Towards a complete description of the reaction mechanisms between nitrenium ions and water.

Context: Nitrenium ions are intermediates in the metabolic routes producing the highly carcinogenic nitrosamines and binding to DNA molecules. The reaction mechanism of nitrenium molecules with explicit water molecules is sensibly dependent on the number of waters: when a second molecule is involved, it acts as a catalyst for the reaction, lowering intrinsic activation barriers regardless of the substituent. For all cases, the reaction force constants and reaction electron flux indicate highly synchronous reactions for .

Modeling UV/Vis Absorption Spectra of Food Colorants in Solution: Anthocyanins and Curcumin as Case Studies.

We present a comprehensive computational study of UV/Vis absorption spectra of significant food colorants, specifically anthocyanins and curcumin tautomers, dissolved in polar protic solvents, namely water and ethanol. The absorption spectra are simulated using two fully polarizable quantum mechanical (QM)/molecular mechanics (MM) models based on the fluctuating charge (FQ) and fluctuating charge and dipoles (FQFμ) force fields. To accurately capture the dynamical aspects of the solvation phenomenon, atomistic approaches are combined with configurational sampling obtained through classical molecular dynamics (MD) simulations.

Clinical Outcomes of Iris-Supported Phakic Toric Intraocular Lenses in Corneal Ectasia.

Introduction: Our aim was to evaluate the visual and refractive outcomes of iris-fixated phakic toric intraocular lenses (IOLs) for visual rehabilitation in eyes with stable corneal ectasia.

Methods: We conducted a study looking at the clinical outcomes of iris-fixated toric IOLs (Artisan) in 33 eyes of 27 patients diagnosed with mild-to-moderate corneal ectasia at a single center (Queen Victoria Hospital, East Grinstead, UK). The main outcome measures were functional improvement [accuracy of post-operative spherical equivalent (SE), astigmatic correction, topographic parameters, uncorrected and corrected distance visual acuity (UCVA, CDVA)] and safety of the procedure: endothelial cell count and intra- and post-operative complications.

Structural and Phylogenetic In Silico Characterization of PRR Protein as Potential Target for Infection.

Fungi infection, especially derived from , causes severe grapevine economic losses worldwide. Despite the availability of chemical treatments, looking for eco-friendly ways to control infection is gaining much more attention. When a plant is infected, multiple disease-control molecular mechanisms are activated.

The Role of Hydrogen Bonding in the Raman Spectral Signals of Caffeine in Aqueous Solution.

The identification and quantification of caffeine is a common need in the food and pharmaceutical industries and lately also in the field of environmental science. For that purpose, Raman spectroscopy has been used as an analytical technique, but the interpretation of the spectra requires reliable and accurate computational protocols, especially as regards the Resonance Raman (RR) variant. Herein, caffeine solutions are sampled using Molecular Dynamics simulations.

How to treat mixed behavior segments in supervised machine learning of behavioural modes from inertial measurement data.

The application of supervised machine learning methods to identify behavioural modes from inertial measurements of bio-loggers has become a standard tool in behavioural ecology. Several design choices can affect the accuracy of identifying the behavioural modes. One such choice is the inclusion or exclusion of segments consisting of more than a single behaviour (mixed segments) in the machine learning model training data.

When Tautomers Matter: UV-Vis Absorption Spectra of Hypoxanthine in Aqueous Solution from Fully Atomistic Simulations.

The UV-Vis spectrum of the solvated purine derivative Hypoxanthine (HYX) is investigated using the Quantum Mechanics/Fluctuating Charges (QM/FQ) multiscale approach combined with a sampling of configurations through atomistic Molecular Dynamics (MD) simulations. Keto 1H7H and 1H9H tautomeric forms of HYX are the most stable in aqueous solution and form different stable complexes with the surrounding water molecules, ultimately affecting the electronic absorption spectra. The final simulated spectrum resulting from the combination of the individual spectra of tautomers agrees very well with most of the characteristics in the measured spectrum.

Encapsulation of charged halogens by the 5 water cage.

This study focuses on the encapsulation of the entire series of halides by the 5 cage of twenty water molecules and on the characterization of water to water and water to anion interactions. State-of-the-art computations are used to determine equilibrium geometries, energy related quantities, and thermal stability towards dissociation and to dissect the nature and strength of intermolecular interactions holding the clusters as stable units. Two types of structures are revealed: heavily deformed cages for F indicating a preference for microsolvation, and slightly deformed cages for the remaining anions indicating a preference for encapsulation.

Computational Spectroscopy of Aqueous Solutions: The Underlying Role of Conformational Sampling.

Fully atomistic multiscale polarizable quantum mechanics (QM)/molecular mechanics (MM) approaches, combined with techniques to sample the solute-solvent phase space, constitute the most accurate method to compute spectral signals in aqueous solution. Conventional sampling strategies, such as classical molecular dynamics (MD), may encounter drawbacks when the conformational space is particularly complex, and transition barriers between conformers are high. This can lead to inaccurate sampling, which can potentially impact the accuracy of spectral calculations.

Protein-Protein Binding Kinetics by Biolayer Interferometry.

The specific kinetics and thermodynamics of protein-protein interactions underlie the molecular mechanisms of cellular functions; hence the characterization of these interaction parameters is central to the quantitative understanding of physiological and pathological processes. Many methods have been developed to study protein-protein interactions, which differ in various features including the interaction detection principle, the sensitivity, whether the method operates in vivo, in vitro, or in silico, the temperature control, the use of labels, immobilization, the amount of sample required, the number of measurements that can be accomplished simultaneously, or the cost. Bio-Layer Interferometry (BLI) is a label-free biophysical method to measure the kinetics of protein-protein interactions.

Close-Up Look at Electronic Spectroscopic Signatures of Common Pharmaceuticals in Solution.

Simulating electronic properties and spectral signals requires robust computational approaches that need tuning with the system's peculiarities. In this paper, we test implicit and fully atomistic solvation models for the calculation of UV-vis and electronic circular dichroism (ECD) spectra of two pharmaceutically relevant molecules, namely, (2)-captopril and ()-naproxen, dissolved in aqueous solution. Room temperature molecular dynamics simulations reveal that these two drugs establish strong contacts with the surrounding solvent molecules via hydrogen bonds.

Protein deuteration algal amino acids to circumvent proton back-exchange for H-detected solid-state NMR.

With perdeuteration, solid-state NMR spectroscopy of large proteins suffers from incomplete amide-proton back-exchange. Using a 72 kDa micro-crystalline protein, we show that deuteration exclusively deuterated amino acids, well-established in solution to suppress sidechain protonation without proton back-exchange obstacles, provides spectral resolution comparable to perdeuterated preparations at intermediate spinning frequencies.

Interactions and reactivity in crystalline intermediates of mechanochemical cyclorhodation reactions.

There is experimental evidence that solid mixtures of the rhodium dimer [Cp*RhCl] and benzo[] quinoline (BHQ) produce two different polymorphic molecular cocrystals called 4α and 4β under ball milling conditions. The addition of NaOAc to the mixture leads to the formation of the rhodacycle [Cp*Rh-(BHQ)Cl], where the central Rh atom retains its tetracoordinate character. Isolate 4β reacts with NaOAc leading to the same rhodacycle while isolate 4α does not under the same conditions.

Computational Insights into the Adsorption of Ligands on Gold Nanosurfaces.

We study the adsorption process of model peptides, nucleobases, and selected standard ligands on gold through the development of a computational protocol based on fully atomistic classical molecular dynamics (MD) simulations combined with umbrella sampling techniques. The specific features of the interface components, namely, the molecule, the metallic substrate, and the solvent, are taken into account through different combinations of force fields (FFs), which are found to strongly affect the results, especially changing absolute and relative adsorption free energies and trends. Overall, noncovalent interactions drive the process along the adsorption pathways.

Effective fully polarizable QM/MM approaches to compute Raman and Raman Optical Activity spectra in aqueous solution.

Raman and Raman Optical Activity (ROA) signals are amply affected by solvent effects, especially in the presence of strongly solute-solvent interactions such as Hydrogen Bonding (HB). In this work, we extend the fully atomistic polarizable Quantum Mechanics/Molecular Mechanics approach, based on the Fluctuating Charges and Fluctuating Dipoles force field to the calculation of Raman and ROA spectra. Such an approach is able to accurately describe specific HB interactions, by also accounting for anisotropic contributions due to the inclusion of fluctuating dipoles.

The Role of Crystalline Intermediates in Mechanochemical Cyclorhodation Reactions Elucidated by in-Situ X-ray Powder Diffraction and Computation.

The occurrence of crystalline intermediates in mechanochemical reactions might be more widespread than previously assumed. For example, a recent study involving the acetate-assisted C-H activation of N-Heterocycles with [Cp*RhCl ] by ball milling revealed the formation of transient cocrystals between the reagents prior to the C-H activation step. However, such crystalline intermediates were only observed through stepwise intervallic ex-situ analysis, and their exact role in the C-H activation process remained unclear.

Encapsulation of Astatide by a water cage.

A 5 cage of (HO) consisting of 30 hydrogen bonds encapsulates Astatide with little geometrical distortion. The cage is marginally destabilized but the non-covalent interactions are actually strengthened. Host⋯cage interactions in the [At@(HO)] cluster are anti-electrostatic, placing both negatively charged atoms in direct contact as in At⋯O-H.

Water Maintains the UV-Vis Spectral Features During the Insertion of Anionic Naproxen and Ibuprofen into Model Cell Membranes.

UV-vis spectra of anionic ibuprofen and naproxen in a model lipid bilayer of the cell membrane are investigated using computational techniques in combination with a comparative analysis of drug spectra in purely aqueous environments. The simulations aim at elucidating the intricacies behind the negligible changes in the maximum absorption wavelength in the experimental spectra. A set of configurations of the systems constituted by lipid, water, and drugs or just water and drugs are obtained from classical Molecular Dynamics simulations.

The transition state region in nonsynchronous concerted reactions.

The critical and vanishing points of the reaction force F(ξ) = -dV(ξ)/dξ yield five important coordinates (ξ, ξ , ξ, ξ , ξ) along the intrinsic reaction coordinate (IRC) for a given concerted reaction or reaction step. These points partition the IRC into three well-defined regions, reactants (ξ→ξ ), transition state (ξ →ξ ), and products (ξ →ξ), with traditional roles of mostly structural changes associated with the reactants and products regions and mostly electronic activity associated with the transition state (TS) region. Following the evolution of chemical bonding along the IRC using formal descriptors of synchronicity, reaction electron flux, Wiberg bond orders, and their derivatives (or, more precisely, the intensity of the electron activity) unambiguously indicates that for nonsynchronous reactions, electron activity transcends the TS region and takes place well into the reactants and products regions.

UV-Resonance Raman Spectra of Systems in Complex Environments: A Multiscale Modeling Applied to Doxorubicin Intercalated into DNA.

UV-Resonance Raman (RR) spectroscopy is a valuable tool to study the binding of drugs to biomolecular receptors. The extraction of information at the molecular level from experimental RR spectra is made much easier and more complete thanks to the use of computational approaches, specifically tuned to deal with the complexity of the supramolecular system. In this paper, we propose a protocol to simulate RR spectra of complex systems at different levels of sophistication, by exploiting a quantum mechanics/molecular mechanics (QM/MM) approach.

Multiple Facets of Modeling Electronic Absorption Spectra of Systems in Solution.

In this Perspective, we outline the essential physicochemical aspects that need to be considered when building a reliable approach to describe absorption properties of solvated systems. In particular, we focus on how to properly model the complexity of the solvation phenomenon, arising from dynamical aspects and specific, strong solute-solvent interactions. To this end, conformational and configurational sampling techniques, such as Molecular Dynamics, have to be coupled to accurate fully atomistic Quantum Mechanical/Molecular Mechanics (QM/MM) methodologies.

Dissecting Bonding Interactions in Cysteine Dimers.

Neutral () and zwitterionic () forms of cysteine monomers are combined in this work to extensively explore the potential energy surfaces for the formation of cysteine dimers in aqueous environments represented by a continuum. A simulated annealing search followed by optimization and characterization of the candidate structures afforded a total of 746 structurally different dimers held together via 80 different types of intermolecular contacts in 2894 individual non-covalent interactions as concluded from Natural Bond Orbitals (NBO), Quantum Theory of Atoms in Molecules (QTAIM) and Non-Covalent Interactions (NCI) analyses. This large pool of interaction possibilities includes the traditional primary hydrogen bonds and salt bridges which actually dictate the structures of the dimers, as well as the less common secondary hydrogen bonds, exotic X⋯Y (X = C, N, O, S) contacts, and H⋯H dihydrogen bonds.

Linear response properties of solvated systems: a computational study.

We present a computational study of static and dynamic linear polarizabilities in solution. We use different theoretical approaches to describe solvent effects, ranging from quantum mechanics/molecular mechanics (QM/MM) to quantum embedding approaches. In particular, we consider non-polarizable and polarizable QM/MM methods, the latter based on the fluctuating charge (FQ) force field.

Formation and evolution of C-C, C-O, C[double bond, length as m-dash]O and C-N bonds in chemical reactions of prebiotic interest.

A series of prebiotic chemical reactions yielding the precursor building blocks of amino acids, proteins and carbohydrates, starting solely from HCN and water is studied here. We closely follow the formation and evolution of the pivotal C-C, C-O, C[double bond, length as m-dash]O, and C-N bonds, which dictate the chemistry of the molecules of life. In many cases, formation of these bonds is set in motion by proton transfers in which individual water molecules act as catalysts so that water atoms end up in the products.

Microsolvation versus Encapsulation in Mono, Di, and Trivalent Cations.

The effects of the formal charge in the stability and bonding of water cavities when solvating a cation are studied here using [X(H O) ] clusters starting with the well known 5 isomer of (water) , placing a single mono, di, or trivalent X cation at the interior, and then optimizing and characterizing the resulting clusters. Highly correlated interaction and deformation energies are calculated using the CCSD(T)-DLPNO formalism. Bonding interactions are characterized using the tools provided by the quantum theory of atoms in molecules, natural bond orbitals, and non-covalent surfaces.