Hybrid or Component?—Schiff Base Complexes and Laccase

To date, only a few articles related to the hybrid materials of Schiff base metal complexes and laccase, an oxygen-reducing enzyme, have been published in Compounds since its inception in 2021. For example, Katsuumi et al. conducted the following work on hybrid materials [1]: As a mediator for electron transfer between the biofuel cell electrode and laccase, two oxovanadium complexes were used as promising redox active mediators. In addition to the literature preparation procedures of diamagnetic V(V) d⁰ and paramagnetic V(IV) d¹ complexes, respectively, their valences in solutions electrochemically characterized with CV were prepared by heating solutions to 363 K after isolating precipitates. However, the complexes exhibited ESR signals in the solid state at 300 K, and their effective magnetic moments at 300 K were 1.03 and 1.64 B.M., respectively, indicating somewhere between the S = 0 (V(IV) d⁰) and S = 1 (V(V) d¹) valence states. The results suggest that both oxovanadium complexes are easy to produce through redox reactions and the resulting precipitates are a mixture of V(V) and V(IV) complexes. Furthermore, the magnetic properites of laccase from Trametes versicolor have been reported, showing trinuclear active type 2 and type 3 copper sites and a type 1 copper site accepting electrons from a mediator. Details concerning the ESR, SQUID, CV data, DFT and docking to laccase of the complexes as PMMA cast films or solutions are also reported. Later, they developed such works to use Schiff base metal complexes as componets, too. Moreover, both chemical reports on Schiff base metal complexes and biophysical aspects of laccase studies have been reported in MDPI’s other journals. Herein, the author would like to introduce examples of such works.

In coordination chemistry, Schiff bases may be some of the most popular and useful organic ligands for the preparation of metal complexes. Here, the author discusses recent (2021 and 2022) papers published in the MDPI journal Inorganic in order to find the characteristics of pharmaceutical and biological Schiff base metal complexes by comparing them with other functional ones. In general, azomethine nitrogen atoms provide binding sites for metal ions to bind to various biomolecules such as proteins and amino acids. This interferes with normal cellular processes through hydrogen bonding with the active centers of cellular constituents. Aragón-Muriel et al. [1] summarized many research papers concerning Schiff base metal complexes incorporating tridentate “pincer” ligands for their use in antimicrobial or pharmaceutical applications. As a result of the chelating effect, pincer ligands form highly stable complexes with transition metals, preventing their degradation in physiological environments. Stability is a useful property during drug release at a specific pH. Arhouma et al. [2] reported the anticarcinogenic function of Mycobacterium smegmatis growth inhibition by vanadium complexes of Schiff base catecholates. They concluded that catecholate Schiff base vanadium complexes are more effective than free catecholates as a result of the combination of catechol properties, including toxicity, hydrophobicity, and steric factors. Northcote-Smith et al. [3] reported polypyridyl and naphthol Schiff base copper complexes that are active against breast cancer stem cells by elevating the level of intracellular reactive oxygen species. The mixed ligands are 1,10-phenanthoroline and a tridentate (O, N, S) coordinated naphthol Schiff base ligand. Sahu et al. [4] prepared distorted square-pyramidal vanadium complexes possessing tridentate ligands with imine-N, two phenoxide-O, and two oxido-O atoms in their center. The cytotoxicity of the complexes was measured against both cancer and normal cells, and the interactions with DNA were investigated to provide the binding information of the complexes (whose three-dimensional fitting may be important) with the DNA helix. Al-Shbou et al. [5] demonstrated the antimicrobial and anticancer activity of some Schiff base complexes of tetradentate, binding via the ONNO motif of the two phenolic oxygen atoms and two azomethine nitrogen atoms.

Besides typical salen-type [6] or N,O-bidendate [7] Schiff base ligands, recent synthetic works on Schiff base complexes have focused on wider scopes, such as coordination bond characteristics (π-backdonation from these metals to the azomethine of Schiff bases) [8] and the Lewis base adduct formation of two salen moieties acting as a flexible “molecular tweezer” [9]. With the exception of fluorescence probing, such as the salen Zn in [9], the nature of coordination bonds may not be useful for the biological activity ascribed to the intermolecular interaction or reactivity of Schiff base metal complexes. In addition, several studies have been conducted on magnetism [10,11,12]. The spin state [10] may be controlled by the strength of the ligand field, which is mainly dependent on donor atoms forming a coordination environment, while single-molecule magnetic behavior [11,12] may be dependent on the symmetry of the coordination environment and the interaction of metal ions or their spins. The intramolecular situation of the metal ions in Schiff base ligands may be important for these functional metal complexes. In this way, strategies for the molecular design of Schiff base metal complexes considering their biological activity are considerably different from those for a certain kind of functional materials, according to their requirements [13].

On the other hand, laccase belongs to the family of multicopper oxidases (commonly containing a “blue-copper” type 1 copper site, a “normal” type 2 copper site, and a “dinuclear” type 3 copper site) which catalyze the one-electron oxidation of a substrate (including a wide range of compounds such as monophenols, polyphenols, aromatic amines, aromatic thiols, lignin, and mediators containing metal ions) outside of the type 1 site with the concomitant four-electron reduction of molecular dioxygen to water at trinuclear clusters of type 2 and type 3 sites (which can potentially be applied to the cathodes of biofuel cells) [14,15,16]. Besides its various catalytic organic or bioorganic reactions, laccase can also be used for industrial applications, for example, in textile and paper pulp, bio-bleaching (the degradation of synthetic dyes and inks) and waste water treatment [15]. Ironically, the bioreactor performances were tested only in the oxidation of the artificial chemical mediator ABTS (2,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), although it was not included in target reactions of synthetic interest or radical mechanism [16].

Among the fifty articles published in the last three years, approximately ten [17,18,19,20,21,22,23,24] review articles about laccase have been published in MDPI journals in 2022. The topics focused on by the latest reviews are as follows: lignin biodegradation [17]; antibiotics for use in waste treatment and enzymatic degradation [18]; plastics biodegradation [19]; the antimicrobial activity of polyphenols [20]; organic synthesis using laccase [21]; biotechnology for bio-fermentation [22]; reducing environmental pollution [23]; and laccase-based biosensors and immobilization [24]. Except for biosensors and some organic syntheses, oxidization reactions using the reduction of type 1 copper sites seem to be more important than the reduction of oxygen into water.

The author and his colleagues have investigated appropriate metal complexes as mediators for laccase in order to ensure smooth electron transfer from cathode to laccase (type 1 site) in biofuel cells [25,26,27,28]. Although the author is an inorganic chemist dealing with coordination chemistry or bioinorganic chemistry, physical aspects were also considered in these studies of physical and inorganic chemistry. The topics of interest and techniques used are as follows: electron transfer associated with chiral-induced spin selectivity (without magnetic field) [25]; the Weigert effect (selected photoisomerization due to electric dipole transition) of azobenzene and polarized electronic spectroscopy [26]; the chiral molecular recognition of ligand–protein docking and density functional theory (DFT) computations based on crystal structures [27]; and redox reactions of paramagnetic or diamagnetic metal spices [28] using electrochemistry as well as electron spin resonance and magnetic measurements [1]. Conventionally, physical chemistry and solid-state physics or biophysics cannot be clearly separated. For example, an article on laccase was published in Biophysica in 2021, which investigated the effects of ionic liquids in solutions of laccase using molecular dynamics computation and experiments [29].