Synthesis of Peptides from Glycine on Anatases with Different Crystal Facets

Round 1

Reviewer 1 Report

 

The work of Chen et al., is an experimental investigation complemented by some thepretical calculations on the formation of glycine-based peptides on TiO2 anatase facets activated by heating and light.

The work is of interest in the community so my opinion that it deserves to be published in Crystals journal. However, I recommend the authors to follow my suggestions below with the good aim to improve the work.

Since the authors perform a short computational investigation on the adsorption of glycine on the anatase faces, it would be fair to cite some more extended Works dealing with the same topic, e.g., Pantaleone et al., J. Phys. Chem. C 2017, 121, 14156.

Ref. 7 does not refer to Goldschmidt work. Authors must correct this.

Title of subsection 2.6: H-NMR analysis

Some computational details in section 2.8 must be introduced: surface model, methodology for the calculations, software used, etc.    

Are the computational findings and the conclusions derived from the density differences consistent with the proposed mechanism in ref. 16?

Author Response

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Reviewer 2 Report

In this manuscript the authors present experimental measurements in order to probe the Gly polymerization process catalyzed by 2 different TiO2 anatase interfaces.

The results show that indeed TiO2 is able to facilitate the Gly condensation , being the facet 100 the one with higher activity.

The paper assesses the Gly condensation by using  different experimental methods such thermogravimetric analysis (TA), HPLC, NMR, IR and atomistic calculations.

My opinion is that the authors were able to demonstrate the catalytic action of TiO2 and its dependence on facet reactivity by TA and HPLC.

Nevertheless the rest of the measurements (NMR,IR and calculations) present either uncertainties or flaws, which do not support the main conclusion of the work.

The paper might be published after these parts are revised.

Specific criticisms:

NMR
The authors show the H chemical shift of Gly molecules after reaction with TiO2. They address the evidence of Gly condensation mainly to the amide peak at 8.5 ppm, citing reference 32. Anyway in the same reference it is shown that NHCO peaks can span different values. Moreover in the following reference it is debated that peaks around 8.5 might be the consequence of amide hydrogen bonding instead.

Int. J. Mol. Sci. 2002, 3(8), 907-913; https://doi.org/10.3390/i3080907

I suggest the authors revise this point.

Also it would help to measure and compare the reported spectra with the ones of pure  Gly or poly-Gly molecules.

IR
It is quite hard to discern any specific feature of the Gly condensation looking at the IR spectra. The authors discuss some very small blue-shift of some peaks upon temperature increase, but it seems to me that those peaks have a more oscillating trend. Temperature can modify the adsorption geometry of Glycine on the TiO2 surfaces, with consequent influence on the IR peaks. Moreover TiO2 might retain water molecules and hydroxyl groups, especially the 100 facet which is well known to undergo surface reconstruction involving water. All these species can contribute to changing the IR spectra with temperature.
Finally no spectra of the bare TiO2 surfaces and the Gly (single molecules or polymers)  are presented for comparison, thus it is impossible to determine how Gly interacts with TiO2.

DFT calculations.
The authors also report DFT calculation of Gly adsorbed on the TiO2 surfaces. Thise calculations are really not descriptive of the adoption process of Gly in real conditions. In general they do not provide any useful information about the Gly condensation. Water is not taken in consideration as well as the surface protonation state (and reconstruction for the 100 facet). These effects and the complexity of the adsorption and polymerization process of Gly on TiO2 surface were reported in several papers, I cite here the most recent I am aware of : Barcaro et al. "Experimental and theoretical elucidation of catalytic pathways in TiO2-initiated prebiotic polymerization Phys. Chem. Chem. Phys., 2019,21, 5435-5447" (see also references in the very same paper)

This and related references should be added to the manuscript.

It seems to me that these calculations are a mere decoration  rather than representing any scientific relevant point in the context of the manuscript.

 

 

Please, double check and revise the sentences along the text. There are cases where it is difficult to understand which is the subject of a sentence or what it is referring to.

Author Response

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Reviewer 3 Report

Minerals as substrates and catalysts of organic molecular reactions play and important role in the origin of early life. These minerals are exposed to temperature variations and light irradiation that further facilitate reactions on their surface. One or another reaction mechanism and pathway are key points determining specific reactions. Despite of a vast amount of works in this field, the issue relating to the effect of atomic structure of the mineral on the reaction on its surface remains largely unresolved. In relation to this, the present work, addressing the issue how the crystal structure of anatase catalyzes the condensation of glycine to form corresponding oligopeptides, fills this gap.

 

Using a complimentary set of sample preparation and characterization tools in combination with calculation modeling, it is demonstrated that anatase (001) crystal surface, compared to ordinary anatase, shows better catalytic effect, which can notably reduce the condensation temperature of glycine. Relation between the Gly2, Gly3 condensation efficiency, the anatase crystal structure and the temperature is obtained and analyzed. These findings are scientifically sound and make notable contribution to the field of study.

 

The strength of the work: Detail molecular-level insight into the catalytic efficiency of glycine in terms of dependence upon the anatase surface structure, on the basis of wide set of appropriate experimental techniques and modeling.

 

The weakness: Anatase, as one of the structural modification of titanium dioxide, is known as a substrate which is easily hydroxylated. Hydroxylation may dramatically change the catalytic performance. So the work would gain, if this issue was more detail  addressed, because exposure to atmospheric moisture, as well as to the ground water, may change the performance of anatase towards Gly condensation and reaction.

 

In general, the manuscript is scientifically sound with the appropriate experimental and model design to address the issues under consideration. It is clear, relevant for the field and presented in a well-structured manner. The manuscript provides sufficient details to reproduce results. Referencing is quite comprehensive and up-to-dated. The work is suitable for publications in its present form, with account of the following minor points:

 

 

 

11)    Although the acronyms HPLC, TA/DTA, NMR, DKP are of common use, they should be decoded in the abstract.

 

22)    What does mean “The ordinary anatase”? What is the difference with anatase (001)? It needs clarification.

 

 

33)    The authors stress the “semiconducting” nature of the substrate throughout the text. However, it is not clearly justified, what has the “semiconducting” nature to do with the reactions studied?

 

44)    Line 396: “… Figure 10… ” should probably be replaced by “ … Figure … 11”.

Author Response

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Round 2

Reviewer 2 Report

The authors provided the requested answers and modifications about NMR and IR data.

Concerning the DFT simulations I am still not convinced about their significance. Electron density differences of single adsorbed Glycine molecules are very little informative in a scenario where the entropic effects and the water surrounding play a determinant role in the Gly polymerization.

 The authors should remark this concept along the discussion of their atomistic calculation, pointing out the limits of these calculations in such a complex reactive scenario.

 

The quality of the language has been improved

Author Response

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