Templated Nucleation of Clotrimazole and Ketoprofen on Polymer Substrates DOI
Michael A. Bellucci, Lina Yuan, Grahame R. Woollam

и другие.

Molecular Pharmaceutics, Год журнала: 2024, Номер 21(9), С. 4576 - 4588

Опубликована: Авг. 20, 2024

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

Язык: Английский

Predicting crystal form stability under real-world conditions DOI Creative Commons
Dzmitry S. Firaha, Yifei Michelle Liu, Jacco van de Streek

и другие.

Nature, Год журнала: 2023, Номер 623(7986), С. 324 - 328

Опубликована: Ноя. 8, 2023

The physicochemical properties of molecular crystals, such as solubility, stability, compactability, melting behaviour and bioavailability, depend on their crystal form1. In silico form selection has recently come much closer to realization because the development accurate affordable free-energy calculations2-4. Here we redefine state art, primarily by improving accuracy calculations, constructing a reliable experimental benchmark for solid-solid differences, quantifying statistical errors computed free energies placing both hydrate structures different stoichiometries anhydrate same energy landscape, with defined error bars, function temperature relative humidity. calculated have standard 1-2 kJ mol-1 industrially relevant compounds, method place landscape can be extended other multi-component systems, including solvates. These contributions reduce gap between needs experimentalist capabilities modern computational tools, transforming structure prediction into more actionable procedure that used in combination evidence direct establish control5.

Язык: Английский

Процитировано

51
Frontiers of molecular crystal structure prediction for pharmaceuticals and functional organic materials DOI Creative Commons
Gregory J. O. Beran

Chemical Science, Год журнала: 2023, Номер 14(46), С. 13290 - 13312

Опубликована: Янв. 1, 2023

Molecular crystal structure prediction has matured to the point where it can routinely facilitate discovery and design of new organic materials.

Язык: Английский

Процитировано

41
MDverse, shedding light on the dark matter of molecular dynamics simulations DOI Creative Commons
Johanna K. S. Tiemann, Magdalena Szczuka, Lisa Bouarroudj

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Сен. 20, 2023

The rise of open science and the absence a global dedicated data repository for molecular dynamics (MD) simulations has led to accumulation MD files in generalist repositories, constituting dark matter — that is technically accessible, but neither indexed, curated, or easily searchable. Leveraging an original search strategy, we found indexed about 250,000 2000 datasets from Zenodo, Figshare Open Science Framework. With focus on produced by Gromacs software, illustrate potential offered mining publicly available data. We identified systems with specific composition were able characterize essential parameters simulation such as temperature length, could identify model resolution, all-atom coarse-grain. Based this analysis, inferred metadata propose engine prototype explore To continue direction, call community pursue effort sharing data, report standardize reuse valuable matter.

Язык: Английский

Процитировано

15
A dual growth mode unique for organic crystals relies on mesoscopic liquid precursors DOI Creative Commons

Manasa Yerragunta,

Akash Tiwari,

Rajshree Chakrabarti

и другие.

Communications Chemistry, Год журнала: 2024, Номер 7(1)

Опубликована: Авг. 28, 2024

Organic solvents host the synthesis of high-value crystals used as pharmaceuticals and optical devices, among other applications. A knowledge gap persists on how replacing hydrogen bonds polar attraction that dominate aqueous environments with weaker van der Waals forces affects growth mechanism, including its defining feature, whether grow classically or nonclassically. Here we demonstrate a rare dual mode etioporphyrin I crystals, enabled by liquid precursors associate crystal surfaces to generate stacks layers, which then laterally incorporating solute molecules. Our findings reveal mesoscopic solute-rich clusters, unique phase favored weak such those between organic solutes. The lateral spreading precursor-initiated layers crucially relies abundant supply directly from solution, bypassing diffusion along surface; direct incorporation pathway may, again, be solvents. Clusters evolve amorphous particles do not seamlessly integrate into lattices. Crystals growing fast mostly nonclassically at high supersaturations are excessively strained. interactions typical systems promote nonclassical modes supporting enabling multilayer stacks.

Язык: Английский

Процитировано

5
Unravelling the effect of molecular interactions on macroscale properties in Sustainion anion exchange membrane (AEM) under hydrated conditions using MD simulations DOI

Tamaghna Chakraborti,

Riya Sharma, Anand Narayanan Krishnamoorthy

и другие.

Journal of Membrane Science, Год журнала: 2024, Номер 705, С. 122887 - 122887

Опубликована: Май 17, 2024

Язык: Английский

Процитировано

3
What Has Carbamazepine Taught Crystal Engineers? DOI Creative Commons
Amy V. Hall, Aurora J. Cruz‐Cabeza, Jonathan W. Steed

и другие.

Crystal Growth & Design, Год журнала: 2024, Номер 24(17), С. 7342 - 7360

Опубликована: Июнь 21, 2024

The antiepilepsy drug carbamazepine is one of the most studied pharmaceuticals in world. rich story its solid forms, cocrystals, and formulation a microcosm topical world pharmaceutical materials. Understanding has required time, money, dedication from numerous researchers companies worldwide. This wealth knowledge provides opportunity to reflect on progress within crystal engineering field general. Perspective covers extensive form landscape applies these examples discuss answer fundamental questions discipline. encompasses screening methods, computational discovery, power influence understanding controlling crystals amorphous state, environmental legacy modern pharmaceuticals. broad but in-depth analysis vehicle into engineering, not only own right across spectrum organic materials science formulation. Discoveries demonstrate potential richness chemistry every drug.

Язык: Английский

Процитировано

3
MDverse: Shedding Light on the Dark Matter of Molecular Dynamics Simulations DOI Creative Commons
Johanna K. S. Tiemann, Magdalena Szczuka, Lisa Bouarroudj

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 2, 2023

The rise of open science and the absence a global dedicated data repository for molecular dynamics (MD) simulations has led to accumulation MD files in generalist repositories, constituting

Язык: Английский

Процитировано

6
Crystal Polymorph Search in the NPT Ensemble via a Deposition/Sublimation Alchemical Path DOI Creative Commons
Aaron J. Nessler, Okimasa Okada,

Yuya Kinoshita

и другие.

Crystal Growth & Design, Год журнала: 2024, Номер 24(8), С. 3205 - 3217

Опубликована: Март 9, 2024

The formulation of active pharmaceutical ingredients involves discovering stable crystal packing arrangements or polymorphs, each which has distinct pharmaceutically relevant properties. Traditional experimental screening techniques utilizing various conditions are commonly supplemented with in silico structure prediction (CSP) to inform the crystallization process and mitigate risk. Predictions often based on advanced classical force fields quantum mechanical calculations that model potential energy landscape but do not fully incorporate temperature, pressure, solution during search procedure. This study proposes an innovative alchemical path utilizes polarizable atomic multipole field predict structures direct sampling NPT ensemble. use (i.e., nonphysical) intermediates, a novel Monte Carlo barostat, orthogonal space tempering bias combine enhance efficiency deposition/sublimation phase transition. proposed algorithm was applied 2-((4-(2-(3,4-dichlorophenyl)ethyl)phenyl)amino)benzoic acid (Cambridge Crystallography Database Centre ID: XAFPAY) as case showcase algorithm. Each experimentally determined polymorph one molecule asymmetric unit successfully reproduced via approximately 1000 short 1 ns simulations per group where simulation initiated from random rigid body coordinates cell parameters. Utilizing two threads recent Intel CPU (a Xeon Gold 6330 at 2.00 GHz), using AMOEBA can be acquired 4 h (equating more than 300 ns/day all 112 threads/56 cores dual node) within Force Field X software (https://ffx.biochem.uiowa.edu). These results demonstrate step forward rigorous ensemble CSP open door future algorithms continuum solvation methods.

Язык: Английский

Процитировано

2
MDverse, shedding light on the dark matter of molecular dynamics simulations DOI Creative Commons
Johanna K. S. Tiemann, Magdalena Szczuka, Lisa Bouarroudj

и другие.

eLife, Год журнала: 2024, Номер 12

Опубликована: Авг. 30, 2024

The rise of open science and the absence a global dedicated data repository for molecular dynamics (MD) simulations has led to accumulation MD files in generalist repositories, constituting dark matter — that is technically accessible, but neither indexed, curated, or easily searchable. Leveraging an original search strategy, we found indexed about 250,000 2000 datasets from Zenodo, Figshare Open Science Framework. With focus on produced by Gromacs software, illustrate potential offered mining publicly available data. We identified systems with specific composition were able characterize essential parameters simulation such as temperature length, could identify model resolution, all-atom coarse-grain. Based this analysis, inferred metadata propose engine prototype explore To continue direction, call community pursue effort sharing data, report standardize reuse valuable matter.

Язык: Английский

Процитировано

2
MDverse: Shedding Light on the Dark Matter of Molecular Dynamics Simulations DOI Open Access
Johanna K. S. Tiemann, Magdalena Szczuka, Lisa Bouarroudj

и другие.

Опубликована: Сен. 20, 2023

The rise of open science and the absence a global dedicated data repository for molecular dynamics (MD) simulations has led to accumulation MD files in generalist repositories, constituting dark matter - that is technically accessible, but neither indexed, curated, or easily searchable. Leveraging an original search strategy, we found indexed about 250,000 2,000 datasets from Zenodo, Figshare Open Science Framework. With focus on produced by Gromacs software, illustrate potential offered mining publicly available data. We identified systems with specific composition were able characterize essential parameters simulation, such as temperature simulation length, identify model resolution, all-atom coarse-grain. Based this analysis, inferred metadata propose engine prototype explore collected To continue direction, call community pursue effort sharing data, increase populating standardizing reuse valuable matter.

Язык: Английский

Процитировано

4