)(CH3OH)]	–544	–304	[61]
[Ni(NAP)2(phen)(H2O)]	–485	–307	[61]
[Ni(NAP)2(bipyam)]	–531	–314	[61]
[Ni(NAP)2(Hpko)2]	–473	–362	[61]
[Ni(NAP)2(py)2(H2O)2]	–524	–314	[61]
[Cu(NAP)2(4,7–dphphen)]	–355	Not provided	[55]

4,7–diPhphen = 4,7–diphenyl–1,10–phenanthroline; bipy = 2,2′–bipyridine; bipyam = 2,2′–bipyridylamine; Hpko = di(2–pyridyl)ketone oxime; phen = 1,10–phenanthroline and py = pyridine. ^a E_pc refers to [M(II)] → [M(I)] process. ^b E_pa refers to [M(I)] → [M(II)] process.

) [43,55,61].

Furthermore, five metal(II)–naproxen complexes (namely [Ni(H₂O)₆](NAP)₂·2H₂O, [Cu(NAP)₂(H₂O)₃]·H₂O, [Zn(NAP)₂(H₂O)₂]·H₂O, [Cd(NAP)₂(H₂O)₂]·H₂O and [Cd(NAP)₂(H₂O)]_n were checked for potential ferroelectric properties, since they crystallized in polar space groups which is a condition for ferroelectricity [46]. The properties examined for these complexes were remnant polarization (P_r) (with values of 0.004–0.022 µC/cm²), coercive field (E_c) (values of 0.077–1.04 kV/cm) and saturation spontaneous polarization (P_s) (in the range of 0.006–0.046 µC/cm²); in combination with the low leakage currents (<10⁻⁸ A/cm²), these may confirm the ferroelectricity of the complexes.

5. Biological Activity

Many of the reported coordination compounds were screened in vitro for their potential biological activity. Therefore, the potential anticancer activity of selected complexes was monitored by determining their cytotoxicity against diverse cancer cell lines. The antibacterial activity of many complexes was tested against diverse microorganisms. The antioxidant capacity of many naproxen complexes was investigated against free radicals and via the inhibition of relevant enzymes. Few reports were found concerning other activities such as catechol oxidase-like activity and antimalarial activity. Complimentary to these studies, the interaction and the affinity of the reported complexes for certain biomacromolecules, i.e., DNA and albumins, were also evaluated in vitro.

5.1. Anticancer Activity of the Complexes

In order to evaluate the potential anticancer potency of the reported compounds, their cytotoxic efficacy was monitored in vitro against the following cancer cell lines: 4T1 (human breast cancer), A–549 (human lung carcinoma), Colo205 (human adenocarcinoma), HEK–293 (human embryonic kidney), HeLa (cervical cancer), HepG2 (human hepatoblastoma), HT–29 (human colorectal adenocarcinoma), MCF–7 (breast cancer), MDA–MB–231 (human breast cancer), MDA–MB–453 (human breast adenocarcinoma), MDA–MB–468 (human breast cancer), NCI–H460 (human large-cell lung carcinoma), HMLER cells (immortalized and transformed via retroviral expression of SV40 large T oncogene, hTERT and HrasV12) and HMLER–shEcad cells (HMLER cells subjected to Ecadherin silencing by short hairpin RNA interference), as well as against the 3T3–L1 normal cells from mouse fibroblasts. The cytotoxicity of the complexes was evaluated in comparison to their corresponding ligands and diverse reference compounds including 5–fluorouracil, capecitabin, carboplatin, cisplatin, doxorubicin and salinomycin.

The results were expressed as the concentration that inhibits the survival of 50% of the cells (IC₅₀, in μM). The reported complexes (

Table 10. In vitro cytotoxicity of reported compounds (IC₅₀, in μM) against diverse cancer cell lines and normal cells (3T3–L1) after treatment for 48 h.

Compound	Cell Lines		Reference
HNAP	MCF–7: >160 HeLa: >160 3T3–L1: >250	A549: >160 MDA–MB–453: >100 HT–29: >100	[49,90,93]
[Μn6(NAP)(Hsal)(shi)6(py)6]	MCF–7: 9.6 ± 0.3 HeLa: 30.1 ± 1.3	A549: 69.3 ± 4.0	[90]
[Μn(NAP)2(CH3OH)]n	MCF–7: 62.0 ± 2.5 HeLa: >160	A549: >160	[90]
[Cu(NAP)(L1)Cl]	MCF–7: 1.51 ± 0.15		[49]
[Cu(NAP)(L2)Cl]	MCF–7: 31.03 ± 1.2		[49]
[Cu(NAP)(L3)Cl]	MCF–7: 10.40 ± 0.3		[49]
[Ag4(NAP)4(2pic)2]n	A549: 74.08 ± 1.05 3T3–L1: 224.87 ± 2.60	MDA–MB–453: 39.77 ± 1.95 HT–29: 29.96 ± 0.84	[49]
[Ag(NAP)(PPh3)3](H2O)	MCF–7: 0.7 ± 0.1		[50]
[Ag(NAP)(tptp)2]	MCF–7: 2.2 ± 0.2		[50]
[Ni(NAP)2(phen)(H2O)]	HepG2: >1000 HT 29: 35.50  ±  1.94	HEK–293: 198.5  ±  35.45 (72h)	[62]
[Co(NAP)2(cyclam)]	HMLER: 0.43 ± 0.05	HMLER–shEcad: 0.11 ± 0.03	[44]
[Au(NAP)(PPh3)]	HMLER: 0.183 ± 0.001 MDA–MB–231: 7.77 ± 0.41 4T1: 10.08 ± 0.86	HMLER–shEcad: 0.063 ± 0.006 MDA–MB–468: 6.48 ± 1.43	[51]
{[(n–Bu)2Sn]2(N1A)2(O)}2	MCF–7: 37.61 HeLa: 1.805 HepG2: 0.802	Colo205: 0.100 NCI–H460: 67.29	[88]
[(n–Bu)3Sn(N1A)]n	MCF–7: 0.301 HeLa: 0.361 HepG2: 0.127	Colo205: 0.104 NCI–H460: 0.188	[88]
H3shi	MCF–7: >160 HeLa: >160	A549: >160	[90]
PPh3	MCF–7: 67.4 ± 13.9		[50]
tptp	MCF–7: 26.5 ± 2.8		[50]
5–Fluorouracil	HMLER: 41.05 ± 5.30	HMLER–shEcad: 49.10 ± 5.94	[51]
Capecitabin	HMLER: >100	HMLER–shEcad: >100	[51]
Carboplatin	MCF–7: 26.83 HepG2: 0.613 A549: 39.43 ± 0.76 NCI–H460: 62.13 HT–29: 47.15 ± 2.80 HMLER: 67.31 ± 2.80	HeLa: 24.78 Colo205: 0.531 MDA–MB–453: 56.73 ± 1.24 HMLER–shEcad: 72.39± 7.99 3T3–L1: 43.20 ± 1.35	[3,51,88]
Cisplatin	MCF–7: 8.0 ± 0.7 HepG2: 23.71  ±  1.52 HT 29: 69.13  ±  1.88	HEK–293: 46.81 ± 2.79 HMLER–shEcad: 5.64 ± 0.30 HMLER: 2.56 ± 0.02	[49,50,51,62]
Doxorubicin	MCF–7: 10.90		[49]
Salinomycin	HMLER: 11.43 ± 0.42	HMLER–shEcad: 4.23 ± 0.35	[44,51]

2pic = 2–picoline; cyclam = 1,4,8,11–tetraazacyclotetradecane; H₂sal = salicylic acid; H₃shi = salicylhydroxamic acid; L1 = 4′–(4–tolyl)–2,2′:6′,2″–terpyridine; L2 = 4′–(furan–2–yl)–2,2′:6′,2″–terpyridine; L3 = 4′–(pyridin–3–yl)–2,2′:6′,2″–terpyridine; n–Bu = n–butyl; PPh₃ = triphenylphosphine; py = pyridine and tptp = tri(p–tolyl)phosphine.

) were more active than their components and in most cases were even more active than some of the reference compounds used [44,49,50,51,62,88,90,93], which launched more elaborate studies regarding the mechanism of cancer cell death. Among the tested complexes, the most active ones were found: (i) [Μn₆(NAP)(Hsal)(shi)₆(py)₆] (IC₅₀ = 9.6 ± 0.3 μM) [90], [Cu(NAP)(L1)Cl] (IC₅₀ = 1.51 ± 0.15 μM) [49], [Ag(NAP)(tptp)₂] (IC₅₀ = 2.2 ± 0.2 μM) and [Ag(NAP)(PPh₃)₃](H₂O) (IC₅₀ = 0.7 ± 0.1 μM) [50] against MCF–7 cells, (ii) [Co(NAP)₂(cyclam)] [44] and [Au(NAP–O)(PPh₃)] [51] against HMLER cells (IC₅₀ = 0.183–0.43 μM) and HMLER–shEcad cells (IC₅₀ = 0.063–0.11 μM) and (iii) {[(n–Bu)₂Sn]₂(N1A)₂(O)}₂ against HeLa, HepG2 and Colo205 cells (IC₅₀ = 0.100–1.805 μM) [88] and the polymeric complex [(n–Bu)₃Sn(N1A)]_n against all cell lines tested (IC₅₀ = 0.104–0.361 μM) [88].

More elaborate studies concerning the potential anticancer activity of the aforementioned compounds were also conducted leading to noteworthy results. In vitro experiments concerning the combinatory activity of [Μn₆(NAP)(Hsal)(shi)₆(py)₆] with the well-known chemotherapeutic drugs irinotecan, cisplatin, paclitaxel and 5–fluorouracil against MCF–7, A549 and HeLa cell lines have shown better cytotoxic activity of each combination checked in comparison to its free components, revealing that a combination of drugs may have superior activity [90].

The association of cytotoxic effects of several reported complexes on the cancer cell lines with apoptosis was studied using diverse techniques (e.g., cell morphology studies, DNA laddering and Annexin V–FITC/PI double staining). Complexes [Cu(NAP)(L1)Cl], [Cu(NAP)(L2)Cl] and [Cu(NAP)(L3)Cl] can initiate early apoptosis on MCF–7 cells with [Cu(NAP)(L3)Cl] being the most active complex that induced apoptosis up to 84% of the cancer cells [49]. The silver(I)–naproxen complexes [Ag(NAP)(PPh₃)₃](H₂O) and [Ag(NAP)(tptp)₂] may also induce apoptosis on MCF–7 cells as proposed by internucleosomal fragmentation studies [50]. The polymeric silver(I)–naproxen complex [Ag₄(NAP)₄(2pic)₂]_n may also trigger early apoptosis leading to increased HT–29 cell death which is associated with mitochondrial membrane destruction [93]. The cytotoxic activity of complex [Ni(NAP)₂(phen)(H₂O)] may also be attributed to apoptosis as revealed by Annexin V–FITC/PI double staining studies [62].

5.2. Antibacterial Activity of the Complexes

The potential antibacterial activity of the reported compounds was evaluated in vitro against diverse microorganisms. According to the literature [48,63,73,78,83,92], the antimicrobial activity of the compounds was tested against five Gram(−) bacteria (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Salmonella typhi), seven Gram(+) bacteria (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Listeria monocytogenes, Micrococcus luteus, Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus) and one yeast (Candida albicans). In most cases, the diameter of the inhibition zone (IZ) of the development of the microorganisms was measured for diverse concentrations of the compounds, while in fewer cases the minimum inhibitory concentration (MIC) was determined (Table S2, Supplementary Materials). In the cases of IZ measurements, a strong inhibitory effect was expected for IZ >20 mm, while IZ values in the range of 10–20 mm and <10 mm were assessed as having moderate and low antibacterial activities, respectively [83]. In the cases of MIC values, the lower the MIC values were, the better the antibacterial activity was.

In general, the antimicrobial activity of the reported Cu(II) and Zn(II) naproxen complexes was higher than free naproxen but significantly low when compared with reference compounds such as Erythromycin, Gentamycin, Vancomycin and Amphotericin B, employed in the experiments. In particular, the MIC values derived for complexes [Cu₂(NAP)₄(3pic)₂] and [Cu(NAP)₂(H₂O)(4pic)₂] were 256 μg/mL against Enterococcus faecalis and 128 μg/mL against Candida albicans, and the activity of the complexes was much lower than the respective reference compounds Vancomycin (MIC = 2 μg/mL) and Amphotericin B (MIC = 0.0625 μg/mL) [48]. For the six reported Zn(II)–naproxen complexes ([Zn₂(NAP)₄], [Zn(NAP)₂(phen)], [Zn(NAP)₂(neoc)], [Zn(NAP)₂(2ampy)₂], [Zn(NAP)₂(Himi)₂] and [Zn(NAP)₂(1,2–dmimid)₂]), the inhibition zones for treatment with 8.5 mM against diverse bacteria were much shorter (Table S2) than the reference compounds Erythromycin and Gentamycin, revealing rather low activity [63]. Similarly, the reported complexes bearing 1–naphthylacetato ligands were more active than free 1–naphthylacetic acid, but not as active as the reference compounds tested (Table S2) [73,78,83,92].

5.3. Antioxidant Activity of the Complexes

The reported coordination compounds of the NSAID naproxen were evaluated in vitro for their potential antioxidant activity. These studies included the scavenging of free radicals such as 1,1–diphenyl–picrylhydrazyl (DPPH), hydroxyl and 2,2′–azino–bis(3–ethylbenzothiazoline–6–sulfonic acid) (ABTS) radicals, the inhibition of the enzyme soybean lipoxygenase (LOX) and the mimicking of the enzyme superoxide dismutase (SOD).

Free radicals have unpaired electron(s) which may be transferred to neighboring molecules activating chain reactions with undesired effects in organisms such as inflammations or even cancer [101]. The antioxidant activity is often related with the donation of electrons in order to neutralize the radicals. Antioxidants are used to stop radical chain reactions either by scavenging free radicals or by inhibiting their production. The benefit of the antioxidants to organisms is the decrease in inflammations which are caused by radical-induced damages [101]. NSAIDs such as naproxen are compounds with inflammatory activity and may obviously act as radical scavengers contributing to antioxidant activity and probably to anticancer activity [102].

5.3.1. Scavenging of DPPH Radicals

DPPH is a stable radical used in EPR spectroscopy [103] and as a trap to inhibit and study radical-mediated reactions in the laboratory [104]. DPPH is the most common radical used to check in vitro the radical scavenging of compounds [104]. DPPH scavengers may additionally exhibit anticancer, anti-ageing and anti-inflammatory activity and could be potential agents used for the treatment of rheumatoid arthritis and inflammation [11,105].

A series of Mn(II), Co(II), Ni(II) and Cu(II) complexes of naproxen were tested for their potency to scavenge in vitro the DPPH radicals and the results were compared with the reference compounds nordihydroguairetic acid (NDGA) and butylated hydroxytoluene (BHT). All complexes were more active DPPH scavengers than the corresponding free naproxen (Table S3). The DPPH scavenging activity of the complexes was time-independent because no significant differences in the activity were observed after 20 min and 60 min of incubation (Table S3, Figure 23) [42,43,61].

In general, the extent of the DPPH scavenging of the complexes was mostly dependent on the nature of the metal ion; among the reported naproxen complexes, the Cu(II) and Co(II) complexes exhibited relatively higher activities which were in all cases significantly lower than the activities of the reference compounds BHT and NDGA (Table S3, Figure 24). The best DPPH scavenger among the reported naproxen complexes was [Co(NAP)₂(phen)(H₂O)₂] (DPPH% = 42.42 ± 0.13%) [42,43,61].

The co-ligands (i.e., their existence and their nature) do not seem to influence the activity of the complexes against DPPH radicals which are rather low. In conclusion, the DPPH scavenging activity of the reported metal–naproxen complexes is generally low or, in few cases, moderate.

5.3.2. Scavenging of Hydroxyl Radicals

Hydroxyl radicals are very active radicals and may launch successive radical reactions leading to the production of the dangerous reactive oxygen species (ROS) which may induce damages to tissues and inflammations. Therefore, they bear a significant role in radical chemistry, although they have a rather short life. However, compounds that can initially inhibit these successive ROS reactions by scavenging hydroxyl radicals may prove to be important antioxidant factors [11,106].

The ability of Mn(II), Co(II), Ni(II) and Cu(II) complexes of naproxen to scavenge hydroxyl radicals was evaluated in vitro and compared with the reference compound 6–hydroxy–2,5,7,8–tetramethylchromane–2–carboxylic acid (trolox). Almost all of the reported complexes exhibited very high hydroxyl scavenging activity which was even higher than the reference compound trolox (Figure 25 and Table S4). Most of the reported complexes were better scavengers of hydroxyl radicals than free naproxen (Figure 25) [42,43,61].

Among the complexes, those bearing nitrogen–donor co-ligands were significantly active, with the manganese(II) complexes [Mn(NAP)₂(py)₂(H₂O)₂] (OH% = 98.31 ± 0.67%) and [Mn(NAP)₂(phen)(H₂O)] (OH% = 97.42 ± 0.83%) being the most potent hydroxyl scavengers among the reported compounds. In particular, in the case of Co(II) and Ni(II) complexes, the complexes not bearing nitrogen–donor co-ligands, i.e., [Co(NAP)₂(CH₃OH)₄] (OH% = 96.75 ± 0.30%) and [Ni(NAP)₂(CH₃OH)₄] (OH% = 96.53 ± 0.32%) were also very potent [42,43,61].

5.3.3. ABTS Radical Scavenging

The cationic radical of ABTS can often react with antioxidants [107] and is used as a marker of the antioxidant capacity of foods [108] and the total antioxidant activity of radical scavengers [109]. Within context, the ability of the compounds to scavenge ABTS radicals is often determined as a supplementary experiment to hydroxyl and DPPH radicals [11] and is compared with the reference compound trolox.

The in vitro ABTS scavenging ability of Mn(II), Co(II), Ni(II) and Cu(II) complexes of naproxen was reported and the results are summarized in Table S5 and in Figure 26. Many of the complexes were significantly active towards ABTS radicals and were more potent than the reference compound trolox. Among the reported complexes, the best ABTS scavengers (Figure 26) were two nickel(II) complexes, i.e., [Ni(NAP)₂(CH₃OH)₄] (ABTS% = 96.03 ± 0.43%), [Ni(NAP)₂(Hpko)₂] (ABTS% = 97.73 ± 0.27%) and the manganese(II) complexes [Mn(NAP)₂(py)₂(H₂O)₂] (ABTS% = 94.78 ± 0.36%) and [Mn(NAP)₂(phen)(H₂O)] (ABTS% = 96.67 ± 0.68%) [42,43,61].

5.3.4. LOX Inhibitory Activity of the Complexes

LOX is the enzyme involved in a procedure occurring via carbon-centered radicals (lipoxygenation) [110]. The inhibition of LOX activity is often related with total antioxidant activity and free radical scavenging [111]. The ability of naproxen and its Ni(II) and Ag(I) complexes [50,61] to inhibit the activity of LOX was expressed as the concentration of the compound that inhibits the activity of the enzyme by 50% (IC₅₀) and was compared to the reference compounds caffeic acid and cisplatin (Table S6).

All of the Ni(II) and Ag(I) complexes tested were better LOX-inhibitors than free naproxen and especially than the reference compounds used in each case (Figure 27). Among the complexes tested, the silver(I) complexes were the most potent compounds with [Ag(NAP)(PPh₃)₃](H₂O) showing a very low IC₅₀ value (=5.1 µM).

5.3.5. SOD-like Activity of the Complexes

SOD is the enzyme that scavenges superoxide radicals and transforms them to oxygen and H₂O₂. Among the proposed mechanisms of anti-inflammatory activity of the NSAIDs, the inhibition of the generation of superoxide radicals [112] and the elimination of superoxide anions produced by nucleophiles [113] have also been considered. The SOD-like activity was reported for two Cu(II)–naproxen complexes (

Table 11. SOD-like activity (IC₅₀, in μM) of reported Cu(II)–naproxen complexes.

Compound	IC50 (μM)	Reference
[Cu2(NAP)4]n	0.3	[114]
[Cu(NAP)2(3pym)2]n	0.4	[114]
SOD enzyme	0.04–0.7	[114]

3pym = 3–pyridylmethanol; SOD = superoxide dismutase.

). The two reported complexes [Cu₂(NAP)₄]_n and [Cu(NAP)₂(3pym)₂]_n displayed significant SOD-like activity which was comparable to that of the enzyme [114].

5.4. Other Biological Activities

Other biological activities monitored for selected metal complexes include the catechol oxidase-like activity, the antimalarial activity and the reaction with linoleic acid.

In order to check the potential catalytic efficacy of two Cu(II)–naproxen complexes, i.e., the dinuclear [Cu₂(NAP)₄(3pic)₂] and the mononuclear complex [Cu(NAP)₂(4pic)₂(H₂O)], the catalytic two-electron oxidation of 3,5–di–tert–butylcatechol to the corresponding quinone 3,5–di–tert–butylquinone via the complexes was thoroughly studied [48]. The obtained results (kinetic parameters) revealed that the complexes possessed noteworthy catechol oxidase activity at room temperature. Especially, the catechol oxidase activity of the dinuclear complex [Cu₂(NAP)₄(3pic)₂] was significant when it was compared with the turnover number for the catechol oxidase enzyme [48].

A series of Zn(II)–naproxen complexes were checked for their in vitro antimalarial potency [63]. More specifically, six Zn(II)–naproxen complexes were monitored for the inhibition of the in vitro formation of β–hematin and the mononuclear complexes [Zn(NAP)₂(phen)] and [Zn(NAP)₂(neoc)], which both bear a phenanthroline-based co-ligand, and were the only active compounds. In particular, complex [Zn(NAP)₂(neoc)] was the most active among the tested complexes, showing an important inhibition of β–hematin formation in rather low concentrations (in the range 0.6–1 mg/mL) with efficacy > 75% which is comparable with the reference compounds Chloroquine and Amodiaquine [63].

The influence of complex [(n–Bu)₂Sn(NAP)₂] upon the peroxidation of linoleic acid was also monitored. The interaction of the complex with linoleic acid (an essential component of the cell membrane) resulted in increased amounts of hydroperoxylinoleic acid. Such a reaction could either decrease the quantity of linoleic acid in the cell membrane or even totally remove it from the membrane leading to serious damage and dysfunction of the membrane, which is important in the case of cytotoxicity studies [60].

5.5. Interaction of the Compounds with Biomacromolecules

Complimentary with biological activity studies, the interaction of bioactive compounds with biomacromolecules is often studied in order to evaluate the biological potency of the compounds and to check possible mechanistic pathways or biological targets. Overall, the most commonly studied biomacromolecules are DNA and albumins.

5.5.1. Interaction of the Reported Complexes with DNA

DNA is among the biomolecular targets for a series of drugs including antibacterial, antiviral and anticancer agents [115], because it can regulate genetic information and may affect the replication of the cell and the protein expression. DNA is involved in diverse mechanisms of action for such drugs, e.g., drugs such as methotrexate inhibit the nucleotide synthesis, others such as doxorubicin inhibit the activity of the topoisomerase enzyme and Pt-based drugs may intervene in double-strand DNA, further blocking its replication [116]. Metal-based drugs with labile ligands (e.g., cisplatin) may bind covalently to DNA bases via vacant coordination sites [117], while those containing non-labile ligands remain stable and may interact noncovalently with DNA by intercalation, groove-binding and/or electrostatic interaction [117,118]. In addition, the cleavage of DNA may also be a result of its interaction with metal complexes being able to act as chemical nucleases [118] and may occur simultaneously with tight DNA binding [119,120]. With DNA being a possible target of photodynamic therapy, the changes in the DNA helix induced by irradiation in the presence of metal complexes are also interesting to study [121,122,123].

Considering the reported metal complexes with the considered ligands, many metal–naproxen complexes have been studied for their interaction with calf thymus (CT) DNA, which is the most common form of linear DNA studied. The interaction of the complexes with CT DNA was studied using diverse techniques (UV–vis spectroscopy, cyclic voltammetry, viscosity measurements and fluorescence emission spectroscopy) aiming to determine the mode of this interaction and to calculate the DNA-binding constants (K_b). Most of the reported metal–naproxen complexes were proposed to interact with CT DNA by intercalation [42,43,49,50,56,60,61,90], i.e., via insertion of the aromatic ligands in between the DNA nucleobases which are further stabilized by the development of π–π stacking interactions.

The DNA-binding constants of the reported complexes were calculated using the Wolfe–Shimer equation [124] and their values are summarized in Table S7. The K_b values of the reported complexes were found in the range of 10⁴–10⁶ M⁻¹, revealing a tight interaction with CT DNA. Most of the complexes were found to be tighter DNA binders than the classic DNA intercalator ethidium bromide (EB) (K_b = 1.23 × 10⁵ M⁻¹) [125]. This fact was important for the employment of EB competitive displacement studies which were used to confirm the intercalative interaction with DNA. On the basis of K_b values (Table S7, Figure 28), the Ni(II) complexes were found to be the tightest DNA binders with all K_b values being higher than 10⁵ M¹ [61], while the highest K_b value was reported for complex [Mn(NAP)₂(phen)(H₂O)] (K_b = 6.40 × 10⁶ M⁻¹) [42].

In few cases, the supercoiled pBR322 plasmid DNA (pDNA) was used to study the interaction of circular DNA with complexes by gel electrophoretic experiments. More specifically, the interaction of [Cu(NAP)(L1)(Cl)], [Cu(NAP)(L2)(Cl)] and [Cu(NAP)(L3)(Cl)] with supercoiled pDNA revealed their high nuclease activity which resulted in the formation of nicked circular DNA or even linear DNA [49].

Furthermore, molecular docking calculations with DNA (PDB ID: 1BNA) were performed for a series of metal complexes in order to theoretically check the mode of DNA interaction and the DNA site where the interaction takes place. Molecular docking calculations with DNA were employed for complexes [Cu(NAP)(L1)(Cl)], [Cu(NAP)(L2)(Cl)] and [Cu(NAP)(L3)(Cl)] [49] and [(n–Bu)₂Sn(NAP)₂] [60], and the theoretical results were found to be in good agreement with the experimental findings regarding the mode of interaction and the relative affinity of the DNA interaction.

5.5.2. Interaction of the Reported Complexes with Albumins

Serum albumin (SA) is a multifunctional protein in blood serum. Its abundance is related with its important biological role, since it is responsible for the acid–base equilibrium in organisms, for the maintenance of osmotic pressure in blood and for the transportation of small molecules of hormones, fatty acids, ions and drugs through the bloodstream [126,127]. Additionally, albumins also have antioxidant and anticoagulant properties which are taken into consideration for potential clinical and pharmaceutical biochemical applications [128,129]. The most commonly studied albumins are human serum albumin (HSA) and its homolog—bovine serum albumin (BSA). The structures of both albumins have been characterized by crystallography. Their three domains (I, II and III) are divided in two subdomains (A and B) [130]. Sudlow’s site 1 (or drug site I) in subdomain IIA and Sudlow’s site 2 (or drug site II) in subdomain IIIA are the most important sites to host drugs and metal ions [130]. The intense fluorescence emission bands observed for both albumins, when their solutions are excited at 295 nm, are attributed to the presence of tryptophan residues; HSA has one tryptophan residue at position 214 and BSA has two tryptophans at positions 134 and 212 [130,131].

The interaction of the reported metal–naproxen complexes with both albumins was monitored by fluorescence emission quenching titrations [42,43,56,61,90]. The observed quenching was an indication of the noncovalent interaction of the compounds with the albumins [132]. The SA quenching constants (k_q) were calculated using the Stern–Volmer equation and plots [133]. The k_q values of the reported compounds for both albumins (Tables S8 and S9) are significantly higher than the value of 10¹⁰ M⁻¹ s⁻¹, suggesting the existence of a static quenching mechanism [134], which is confirmation of the noncovalent interaction of the compounds with the albumins. Among the reported complexes, the Ni(II)–naproxen complexes presented the highest k_q values for both albumins (Figure 29), i.e., [Ni(NAP)₂(phen)(H₂O)] and [Ni(NAP)₂(bipyam)] for BSA and [Ni(NAP)₂(bipyam)] and [Ni(NAP)₂(py)₂(H₂O)₂] for HSA [61].

The SA-binding constants (K) of the reported complexes were determined using the Scatchard equation and respective plots [133]. The K values of the reported compounds for both albumins (Tables S8 and S9) are higher than that of free naproxen and are of the 10⁴–10⁶ M⁻¹ magnitude [42,43,56,61,90]. These values are indicative of tight binding to both albumins which may be considered reversible, when compared with the highest noncovalent binding constant of value 10¹⁵ M⁻¹ [135]. This reversible binding may allow the release of the bioactive compounds when approaching their biological targets. Among the reported complexes, the manganese(II)–naproxen complexes presented the highest K values for both albumins (Figure 30), i.e., [Μn(NAP)₂(CH₃OH)]_n for BSA [90] and [Mn(NAP)₂(py)₂(H₂O)₂] for HSA [42].

6. Conclusions and Perspectives

As shown in the discussion, the presence of naproxen, 1–naphthylacetato, 2–naphthylacetato and 1–pyreneacetato ligands has generated a lot of interesting complexes concerning their structures and their photochemical and in vitro biological properties. The characterization of the complexes was achieved using X-ray crystallography and diverse physicochemical and spectroscopic techniques.

Among the metal ions participating in these complexes, most of them belong either to the first row transition metals (Ti(IV), Mn(II/III), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II)) or to lanthanides (Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III) and Yb(III)). Of course, there are some metal ions from second and third row transition metals (Y(III), Ru(II/III), Ag(I), Cd(II) and Au(I)) as well as from the s-block (Mg(II)) and p-block (Sn(IV)) of the periodic table. Indeed, the number of so-far-reported metal ions participating in such complexes is significant, leaving, however, opportunities and perspectives for the remaining transition metal ions that could also be taken into consideration for the formation of novel coordination compounds. The role and number of the co-ligands are important, since they contribute to the stabilization of the complexes and may offer, in most cases, synergism in the reported biological properties. Most of the co-ligands are oxygen–donors or heterocyclic nitrogen–donors.

Considering the nuclearity of the reported coordination compounds, most of them are mononuclear and dinuclear complexes. A few examples of trinuclear, tetranuclear and hexanuclear complexes have also been reported, where the ligands under study have mainly played an important bridging role. The reported polymeric complexes could be categorized to those owing their polymeric structure to bridges formed by the ligands under study and to compounds where naphthylacetato and naproxen ligands are terminal and do not contribute to the polymeric nature of the compounds.

The naproxen, 1–naphthylacetato, 2–naphthylacetato and 1–pyreneacetato ligands have been found in diverse coordination modes, either in one discrete mode or in a combination of two or even three different fashions. Monodentate and bidentate chelating modes and their combination were observed in the cases of mononuclear complexes. In the case of dinuclear, polynuclear and polymeric complexes, the concerned ligands were found in the bidentate (μ–O,O′) bridging mode either alone or in combination with the tridentate (μ–O,O,O′) bridging or bidentate chelating mode, in bidentate (μ–O,O) bridging fashion in combination with monodentate coordination or in the tridentate (μ–O,O,O′) bridging mode in combination with bidentate chelating binding. In the polynuclear complexes, the co-existence of other bridges such as µ–O or µ–shi–N,O contributed further to the formation of the polynuclear metallocyclic structures.

Among the physicochemical and spectroscopic techniques used, IR spectroscopy provided information regarding the coordination mode of the carboxylato ligands and the co-ligands. NMR, EPR and Mössbauer spectroscopies were also employed in cases where the nature of the metal ions allowed for their application. The photochemical properties of the complexes were focused on the study of the UV–vis spectra and the photoluminescence properties. The role and the choice of the naphthalene ring were crucial for these properties since the fluorescence properties of the transition metal complexes were assigned to intraligand π–π* transitions, while, for the lanthanide(III) complexes, they were attributed to f–f transitions. Thermogravimetric studies, magnetic measurements and cyclic voltammetry studies revealed their thermal, magnetic and electrochemical behavior, respectively.

The potential biological properties of selected reported complexes are significant. Selected complexes showed in vitro noteworthy cytotoxic potency towards diverse cancer cell lines which, in most cases, were even better than the reference compounds employed. The reported studies concerning the possible mechanism of cytotoxicity presented by selected complexes revealed their ability to induce apoptosis on studied cancer cell lines. The in vitro antibacterial activity of the selected complexes was evaluated against diverse microorganisms. The in vitro antioxidant activity of naproxen complexes was examined regarding free radical scavenging, the inhibition of the LOX enzyme and the SOD-like activity of selected compounds, and revealed their antioxidant potency. In addition, there are unique reports concerning the catalytic oxidation of 3,5–di–tert–butylcatechol to 3,5–di–tert–butylquinone, the in vitro antimalarial potency of a series of Zn(II)–naproxen complexes and the influence of a Sn(IV)–naproxen complex upon the peroxidation of linoleic acid. The interaction and affinity of selected naproxen complexes with CT DNA and serum albumins were studied in the context of their influence on biomacromolecules. All of these data have revealed the potential biological relevance of the so-far-reported coordination compounds of naproxen and 1– or 2–naphthylacetato ligands and may open novel pathways regarding biological activities and mechanisms.

In conclusion, naproxen, 1–naphthylacetic acid, 2–naphthylacetic and 1–pyreneacetic acid may serve as interesting ligands in their coordination compounds as their binding to metal ions has resulted in diverse interesting structures bearing noteworthy spectroscopic, magnetic and biological properties. The research concerning these ligands and possible derivatives may be focused on the use of unexplored metal ions for novel complexes, the formation of novel organic derivatives that may serve as ligands in future complexes by introducing modification in the naphthalene or pyrene rings and the in-depth investigation of the reported properties in order to explore potential mechanistic pathways and to reveal differentiated activities using more elaborate experimental and theoretical studies.