The influence of solvent representation on nuclear shielding calculations of protonation states of small biological molecules

In this study, we assess the influence of solvation on the accuracy and reliability of isotropic nuclear magnetic shielding calculations for amino acids in comparison to experimental data. We focus particularly on the performance of solvation methods for different protonation states, as biological molecules occur almost exclusively in aqueous solution and are subject to protonation with pH. We identify significant shortcomings of current implicit solvent models and present a hybrid solvation approach that improves agreement with experimental data by taking into account the presence of direct interactions between amino acid protonation state and water molecules

Quantum Chemistry Calculations for Metabolomics

A primary goal of metabolomics studies is to fully characterize the small-molecule composition of complex biological and environmental samples. However, despite advances in analytical technologies over the past two decades, the majority of small molecules in complex samples are not readily identifiable due to the immense structural and chemical diversity present within the metabolome. Current gold-standard identification methods rely on reference libraries built using authentic chemical materials (“standards”), which are not available for most molecules. Computational quantum chemistry methods, which can be used to calculate chemical properties that are then measured by analytical platforms, offer an alternative route for building reference libraries, i.e., in silico libraries for “standards-free” identification. In this review, we cover the major roadblocks currently facing metabolomics and discuss applications where quantum chemistry calculations offer a solution. Several successful examples for nuclear magnetic resonance spectroscopy, ion mobility spectrometry, infrared spectroscopy, and mass spectrometry methods are reviewed. Finally, we consider current best practices, sources of error, and provide an outlook for quantum chemistry calculations in metabolomics studies. We expect this review will inspire researchers in the field of small-molecule identification to accelerate adoption of in silico methods for generation of reference libraries and to add quantum chemistry calculations as another tool at their disposal to characterize complex samples.A primary goal of metabolomics studies is to fully characterize the small-molecule composition of complex biological and environmental samples. However, despite advances in analytical technologies over the past two decades, the majority of small molecules in complex samples are not readily identifiable due to the immense structural and chemical diversity present within the metabolome. Current gold-standard identification methods rely on reference libraries built using authentic chemical materials (“standards”), which are not available for most molecules. Computational quantum chemistry methods, which can be used to calculate chemical properties that are then measured by analytical platforms, offer an alternative route for building reference libraries, i.e., in silico libraries for “standards-free” identification. In this review, we cover the major roadblocks currently facing metabolomics and discuss applications where quantum chemistry calculations offer a solution. Several successful examples for nuclear magnetic resonance spectroscopy, ion mobility spectrometry, infrared spectroscopy, and mass spectrometry methods are reviewed. Finally, we consider current best practices, sources of error, and provide an outlook for quantum chemistry calculations in metabolomics studies. We expect this review will inspire researchers in the field of small-molecule identification to accelerate adoption of in silico methods for generation of reference libraries and to add quantum chemistry calculations as another tool at their disposal to characterize complex samples

Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata

A new flexible germacranolide (1, lobatolide H) was isolated from the aerial parts of Neurolaena lobata. The structure elucidation was performed by classical NMR experiments and DFT NMR calculations. Altogether, 80 theoretical level combinations with existing 13C NMR scaling factors were tested, and the best performing ones were applied on 1. 1H and 13C NMR scaling factors were also developed for two combinations utilizing known exomethylene containing derivatives, and the results were complemented by homonuclear coupling constant (JHH) and TDDFT-ECD calculations to elucidate the stereochemistry of 1. Lobatolide H possessed remarkable antiproliferative activity against human cervical tumor cell lines with different HPV status (SiHa and C33A), induced cell cycle disturbance and exhibited a substantial antimigratory effect in SiHa cells

Development and characterization of novel indigoid chromophores, photoswitches and molecular machinery

The photochemistry and photophysical properties of hemiindigo based photoswitches and indigo based molecular machines were examined. It could be shown that hemiindigos are a class of virtually unexplored, potent photoswitches supporting high photoisomerization ratios with blue over green to yellow and red light, high thermal bistabilities, good quantum yields and high tolerance of the photoreactions towards solvent polarity changes. The introduction of a chiral acyl or aryl axis on the hemiindigo chromophore at the indoxyl nitrogen was tested with various substitution patterns to explore the influence of electronics and sterics on the photophysical properties, electronic circular dichroism spectra and the motion of the passive chiral axes. Introduction of two chiral axes to the well-known indigo chromophore was carried out. The potential of these molecules as prospective molecular motors and -machines was demonstrated, giving insights into novel photoinduced- and thermal motions, which is crucial for the design of nanomachines and molecular robots. Also, addressability within the biooptical window was achieved, as all photosteps can be driven with low energy, 625 nm LED light, making the application of likewise systems available on biological tissues in vitro and in vivo. Three permanently charged, thermally bistable hemiindigos were synthesized and their photochemical properties in the gas phase and in solution were investigated. Several permanently charged hemiindigo photoswitches were tested in water and their photophysical properties as well as their ability to bind to DNA/RNA was scrutinized. Furthermore, the measurement procedures and automatization of photophysical measurements were improved

Synthesis, crystal structures and molecular modelling of rare earth complexes with bis(2-pyridylmethyl)amine: aim topological analysis and ligand conformation search

Eight rare earth complexes with bis(2-pyridylmethyl)amine (DPA) were synthesised and recrystallised, under air-sensitive or low moisture conditions. The crystal structures were successfully determined, via SC-XRD, and the asymmetric units of five complexes (1, 3, 5, 6 and 7) were submitted for DFT molecular modelling calculations, which involved geometry optimisation and frequency calculations. The neutral complexes obtained were bis(bis(2-pyridylmethyl)amine)-trichloro-lanthanum(III) [LaCl3(DPA)2] (1), bis(bis(2-pyridylmethyl)amine)-trichloro-cerium(III)) [CeCl3(DPA)2] (2), bis(μ2-chloro)-diaqua-tetrachloro-bis(bis(2-pyridylmethyl)amine)-di-praseodymium(III) [PrCl2(μ-Cl)(DPA)(OH2)]2 (3) and bis(μ2-methoxo)-bis(bis(2-pyridylmethyl)amine)- tetrachloro-di-dysprosium(III) [DyCl2(μ-OCH3)(DPA)]2 (4). The cationic complexes obtained in this study were dichloro-bis(bis(2-pyridylmethyl)amine)- neodymium(III) chloride methanol solvate [NdCl2(DPA)2]Cl·CH3OH (5), dichloro-bis(bis(2- pyridylmethyl)amine)-dysprosium(III) chloride methanol solvate [DyCl2(DPA)2]Cl·CH3OH (6), dichloro-bis(bis(2-pyridylmethyl)amine)-yttrium(III) chloride methanol solvate [YCl2(DPA)2]Cl·CH3OH (7) and dichloro-bis(bis(2-pyridylmethyl)amine)-lutetium(III) chloride methanol solvate [LuCl2(DPA)2]Cl·CH3OH (8). The ‘Quantum theory of atoms in molecules’ approach was used to investigate the electron density topology, primarily in order to investigate the hydrogen and coordination bonds for three of the eight complexes. Two of the neutral complexes contain the ‘early’ rare earth elements lanthanum and praseodymium and one cationic complex contains the ‘late’ lanthanide element dysprosium. Noncovalent interaction analysis was also performed on the aforementioned complexes in order to gain a deeper understanding of the intra-molecular stereo-electronic interactions. Spin density analysis was used to investigate the distribution of unpaired electron density at and around the metal centres of the aforementioned paramagnetic Pr- and Dy-complexes. A ligand conformation search for DPA was undertaken and 32 low energy conformers were identified and their relative energies were determined using two DFT functionals, namely M06 and M06-2X

Transition Metal Computational Catalysis: Mechanistic Approaches and Development of Novel Performance Metrics

Computational catalysis is an ever-growing field, thanks in part to the incredible progression of computational power and the efficiency offered by our current methodologies. Additionally, the accuracy of computation and the emergence of new methods that can decompose energetics and sterics into quantitative descriptors has allowed for researchers to begin to identify important structure-function relationships that predict the properties of unexplored subspaces within the overall chemical space. Catalytic descriptors have been used frequently in data driven high-throughput computational screenings. With the use of machine learning, a large portion of the chemical space an be predicted in matter of minutes or hours, instead of months and years. Herein, a full story of quantitative descriptors and computational catalysis is presented, where we have focused on developed metrics for understanding the underlying nature of dative bonding in main-group complexes and extended this into transition metal complexes. Additionally, the complexities of various catalytic reactions (hydrogen atom abstraction, aziridination, epoxidation and ring-opening metathesis polymerization) have been studied in depth to highlight the key features that lead to increased and decreased catalytic efficiency

Carbon Nanodots from an In Silico Perspective

Carbon nanodots (CNDs) are the latest and most shining rising stars among photoluminescent (PL) nanomaterials. These carbon-based surface-passivated nanostructures compete with other related PL materials, including traditional semiconductor quantum dots and organic dyes, with a long list of benefits and emerging applications. Advantages of CNDs include tunable inherent optical properties and high photostability, rich possibilities for surface functionalization and doping, dispersibility, low toxicity, and viable synthesis (top-down and bottom-up) from organic materials. CNDs can be applied to biomedicine including imaging and sensing, drug-delivery, photodynamic therapy, photocatalysis but also to energy harvesting in solar cells and as LEDs. More applications are reported continuously, making this already a research field of its own. Understanding of the properties of CNDs requires one to go to the levels of electrons, atoms, molecules, and nanostructures at different scales using modern molecular modeling and to correlate it tightly with experiments. This review highlights different in silico techniques and studies, from quantum chemistry to the mesoscale, with particular reference to carbon nanodots, carbonaceous nanoparticles whose structural and photophysical properties are not fully elucidated. The role of experimental investigation is also presented. Hereby, we hope to encourage the reader to investigate CNDs and to apply virtual chemistry to obtain further insights needed to customize these amazing systems for novel prospective applications

61st Annual Rocky Mountain Conference on Magnetic Resonance

Final program, abstracts, and information about the 61st annual meeting of the Rocky Mountain Conference on Magnetic Resonance, co-endorsed by the Colorado Section of the American Chemical Society and the Society for Applied Spectroscopy. Held in Copper Mountain, Colorado, July 25-29, 2022

Labelling of proteinaceous binders in art

Easel paintings are important Cultural Heritage assets with significant historic and cultural value. They usually possess a multi-tiered structure, composed of different layers, some of which may present protein binders. Proteins have been commonly used as paintings medium, adhesives and coating layers in easel paintings. Hence, their recognition is a crucial step for easel painting’s conservation and restoration processes. The present work presents a novel fluorescent labelling methodology, using a coumarin derivative chromophore, C392STP (sodium (E/Z)-4-(4-(2-(6,7- dimethoxycoumarin-3-yl)vinyl)benzoyl)-2,3,5,6-tetrafluorobenzenesulfonate) as a fluorophore probe to bond proteinaceous binders used in paintings. The method was developed and optimized using commercial proteins and proteins extracted from hen’s egg yolk and white, bovine milk, and rabbit skin. In order to mimic the real conditions, paint models of easel paintings have been prepared by mixing proteins such as ovalbumin, casein and rabbit glue with different pigments (lead white, chrome yellow and black bone) and the fluorescent labelling method was miniaturized and tested. The results revealed that proteins in concentration as low as 6.0 μg/ml could be detected. Finally, for validation methodology, real micro samples of easel paintings were analyzed. The extracted proteins were submitted to the fluorescent labelling method developed and clearly identified in electrophoretic profiles. The results evidence the applicability of this methodology as an effective and useful analytical tool for the identification of protein binders obtained from easel paintings and, possibly in other art work. Additionally, theoretical quantum chemical calculations based on the Density Functional Theory (DFT) and Time Dependent Density Functional Theory (TD-DFT) have been performed in the C392STP coumarin and in a related coumarin derivative ((E/Z)-4-(2-(6,7- dimethoxycoumarin-3- yl)vinyl)-N-propylbenzamide), that mimics the coumarin bonded to lysine. The calculations confirm the experimental trends in absorption wavelengths and are in good agreement with the experimental absorption spectra, providing a comprehensive characterization of the main spectral features of the studied compounds; RESUMO: Identificação de ligantes proteicos em arte As pinturas de cavalete são um componente importante do Património Cultural, com um significativo valor histórico e cultural. Geralmente possuem uma estrutura composta por diferentes camadas, algumas das quais podem apresentar ligantes proteicos. As proteínas surgem geralmente em pinturas de cavalete como meio de suporte da pintura, adesivos e camadas de revestimento. A sua identificação é, portanto, um passo crucial para os processos de conservação e restauração da pintura de cavalete. O presente trabalho apresenta uma nova metodologia de marcação fluorescente, utilizando um cromóforo derivado da cumarina, C392STP ((E/Z)-4-(2-(6,7- dimetoxicoumarin-3-yl)vinil)-N-propilbenzamida) como sonda fluorescente para marcar os ligantes proteicos usados em pinturas. O método foi desenvolvido e otimizado utilizando proteínas comerciais e proteínas extraídas da gema e clara de ovo de galinha, de leite de bovino e de pele de coelho. Para simular as condições reais, foram preparados modelos de pintura de pinturas de cavalete, misturando-se proteínas como ovalbumina, caseína e cola de coelho, com diferentes pigmentos (branco de chumbo, amarelo de crómio e negro de osso) e o método de marcação fluorescente foi miniaturizado e testado. Com base nos resultados obtidos, o método revelou-se capaz de detetar proteínas a concentração tão baixa quanto 6,0 μg / ml. Finalmente, para validação do método, foram analisadas micro amostras reais de pinturas de cavalete. As proteínas extraídas foram submetidas ao método de marcação fluorescente desenvolvido, tendo sido claramente identificadas em perfis eletroforéticos. Os resultados evidenciam a aplicabilidade desta metodologia como uma ferramenta analítica eficaz e útil para a identificação de ligantes proteicos extraídos de pinturas de cavalete e, possivelmente, de outras obras de arte. Adicionalmente, foram realizados cálculos quânticos baseados na Teoria Funcional da Densidade (DFT) e na Teoria do Funcional da Densidade Dependente do Tempo (TD-DFT) da cumarina C392STP de um derivado desta cumarina, ((E/Z)-N-propyl-4-(2-(6,7-dimethoxy-2-oxo-2H-chromen-3-yl)vinyl)benzamide)), que modela a cumarina ligada a lisina. Os cálculos confirmam as tendências experimentais observadas nos comprimentos de onda de absorção e estão de acordo com os espectros de absorção experimentais, fornecendo uma caracterização abrangente das principais características espectrais dos compostos estudados

58th Annual Rocky Mountain Conference on Magnetic Resonance

Final program, abstracts, and information about the 58th annual meeting of the Rocky Mountain Conference on Magnetic Resonance, co-endorsed by the Colorado Section of the American Chemical Society and the Society for Applied Spectroscopy. Held in Breckenridge, Colorado, July 17-21, 2016