Calculation of absolute molecular entropies and heat capacities made simple

Chemical Science, Год журнала: 2021, Номер 12(19), С. 6551 - 6568

Опубликована: Янв. 1, 2021

We propose a fully-automated composite scheme for the accurate and numerically stable calculation of molecular entropies by efficiently combining density-functional theory (DFT), semi-empirical methods (SQM), force-field (FF) approximations. The is systematically expandable can be integrated seamlessly with continuum-solvation models. Anharmonic effects are included through modified rigid-rotor-harmonic-oscillator (msRRHO) approximation Gibbs-Shannon formula extensive conformer ensembles (CEs), which generated metadynamics search algorithm extrapolated to completeness. For first time, variations ro-vibrational entropy over CE consistently accounted-for Boltzmann-population average. Extensive tests protocol two standard DFT approaches B97-3c B3LYP-D3 reveal an unprecedented accuracy mean deviations <1 cal mol-1 K-1 (about <1-2%) total gas phase medium-sized molecules. Even hardship case extremely flexible linear alkanes (C14H30-C16H34), errors only about 3 K-1. Comprehensive indicate relatively strong variation conformational on underlying level typical drug molecules, inferring complex potential energy surfaces as main source error. Furthermore, we show some application examples free differences in chemical reactions.

Язык: Английский

---

Mass Spectrometry-Based Techniques to Elucidate the Sugar Code

Chemical Reviews, Год журнала: 2021, Номер 122(8), С. 7840 - 7908

Опубликована: Сен. 7, 2021

Cells encode information in the sequence of biopolymers, such as nucleic acids, proteins, and glycans. Although glycans are essential to all living organisms, surprisingly little is known about “sugar code” biological roles these molecules. The reason glycobiology lags behind its counterparts dealing with acids proteins lies complexity carbohydrate structures, which renders their analysis extremely challenging. Building blocks that may differ only configuration a single stereocenter, combined vast possibilities connect monosaccharide units, lead an immense variety isomers, poses formidable challenge conventional mass spectrometry. In recent years, however, combination innovative ion activation methods, commercialization mobility–mass spectrometry, progress gas-phase spectroscopy, advances computational chemistry have led revolution spectrometry-based glycan analysis. present review focuses on above techniques expanded traditional glycomics toolkit provided spectacular insight into structure fascinating biomolecules. To emphasize specific challenges associated them, major classes mammalian discussed separate sections. By doing so, we aim put spotlight most important element glycobiology: themselves.

Язык: Английский

---

Efficient ethylene purification by a robust ethane-trapping porous organic cage

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Июнь 17, 2021

Abstract The removal of ethane (C 2 H 6 ) from its analogous ethylene 4 is paramount importance in the petrochemical industry, but highly challenging due to their similar physicochemical properties. use emerging porous organic cage (POC) materials for C /C separation still infancy. Here, we report benchmark example a truncated octahedral calix[4]resorcinarene-based POC adsorbent (CPOC-301), preferring adsorb than , and thus can be used as robust absorbent directly separate high-purity mixture. Molecular modelling studies suggest exceptional selectivity suitable resorcin[4]arene cavities CPOC-301, which form more multiple C–H···π hydrogen bonds with guests. This work provides fresh avenue utilize selective industrially important hydrocarbons.

Язык: Английский

---

Organic molecules with inverted gaps between first excited singlet and triplet states and appreciable fluorescence rates

Matter, Год журнала: 2021, Номер 4(5), С. 1654 - 1682

Опубликована: Март 19, 2021

Язык: Английский

---

CREST—A program for the exploration of low-energy molecular chemical space

The Journal of Chemical Physics, Год журнала: 2024, Номер 160(11)

Опубликована: Март 21, 2024

Conformer–rotamer sampling tool (CREST) is an open-source program for the efficient and automated exploration of molecular chemical space. Originally developed in Pracht et al. [Phys. Chem. Phys. 22, 7169 (2020)] as driver calculations at extended tight-binding level (xTB), it offers a variety molecular- metadynamics simulations, geometry optimization, structure analysis capabilities. Implemented algorithms include procedures conformational sampling, explicit solvation studies, calculation absolute entropy, identification protonation deprotonation sites. Calculations are set up to run concurrently, providing single-node parallelization. CREST designed require minimal user input comes with implementation GFNn-xTB Hamiltonians GFN-FF force-field. Furthermore, interfaces any quantum chemistry force-field software can easily be created. In this article, we present recent developments code show selection applications most important features program. An novelty refactored backend, which provides significant speed-up small or medium-sized drug molecules allows more sophisticated setups, example, mechanics/molecular mechanics minimum energy crossing point calculations.

Язык: Английский

---

Design, Synthesis, Docking, DFT, MD Simulation Studies of a New Nicotinamide-Based Derivative: In Vitro Anticancer and VEGFR-2 Inhibitory Effects

Molecules, Год журнала: 2022, Номер 27(14), С. 4606 - 4606

Опубликована: Июль 19, 2022

A nicotinamide-based derivative was designed as an antiproliferative VEGFR-2 inhibitor with the key pharmacophoric features needed to interact catalytic pocket. The ability of congener ((E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazono)ethyl)phenyl)nicotinamide), compound 10, bind enzyme demonstrated by molecular docking studies. Furthermore, six various MD simulations studies established excellent binding 10 over 100 ns, exhibiting optimum dynamics. MM-GBSA confirmed proper a total exact energy -38.36 Kcal/Mol. also revealed crucial amino acids in through free decomposition and declared interactions variation inside via Protein-Ligand Interaction Profiler (PLIP). Being new, its structure optimized DFT. DFT mode VEGFR-2. ADMET (in silico) profiling indicated examined compound's acceptable range drug-likeness. synthesized condensation N-(4-(hydrazinecarbonyl)phenyl)benzamide N-(4-acetylphenyl)nicotinamide, where carbonyl group has been replaced imine group. in-vitro were consonant obtained silico results prohibited IC50 value 51 nM. Compound showed effects against MCF-7 HCT 116 cancer cell lines values 8.25 6.48 μM, revealing magnificent selectivity indexes 12.89 16.41, respectively.

Язык: Английский

---

Aromatic nitrogen scanning by ipso -selective nitrene internalization

Science, Год журнала: 2023, Номер 381(6665), С. 1474 - 1479

Опубликована: Сен. 28, 2023

Nitrogen scanning in aryl fragments is a valuable aspect of the drug discovery process, but current strategies require time-intensive, parallel, bottom-up synthesis each pyridyl isomer because lack direct carbon-to-nitrogen (C-to-N) replacement reactions. We report site-directable C-to-N reaction allowing unified access to various pyridine isomers through nitrene-internalization process. In two-step, one-pot procedure, azides are first photochemically converted 3

Язык: Английский

---

Automated Molecular Cluster Growing for Explicit Solvation by Efficient Force Field and Tight Binding Methods

Journal of Chemical Theory and Computation, Год журнала: 2022, Номер 18(5), С. 3174 - 3189

Опубликована: Апрель 28, 2022

An automated and broadly applicable workflow for the description of solvation effects in an explicit manner is introduced. This method, termed quantum cluster growth (QCG), based on semiempirical GFN2-xTB/GFN-FF methods, enabling efficient geometry optimizations MD simulations. Fast structure generation provided using intermolecular force field xTB-IFF. Additionally, approach uses implicit model electrostatic embedding growing clusters. The novel QCG procedure presents a robust tool subsequent application higher-level (e.g., DFT) methods to study molecular geometries explicitly or average spectroscopic properties over ensembles. Furthermore, computation free energy with supermolecular can be carried out QCG. underlying process physically motivated by computing leading-order solute-solvent interactions first account conformational chemical changes due low-energy barrier processes. space explored NCI-MTD algorithm as implemented CREST program, combination metadynamics GFN2-xTB yields realistic solution reasonable energies various systems without introducing many empirical parameters. Computed IR spectra some solutes show better match experimental data compared well-established models.

Язык: Английский

---

Halogenation of the 3-position of pyridines through Zincke imine intermediates

Science, Год журнала: 2022, Номер 378(6621), С. 773 - 779

Опубликована: Ноя. 17, 2022

Pyridine halogenation reactions are crucial for obtaining the vast array of derivatives required drug and agrochemical development. However, despite more than a century synthetic endeavors, processes that selectively functionalize carbon-hydrogen bond in 3-position broad range pyridine precursors remain largely elusive. We report reaction sequence pyridyl ring opening, halogenation, closing whereby acyclic Zincke imine intermediates undergo highly regioselective under mild conditions. Experimental computational mechanistic studies indicate nature halogen electrophile can modify selectivity-determining step. Using this method, we produced diverse set 3-halopyridines demonstrated late-stage complex pharmaceuticals agrochemicals.

Язык: Английский

---

Multilayer stacks of polycyclic aromatic hydrocarbons

Nature Chemistry, Год журнала: 2022, Номер 14(4), С. 457 - 462

Опубликована: Фев. 7, 2022

Язык: Английский

---