Morphology Modulation in Self-Assembly of Chiral 2-Hydroxy-2-Phenylacetic Acids in Polymeric Diluents

Round 1

Reviewer 1 Report

The authors observed symmetric morphologies for enantiomeric MA. The paper may deserve the publication but the following points should be revised.

 

1.     Rotation direction change on increasing crystallization temperature can be crystal modification change. To confirm this, the authors are advised to perform WAXD measurements after crystallization at different crystallization temperatures.

2.     Figures 10-13 for (S)-MA as well as related descriptions, which are complementary figures and descriptions of Figures 7-9 for (R)-MA, should be moved to SI. 

3.     2.1. Apparatus section: "the polymer spherulites" should be "the MA spherulites".

4.     The photos during crystallization (not after completion) would give important and precious information. The authors are advised to show them.  

5.     Figure 5, the rotation direction should be the growth direction as in Figure 7, that is, all the arrows should be reversed in this figure.

6.     In the Introduction section and Results and Discussion section, the literature should be concerned with low molecular weight compounds not with chiral polymers such as PDLA and PLLA.

7.     On page 7, Type 1, Type 2 and Type 3 should be explained with schemes or models.

8.     On page 8, flat-on can be used for polymer crystals not for low molecular weight MA. If the authors would like to use this terminology, show the flat-on model as a scheme. 

Author Response

Authors’ responses/revisions in response to referee’s comments:

 

Reviewer 1

The authors observed symmetric morphologies for enantiomeric MA. The paper may deserve the publication but the following points should be revised.

1. Rotation direction change on increasing crystallization temperature can be crystal modification change. To confirm this, the authors are advised to perform WAXD measurements after crystallization at different crystallization temperatures.

Author’s revision: For the referee’s “rotation direction”, we suppose referee meant the lamellar bending sense change with Tc.

We did have WAXD for R- and S-MA, attached here for perusal:

 

Figure: WAXD diffractions of R- and S-mandelic acids crystallized at 30 ^oC.

Apparently, both R- and S-MA have only one same crystal lattice (monoclinic), which does not change with temperature of crystallization or in blends.

2. Figures 10-13 for (S)-MA as well as related descriptions, which are complementary figures and descriptions of Figures 7-9 for (R)-MA, should be moved to SI. 

Author’s revision: First of all, there is no Figure 13 as referee commented. There are only Figs 10-12 for (S)-MA. Secondly, we think that the SEM/POM results in Figs. 10-12 for (S)-MA are critical evidence for showing the opposite bending sense in comparison to that of R-MA, and they deserve to be in the main texts, rather than in SI. A total of 12 figures in one full-paper manuscript are not too many. Altogether, the manuscript texts+figures in template is only moderate 11 pages. This journal does not demand on a page-limit. We think we authors have the discretion of what are critical to be in the main texts.

3. 1. Apparatus section: "the polymer spherulites" should be "the MA spherulites".

Author’s revision: Corrected. Thanks.

4. The photos during crystallization (not after completion) would give important and precious information. The authors are advised to show them.  

Author’s revision/replies: Thanks. We have added new Figure 4 – in-situ growth from nucleation to completion, where smaller spherulites can be visible. Figure 4. In–situ evolution of MA morphology [from R-MA/PVPh (50/50)] upon solvent-evaporation crystallization at 60°C, from t to t+4.5 min, where t= initiation of first trace of nuclei.

5. Figure 5, the rotation direction should be the growth direction as in Figure 7, that is, all the arrows should be reversed in this figure.

Author’s revision/replies: In Fig. 5, there are no “arrows” in the micrographs, as referee so commented. We wonder what referee is referring to here?  Perhaps, meant for referring to Fig, 6? As we could not comprehend the comments/questions here, we cannot take action.

Or perhaps, referee meant to say about Fig. 4 (where there are arrow marks on schemes)? But referee pls. understand the arrows in Fig. 4 mean differently; they mean the direction of rotation of the Maltese-cross, and not the growth direction at all. As we are not sure what referee really meant to comment, we nevertheless have revised by removing all arrow marks in Fig. 4 to avoid confusion. The figure is understandable without the arrows anyway.

6. In the Introduction section and Results and Discussion section, the literature should be concerned with low molecular weight compounds not with chiral polymers such as PDLA and PLLA.

Author’s replies/revision: We believe that widening the literature background does not harm anything by comparing MA to polymers. High-MW polymers crystallize in many ways similarly to low-MW organic compounds. Spherulites have many characteristics that are same or similar in long-chain polymers and small-molecule compounds. That was our purpose.

For studies on low molecular weight compounds with chirality, we already cited five papers as listed again here:

1. Kovács, T.; Szücs, R.; Holló, G.; Zuba, Z.; Molnár, J.; Christenson, H.K.; Lagzi, I. Self-Assembly of Chiral Menthol Molecules from a Liquid Film into Ring-Banded Spherulites. Cryst. Growth Des. 2019, 19, 4063–4069.
2. Imai, H.; Oaki, Y. Emergence of helical morphologies with crystals: twisted growth under diffusion-limited conditions and chirality control with molecular recognition. CrystEngComm 2010, 12, 1679–1687.
3. Wei, K.T.; Ward, D.L. α-Hydroxyphenylacetic Acid: A Redetermination. Acta Crystallogr 1977, 797–800.
4. Patil, A.O.; Pennington, W.T.; Paul, I.C.; Curtin, D.Y.; Dykstra, C.E. Reactions of Crystalline (R)-(-)- and (S)-(+)-Mandelic Acid with Amines. Crystal Structure and Dipole Moment of (S)-Mandelic Acid. A Method of Determining Absolute Configuration of Chiral Crystals. J. Am. Chem. Soc. 1987, 109, 1529–1535.
5. Zhang, Y.; Mao, S.; Ray, A.K.; Rohani, S. Nucleation and growth kinetics of (R)-mandelic acid from aqueous solution in the presence of the opposite enantiomer. Cryst. Growth Des. 2010, 10, 2879–2887.

We also stated in R&D (line 2790: “As previously reported by Oaki, et al.[16], chiral aspartic acid had the same structure but faced opposite directions: D-Asp was left-handed, while L-Asp was right-handed.”

7. On page 7, Type 1, Type 2 and Type 3 should be explained with schemes or models.

Author’s replies/revision: We did specify the three different patterns with word-phrases: (1) circularly ringed (Type 1), (2) hexagon-shaped (Type 2) and (3) circularly core-striped (Type 3). Types 1,2,3 are simply just codes for differentiation purposes.

We did cite refs. 30,31 in these descriptions, and readers can refer to original publications if they want more details. We are not too sure whether it is proper to spend too much space by re-producing on literature-reported results in original articles (certainly, unless they are very critical for R&D analyses).

8. On page 8, flat-on can be used for polymer crystals not for low molecular weight MA. If the authors would like to use this terminology, show the flat-on model as a scheme. 

Author’s replies/revision: We are not sure that sci. terminologies have to be differentiated between the small-molecule compounds from polymers. Many science disciplines for polymer fields actually evolved from demonstrated experiences in small-molecules classical chemistry that have much longer histories than polymers. But to satisfy the referee, we have added a scheme to the figure, with caption: [Inset on lower right: flat-on crystal stacks]

 

 

 

Author Response File: Author Response.pdf

Reviewer 2 Report

  The manuscript entitled “Morphology Modulation in Self-Assembly of Chiral 2-Hydroxy-2-Phenylacetic Acids in Polymeric Diluents” (Manuscript ID: crystals-1750854) describes an investigation on the effects of controlling the lamellar bending sense on self-assembled crystals of the chiral 2-hydroxy-2-phenylacetic acids. In their study 2-hydroxy-2-phenylacetic acids or mandelic acids (MAs) were crystallized with poly(4-vinyl phenol) (PVPh). Polarized optical microscopy (POM) and scanning electron microscopy (SEM) were then used to characterize the morphologies of the crystalline structures. When MAs with opposite chirality (S- and R-) were crystallized in the presence of PVPh, the morphologies of the resultant MA crystals could be changed from ring-banded spherulites to highly dendritic spherulites depending on the amount of PVPh that was present. It was also found that the bending sense of the lamellae of MA in the dendritic spherulites was not controlled by the chirality of MA alone, but also by the crystallization temperature. It was found that the bending direction was controlled by chirality only at higher crystallization temperatures of 65 °C or above, while the dendritic spheres were found to exhibit bending directions that were opposite from those anticipated based on the chirality at lower crystallization temperatures.

 

The research is fascinating and should be of interest to researchers in a variety of fields, such as polymer science, self-assembly, crystal engineering, chirality, and materials science. The research was generally well-executed and well-supported by a good range of characterization methods. For the most part, the manuscript is well-written and clear, but there seems to be an issue with the reference citation program, as there are a number of instances where the phrase “Error! Reference source not found” appears in the manuscript. Overall, I believe that the manuscript is suitable for publication pending minor revisions, which are outlined below.

 

Line 36: “form” can be changed to “formed”.

 

Lines 63-64: The phrase “reduces the tendency crystallization of PEO” seems to be unclear.

 

Line 68: “At medium” can be changed to “As the medium”.

 

Lines 97-98: The phrase “to prevent uneven cross-sections and affected subsequent observations” seems to be unclear.

 

Lines 106-107, 132, 133-134, 134-135, 159-160, 172-173, 191, 195, 222, 224, 227, 229, 230, 234, 241, 243, 256-257, 258-259, 290-291, 300, 308-309, 310, 312, 323, 325, 327, 330: There are a number of places in the manuscript where the phrase “Error! Reference source not found.” appears. This may be due to issues with a reference citation program.

 

Line 162: “With increase of” can be changed to “With an increase of”.

 

Lines 205-206: References may be needed for the statement that for polymers the initial geomentry of the nucleus sheaf crystals may strongly govern the patterns of subsequent crystal growth into the final aggregated spherulites.

 

Line 278: “Chirality effect on the” can possibly be changed to “The effect of chirality on the”.

 

Line 340: “and crystallization temperature” can possibly be changed to “and the crystallization temperature”.

 

Line 346: “The molecular chirality on the bending sense” can possibly be changed to “The effect of the molecular chirality on the bending sense”.

 

Line 351: “dendritic spherulite” can possibly be changed to “dendritic spherulites”.

 

Author Response

Reviewer 2 

  The manuscript entitled “Morphology Modulation in Self-Assembly of Chiral 2-Hydroxy-2-Phenylacetic Acids in Polymeric Diluents” (Manuscript ID: crystals-1750854) describes an investigation on the effects of controlling the lamellar bending sense on self-assembled crystals of the chiral 2-hydroxy-2-phenylacetic acids. In their study 2-hydroxy-2-phenylacetic acids or mandelic acids (MAs) were crystallized with poly(4-vinyl phenol) (PVPh). Polarized optical microscopy (POM) and scanning electron microscopy (SEM) were then used to characterize the morphologies of the crystalline structures. When MAs with opposite chirality (S- and R-) were crystallized in the presence of PVPh, the morphologies of the resultant MA crystals could be changed from ring-banded spherulites to highly dendritic spherulites depending on the amount of PVPh that was present. It was also found that the bending sense of the lamellae of MA in the dendritic spherulites was not controlled by the chirality of MA alone, but also by the crystallization temperature. It was found that the bending direction was controlled by chirality only at higher crystallization temperatures of 65 °C or above, while the dendritic spheres were found to exhibit bending directions that were opposite from those anticipated based on the chirality at lower crystallization temperatures.

The research is fascinating and should be of interest to researchers in a variety of fields, such as polymer science, self-assembly, crystal engineering, chirality, and materials science. The research was generally well-executed and well-supported by a good range of characterization methods. For the most part, the manuscript is well-written and clear, but there seems to be an issue with the reference citation program, as there are a number of instances where the phrase “Error! Reference source not found” appears in the manuscript. Overall, I believe that the manuscript is suitable for publication pending minor revisions, which are outlined below.

Author’s replies/revision: Thanks a lot for Referee #2’s favorable appraisals.

Line 36: “form” can be changed to “formed”.

Author’s revision: Corrected. Thanks.

Lines 63-64: The phrase “reduces the tendency crystallization of PEO” seems to be unclear. 

Author’s revision: It should have been: “reduces the tendency of crystallization of PEO” Corrected. Thanks.

Line 68: “At medium” can be changed to “As the medium”.

Lines 97-98: The phrase “to prevent uneven cross-sections and affected subsequent observations” seems to be unclear.

Author’s revision: Corrected. Thanks.

Lines 106-107, 132, 133-134, 134-135, 159-160, 172-173, 191, 195, 222, 224, 227, 229, 230, 234, 241, 243, 256-257, 258-259, 290-291, 300, 308-309, 310, 312, 323, 325, 327, 330: There are a number of places in the manuscript where the phrase “Error! Reference source not found.” appears. This may be due to issues with a reference citation program.

Author’s revision/replies: In our word texts, we did not see such “Error! Reference source not found.”  We are at a loss why it occurred? Perhaps, after conversion to PDF file, they came out? We will do a conversion and check prior to re-submission.

Line 162: “With increase of” can be changed to “With an increase of”. 

Author’s revision: Corrected. Thanks.

Lines 205-206: References may be needed for the statement that for polymers the initial geomentry of the nucleus sheaf crystals may strongly govern the patterns of subsequent crystal growth into the final aggregated spherulites.

Author’s replies/revision: Yes, we agree. But we actually cited [30,31] in the texts following that statement. We now have moved these two refs to end of that statement.

Line 278: “Chirality effect on the” can possibly be changed to “The effect of chirality on the”.

Line 340: “and crystallization temperature” can possibly be changed to “and the crystallization temperature”. 

Line 346: “The molecular chirality on the bending sense” can possibly be changed to “The effect of the molecular chirality on the bending sense”. 

Line 351: “dendritic spherulite” can possibly be changed to “dendritic spherulites”.

Author’s revision: All above mentioned have been corrected one by one in due care. Thanks for keen checking on contents and expert opinions.

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Author Response File: Author Response.pdf

Reviewer 3 Report

The manuscript entitled: “Morphology Modulation in Self-Assembly of Chiral 2-Hy-droxy-2-Phenylacetic Acids in Polymeric Diluents” submitted to Crystals as Article describes self-assembly process of 2-hydroxy-2-phenylacetic acids (MA) in pure racemic form together with poly(4-vinyl phenol) (PVPh). Authors study the crystallization influence of the mixture MA:PVPh in rations 90:10 to 50:50 in 4 wt.% p-dioxane affected also by the temperature of annealing. Obtained samples were studied using polarized optical microscope and SEM. Authors observed three traits where the self-assembly crystallization occurs as straight dendrimers or bended ones for 50:50 mixture. Only in higher temperatures the crystallization occurred for bended assembly in accordance to chiral form of used MA.

The topic regarding the controlled properties of materials is important due to the control over their properties. In my opinion controlled crystallization/assembly processes will be the key to future tailoring of new materials for different applications. I do recommend this article for after addressing some issues.

Here is the list of issues that requires authors attention: 

1.     General: please correct the automatic insertion of figures in the whole manuscript. When transferred to another system the automatic option to link images with their reference in the text failed.

2.     General: Why differential scanning calorimetry study was not used to establish the phase transition temperatures more exactly for pure materials and for blends? In my opinion those results could reveal some information regarding the enthalpies values for different crystallization conditions. These information would enrich the manuscript.

3.     Results and discussion: Authors mentioned the performance of thickness measurements however do not show the results. Please add a section regarding the analysis of SEM images concerning the cross-section measurements. Did authors observe any difference in thickness of samples before and after crystallization?

4.     Fig. 1: In my opinion it would be beneficial to show an image with smaller magnification for the reader to have a general overview of the structure of sample’s larger area.

Author Response

Referee #3:

Here is the list of issues that requires authors attention:

1. General: please correct the automatic insertion of figures in the whole manuscript. When transferred to another system the automatic option to link images with their reference in the text failed.

Author’s revision/replies: The other referee (#2) also noticed such discrepancy. We did not see such “Error! Reference source not found.”  We are at a loss why it occurred? Perhaps, after conversion to PDF file, they came out? We will do a conversion and check prior to re-submission.

2. General: Why differential scanning calorimetry study was not used to establish the phase transition temperatures more exactly for pure materials and for blends? In my opinion those results could reveal some information regarding the enthalpies values for different crystallization conditions. These information would enrich the manuscript.

Author’s revision/replies: We understand the suggestion. However, characterization of DSC and data interpretations might lead to extreme length that might not be proper for original articles focusing on single subject of effect of chirality and temperature on lamellar bending. Subjects might be diffused.  We think separate work focusing on phase transition can be done in future.

3. Results and discussion: Authors mentioned the performance of thickness measurements however do not show the results. Please add a section regarding the analysis of SEM images concerning the cross-section measurements. Did authors observe any difference in thickness of samples before and after crystallization?

Author’s revision/replies: Referee #3 asked an excellent question. We did do thru-thickness SEM analysis of the specimens. Work is still on-going, not yet completed, and we aim to pursue it further after the current top-surface work is completed and documented. The results of all SEM analysis on thru-thickness and interpretations might lead to extreme length that might not be proper. We think it is more proper to summarize all those issues and great volume of data in future work for more complete discussion. To respond, we have deleted referring to thickness analysis from the texts (Experimental section).  A preliminary scheme of thru-thickness result (yet to be refined, waiting for more final results) is attached and shown here for referee’s reference.

4. 1: In my opinion it would be beneficial to show an image with smaller magnification for the reader to have a general overview of the structure of sample’s larger area.

Author’s revision/replies: Thanks. We have added new Figure 4 – in-situ growth from nucleation to completion, where smaller spherulites can be visible. Figure 4. In–situ evolution of MA morphology [from R-MA/PVPh (50/50)] upon solvent-evaporation crystallization at 60°C, from t to t+4.5 min, where t= initiation of first trace of nuclei.

 

 

Author Response File: Author Response.pdf