Computational Chemistry is currently a synergistic assembly between
calculations, simulation, machine learning (ML) and optimization strategies for describing, solving and predicting chemical data ...and related phenomena. These include accelerated literature searches, analysis and prediction of physical and quantum chemical properties, transition states, chemical structures, chemical reactions, and also new catalysts and drug candidates. The generalization of scalability to larger chemical problems, rather than specialization, is now the main principle for transforming chemical tasks in multiple fronts, for which systematic and cost-effective solutions have benefited from ML approaches, including those based on deep learning (e.g. quantum chemistry, molecular screening, synthetic route design, catalysis, drug discovery). The latter class of ML algorithms is capable of combining raw input into layers of intermediate features, enabling bench-to-bytes designs with the potential to transform several chemical domains. In this review, the most exciting developments concerning the use of ML in a range of different chemical scenarios are described. A range of different chemical problems and respective rationalization, that have hitherto been inaccessible due to the lack of suitable analysis tools, is thus detailed, evidencing the breadth of potential applications of these emerging multidimensional approaches. Focus is given to the models, algorithms and methods proposed to facilitate research on compound design and synthesis, materials design, prediction of binding, molecular activity, and soft matter behavior. The information produced by pairing Chemistry and ML, through data-driven analyses, neural network predictions and monitoring of chemical systems, allows (i) prompting the ability to understand the complexity of chemical data, (ii) streamlining and designing experiments, (ii) discovering new molecular targets and materials, and also (iv) planning or rethinking forthcoming chemical challenges. In fact, optimization engulfs all these tasks directly.
Abstract
Large Stokes shift fast emitters show a negligible reabsorption of their luminescence, a feature highly desirable for several applications such as fluorescence imaging, solar-light managing, ...and fabricating sensitive scintillating detectors for medical imaging and high-rate high-energy physics experiments. Here we obtain high efficiency luminescence with significant Stokes shift by exploiting fluorescent conjugated acene building blocks arranged in nanocrystals. Two ligands of equal molecular length and connectivity, yet complementary electronic properties, are co-assembled by zirconium oxy-hydroxy clusters, generating crystalline hetero-ligand metal-organic framework (MOF) nanocrystals. The diffusion of singlet excitons within the MOF and the matching of ligands absorption and emission properties enables an ultrafast activation of the low energy emission in the 100 ps time scale. The hybrid nanocrystals show a fluorescence quantum efficiency of ~60% and a Stokes shift as large as 750 meV (~6000 cm
−1
), which suppresses the emission reabsorption also in bulk devices. The fabricated prototypal nanocomposite fast scintillator shows benchmark performances which compete with those of some inorganic and organic commercial systems.
Inclusion complexes play a definite role in a variety of applications, ranging from drug solubilization to smart materials. This work presents a series of studies based on molecular dynamics, ...including potential of mean force calculations, and aiming at understanding the factors that govern inclusion. Naphthalene and its derivatives are used as guests for a common host, β-cyclodextrin. It is observed that the substitution of naphthalene promotes an increase in the complexation constant (up to 100-fold), irrespective of the nature of the substituent, the latter comprising small hydrophobic and hydrophilic (including charged) groups. It is also seen that entropy does not favor inclusion, the order of magnitude of the binding free energy being given by the enthalpic component, with a dominating guest-host interaction contribution. Desolvation penalizes the inclusion process, and is not observed in the vicinity of the hydrophilic and charged groups, which remain exposed to the solvent. Results suggest that substantial modulation of the inclusion complexes can be achieved imposing different substituents, with direct transposition for the modulation of properties in supramolecular structures based on these complexes.
A MD/PMF-based procedure is designed for quantification of the interaction and respective components, guiding complex formation in water between β-CD and several naphthalene derivatives, highlighting the relevance of substituents.
The understanding of the dynamical and mechanistic aspects that lie behind siRNA-based gene regulation is a requisite to boost the performance of siRNA therapeutics. A systematic experimental and ...computational study on the 3'-overhang structural requirements for the design of more specific and potent siRNA molecules was carried out using nucleotide analogues differing in structural parameters, such as sugar constraint, lack of nucleobase, distance between the phosphodiester backbone and nucleobase, enantioselectivity, and steric hindrance. The results established a set of rules governing the siRNA-mediated silencing, indicating that the thermodynamic stability of the 5'-end is a crucial determinant for antisense-mediated silencing but is not sufficient to avoid sense-mediated silencing. Both theoretical and experimental approaches consistently evidence the existence of a direct connection between the PAZ/3'-overhang binding affinity and siRNA's potency and specificity. An overall description of the systems is thus achieved by atomistic simulations and free energy calculations that allow us to propose a robust and self-contained procedure for studying the factors implied in PAZ/3'-overhang siRNA interactions. A higher RNAi activity is associated with a moderate-to-strong PAZ/3'-overhang binding. Contrarily, lower binding energies compromise siRNA potency, increase specificity, and favor siRNA downregulation by Ago2-independent mechanisms. This work provides in-depth details for the design of powerful and safe synthetic nucleotide analogues for substitution at the 3'-overhang, enabling some of the intrinsic siRNA disadvantages to be overcome.
Introduction
Aging is a demographic global trend and a challenge for public mental health; however, gaps persist for a comprehensive definition of mental health, risk, protective factors, and ...processes involved, which represent a greater problem in middle-income countries, where evidence is scarce.
Objectives
To identify combined mental health profiles in older adults, based on self-report of anxiety symptoms, depressive symptoms, and perception of well-being, and to identify risk and protective variables for each of the groups, based on a sample of older adults attending primary health care (PHC) centers in the Province of Concepción, Chile.
Methods
A convenience sample of 573 adults of both sexes, over 65 years, autonomous, attending PHC centers in the Province of Concepción, Chile, answered a set of instruments assessing anxiety symptoms (SCL-90), depressive symptoms (PHQ-9) and perception of well-being (Pemberton Happiness Index) and eventually associated variables that included sociodemographic and living arrangements, social participation, threatening life events (LTE), loneliness (ULS-3), and social support (MSPSS). Latent profile mixture analysis was used to identify groups of adults with similar mental health, and pertinence in each group was explained using random forests. The relationship between predictors and latent profiles were analyzed with multinomial regression.
Results
A solution of 4 groups with distinctive mental health profiles was determined: Group 1 (28%) with high depressive symptoms, high anxiety, and low well-being; Group 2 (32%) with moderate depressive symptoms, high anxiety and moderate well-being; Group 3 (24%) with moderate depressive symptoms, low anxiety and moderate well-being and; Group 4 (15%) characterized by individuals with low anxious or depressive symptoms, high well-being, and absence of mental disorder.
Using random forests, this model predicts 63% variance between groups. A large number of variables were found to significantly predict membership in one of the 4 groups. Specifically: gender, satisfaction with living arrangement, economic crisis, own disease, and death or illness of friend, perception of general health, intimate, relational and collective loneliness, social support from family and significant others, and social support from friends.
Conclusions
The 4-group classification is a parsimonious solution where group 1 characterize people with poor mental health; groups 2 and 3 languishing with high and low anxiety respectively; and group 4 healthy and flourishing. Overall, these groups highlight the role of close interpersonal relationships or primary ties, both in terms of intimacy versus loneliness/isolation and in satisfaction with living arrangements for the elderly. The importance of these psychosocial predictors on combined mental health in the elderly further the need to understand their role and mechanisms to design promotion and prevention strategies.
Disclosure of Interest
None Declared
Low-temperature neutron diffraction experiments at Formula: see text GPa have been conducted to investigate the magnetic structures of metallic Holmium at high pressures by employing a long d-spacing ...high-flux diffractometer and a Paris-Edinburgh press cell inside a cryostat. We find that at Formula: see text GPa and Formula: see text K, no nuclear symmetry change is observed, keeping therefore the hexagonal closed packed (hcp) symmetry at high pressure. Our neutron diffraction data confirm that the ferromagnetic state does not exist. The magnetic structure corresponding to the helimagnetic order, which survives down to 5 K, is fully described by the magnetic superspace group formalism. These results are consistent with those previously published using magnetization experiments.
Cellulose and cyclodextrins possess unique properties that can be tailored, combined, and used in a considerable number of applications, including textiles, coatings, sensors, and drug delivery ...systems. Successfully structuring and applying cellulose and cyclodextrins conjugates requires a deep understanding of the relation between structural, and soft matter behavior, materials, energy, and function. This review focuses on the key advances in developing materials based on these conjugates. Relevant aspects regarding structural variations, methods of synthesis, processing and functionalization, and corresponding supramolecular properties are presented. The use of cellulose/cyclodextrin conjugates as intelligent platforms for applications in materials science and pharmaceutical technology is also outlined, focusing on drug delivery, textiles, and sensors.
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•Distortion in γ-Cd opposes inclusion and binding.•Distortion is not significant in β-Cd, and larger guests promote higher binding constants.•Desolvation of host cavity and guest ...affect complex stability.•Complexes with γ-Cd are generally less stable than those with β-Cd.
Cyclodextrins (Cds) are versatile carbohydrate hosts for developing multifunctional nanostructures of pharmaceutical interest. Factors affecting the thermodynamic signatures and stability of β- and γ-Cd complexes are detailed at the atomic level. The MD/PMF-based method is combined with the description of the nature and strength of the inter-partner affinity. Naphthalene, adamantane and lycorine derivatives are used as models of drug-leading structures. Guest size affects Cd-guest contact and the inclusion degree, inducing Cd deformation, which opposes inclusion. Complexation depends on the available Cd cavity volume, as guest fitting variations and the enthalpy penalty from Cd deformation impact on the binding constants (promoting a reduction of up to 104). The often neglected Cd deformation plays, thus, an important role in the interaction behavior of larger cavity Cd-based systems, being crucial in carbohydrate-mediated recognition phenomena. It corresponds to an increase in energy of ca. 90 kJ mol−1 in the simpler analyzed model system.
The critical roles of solvent, enthalpic, and entropic contributions in complexes between different hyaluronic acid derivatives bearing monomeric β-cyclodextrin and adamantene moieties are assessed ...combining our previously designed free energy oriented method and a recently proposed density-based noncovalent interaction analysis. This establishes the relevant thermodynamics signatures and identifies the stabilizing/destabilizing noncovalent interactions within the complexes used as models for the junction points. It is observed that structural variations promote major changes in the thermodynamic variables. The presence of the amphiphilic chains emphasizes inclusion and drastically increases the binding constant (to ca. 1028). A comprehensive thermodynamic scheme is thus provided, in which host–guest interactions, host conformation, and solvation play the leading roles. These results have direct implications for the rational design of supramolecular materials with specific properties based on these host–guest systems.
Charge trapping phenomena and recombination centers were studied in three Cs2HfCl6 single crystals of slightly different stoichiometry grown by the vertical Bridgeman method. Electron paramagnetic ...resonance (EPR) spectra measured both before and after X-ray irradiation show creation of two distinct V k centers. One of them was V k(a) already known from a recent work by “R. Král, V. Babin, E. Mihoková, M. Buryi, V. V. Laguta, K. Nitsch, and M. Nikl, Luminescence and Charge Trapping in Cs2HfCl6 Single Crystals: Optical and Magnetic Resonance Spectroscopy Study, J. Phys. Chem. C 121, 12375–12382 (2017)”. Its quantity was different in each of the samples studied; the smallest, however, was in the one with the best stoichiometry. The second V k center presently observed has never been described before. Its existence at an almost undetectable level was observed only in two of the three crystals. Thermally stimulated luminescence (TSL) spectra measured in the three samples were evidently composed of at least 2–3 strongly overlapped components within the 10–500 K temperature range. This suggested the existence of several recombination centers activated by the depletion of specific charge carrier traps. The corresponding TSL glow curves composed of seven complex peaks demonstrated significant decrease of the peaks amplitude in the sample with the best stoichiometry. Along with decreased radioluminescence amplitude, the combined EPR and TSL study allowed us to assume the reduction of both the recombination and trap center concentration with the increased crystal quality.
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