Templated Crystallization of Glycine Homopeptides: Experimental and Computational Developments

Verma, Vivek; Mitchell, Hamish; Errington, Ethan; Guo, Mingxia; Heng, Jerry Y. Y.

doi:10.1002/ceat.202200575

Cited by 3 publications

(4 citation statements)

References 53 publications

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“…This was potentially due to the enhanced number of probable non-covalent interactions between the hydrogen bond donor of glycine and its homopeptides and the hydrogen bond acceptor of the glass beads. This was further corroborated with the molecular dynamics simulations, which confirmed the enhanced residence time of triglycine on the surface of the glass beads due to an increased number of hydrogen bond interactions [13,14].…”

Section: Introductionsupporting

confidence: 70%

“…Each experiment was carried out at least twice to ensure the reproducibility of the results. The induction time was accessed from the desupersaturation curves using the tangent method that was previously used by the authors [14].…”

Section: Isothermal Colling Crystallization Experimentsmentioning

confidence: 99%

“…This work focuses on improving the crystallization of peptides using the templated crystallization approach, already established by the authors [9,10,13,14]. The templates interact with the crystallising solute through functional group complementarity, allowing the sequestration of solute molecules on the surface of the templates with h-bond interactions for a long enough time to achieve a fully grown crystal.…”

Section: Introductionmentioning

confidence: 99%

“…The templates interact with the crystallising solute through functional group complementarity, allowing the sequestration of solute molecules on the surface of the templates with h-bond interactions for a long enough time to achieve a fully grown crystal. This was recently complemented with a molecular dynamics simulation, as mentioned earlier in the section [14]. In this work, diglycine was crystallised in the presence of different pore sizes of silica particles to examine the effect of template pore size on the crystallization time and rate.…”

Section: Introductionmentioning

confidence: 99%

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Experimental Elucidation of Templated Crystallization and Secondary Processing of Peptides

et al. 2023

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The crystallization of peptides offers a sustainable and inexpensive alternative to the purification process. In this study, diglycine was crystallised in porous silica, showing the porous templates’ positive yet discriminating effect. The diglycine induction time was reduced by five-fold and three-fold upon crystallising in the presence of silica with pore sizes of 6 nm and 10 nm, respectively. The diglycine induction time had a direct relationship with the silica pore size. The stable form (α-form) of diglycine was crystallised in the presence of porous silica, with the diglycine crystals obtained associated with the silica particles. Further, we studied the mechanical properties of diglycine tablets for their tabletability, compactability, and compressibility. The mechanical properties of the diglycine tablets were similar to those of pure MCC, even with the presence of diglycine crystals in the tablets. The diffusion studies of the tablets using the dialysis membrane presented an extended release of diglycine through the dialysis membrane, confirming that the peptide crystal can be used for oral formulation. Hence, the crystallization of peptides preserved their mechanical and pharmacological properties. More data on different peptides can help us produce oral formulation peptides faster than usual.

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Section: Introductionsupporting

confidence: 70%

Section: Isothermal Colling Crystallization Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Experimental Elucidation of Templated Crystallization and Secondary Processing of Peptides

et al. 2023

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Templated Nucleation of Clotrimazole and Ketoprofen on Polymer Substrates

Bellucci,

Yuan,

Woollam

et al. 2024

Mol. Pharmaceutics

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The use of different template surfaces in crystallization experiments can directly influence the nucleation kinetics, crystal growth, and morphology of active pharmaceutical ingredients (APIs). Consequently, templated nucleation is an attractive approach to enhance crystal nucleation kinetics and preferentially nucleate desired crystal polymorphs for solid-form drug molecules, particularly large and flexible molecules that are difficult to crystallize. Herein, we investigate the effect of polymer templates on the crystal nucleation of clotrimazole and ketoprofen with both experiments and computational methods. Crystallization was carried out in toluene solvent for both APIs with a template library consisting of 12 different polymers. In complement to the experimental studies, we developed a computational workflow based on molecular dynamics (MD) and derived descriptors from the simulations to score and rank API−polymer interactions. The descriptors were used to measure the energy of interaction (EOI), hydrogen bonding, and rugosity (surface roughness) similarity between the APIs and polymer templates. We used a variety of machine learning models (14 in total) along with these descriptors to predict the crystallization outcome of the polymer templates. We found that simply rank-ordering the polymers by their API− polymer interaction energy descriptors yielded 92% accuracy in predicting the experimental outcome for clotrimazole and ketoprofen. The most accurate machine learning model for both APIs was found to be a random forest model. Using these models, we were able to predict the crystallization outcomes for all polymers. Additionally, we have performed a feature importance analysis using the trained models and found that the most predictive features are the energy descriptors. These results demonstrate that API−polymer interaction energies are correlated with heterogeneous crystallization outcomes.

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The Effect of Template Reset Operation on the Number of Crystals Precipitated at the Air–Solution Template Interface

Tumurbaatar,

Amari,

Takiyama

2024

Crystals

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The application of template crystallization to developing novel crystalline materials has attracted attention. However, when the air–solution interface becomes the template interface and the target material crystallizes, new nucleation at the template interface is prevented, which is predicted to prevent the increase in the total number of crystals. In this study, we investigated the effect of operations that change the driving force at the air–solution template interface on the number of crystals at the interface. The number of crystals precipitated by changing the local supersaturation was investigated by a novel “template reset” operation, in which the concentration driving force near the template interface is changed by dissolving the crystals at the interface, once precipitated. The results showed that the number of crystals increased significantly after the template reset operation, and the particle size distribution was also improved. The temperature of the solution near the interface after the template reset operation was higher than that of the solution at the bottom of the petri dish and the prepared saturated solution, suggesting that the driving force of crystallization was higher.

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Templated Crystallization of Glycine Homopeptides: Experimental and Computational Developments

Cited by 3 publications

References 53 publications

Experimental Elucidation of Templated Crystallization and Secondary Processing of Peptides

Experimental Elucidation of Templated Crystallization and Secondary Processing of Peptides

Templated Nucleation of Clotrimazole and Ketoprofen on Polymer Substrates

The Effect of Template Reset Operation on the Number of Crystals Precipitated at the Air–Solution Template Interface

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