H-bond Distances Research Articles

Insights into heme degradation and hydrogen peroxide induced dimerization of human neuroglobin.

In this work, we investigated the H2O2-induced oligomerization of wild-type human neuroglobin (hNgb) and of some selected variants (C46AC55A, Y44A, Y44F, Y44AC46AC55A, Y44AC46AC55A) to clarify how the process is affected by the Cys46/Cys55 disulfide bond and the distal H-bonding network and to figure out the molecular determinants of the H2O2-induced formation of amyloid type structures and hNgb aggregates. It turns out that hydrogen peroxide exerts a twofold effect on hNgb, inducing both heme breakdown and protein dimerization/polymerization. The enhanced resistance to the oxidizing effect of H2O2 of the disulfide free variants indicates that both effects are strictly influenced by the heme accessibility for H2O2. Most importantly, the H2O2-induced neuroglobin dimerization/polymerization turns out to be triggered by tyrosyl radicals resulting from the oxidizing action of Compound I ([Por•Fe(IV)=O]+). Peptide mapping indicates that the H2O2-induced dimerization/polymerization of hNgb mainly involves Tyr44, which forms covalent bonds with all the other tyrosine residues, with a minor contribution from Tyr88. The presented findings contribute further important pieces of information in the quest of identifying all capabilities of human neuroglobin and ultimately its physiological task.

Solvent-Templated Methylammonium-Based Ruddlesden-Popper Perovskites with Short Interlayer Distances.

Two-dimensional (2D) halide perovskites are exquisite semiconductors with great structural tunability. They can incorporate a rich variety of organic species that not only template their layered structures but also add new functionalities to their optoelectronic characteristics. Here, we present a series of new methylammonium (CH3NH3+ or MA)-based 2D Ruddlesden-Popper perovskites templated by dimethyl carbonate (CH3OCOOCH3 or DMC) solvent molecules. We report the synthesis, detailed structural analysis, and characterization of four new compounds: MA2(DMC)PbI4 (n = 1), MA3(DMC)Pb2I7 (n = 2), MA4(DMC)Pb3I10 (n = 3), and MA3(DMC)Pb2Br7 (n = 2). Notably, these compounds represent unique structures with MA as the sole organic cation both within and between the perovskite sheets, while DMC molecules occupy a tight space between the MA cations in the interlayer. They form hydrogen-bonded [MA···DMC···MA]2+ complexes that act as spacers, preventing the perovskite sheets from condensing into each other. We report one of the shortest interlayer distances (∼5.7-5.9 Å) in solvent-incorporated 2D halide perovskites. Furthermore, the synthesized crystals exhibit similar optical characteristics to other 2D perovskite systems, including narrow photoluminescence (PL) signals. The density functional theory (DFT) calculations confirm their direct-band-gap nature. Meanwhile, the phase stability of these systems was found to correlate with the H-bond distances and their strengths, decreasing in the order MA3(DMC)Pb2I7 > MA4(DMC)Pb3I10 > MA2(DMC)PbI4 ∼ MA3(DMC)Pb2Br7. The relatively loosely bound nature of DMC molecules enables us to design a thermochromic cell that can withstand 25 cycles of switching between two colored states. This work exemplifies the unconventional role of the noncharged solvent molecule in templating the 2D perovskite structure.

1H and 13C chemical shift-structure effects in anhydrous β-caffeine and four caffeine-diacid cocrystals probed by solid-state NMR experiments and DFT calculations.

By using density functional theory (DFT) calculations, we refined the H atom positions in the structures of β-caffeine (C), α-oxalic acid (OA; (COOH)2), α-(COOH)2·2H2O, β-malonic acid (MA), β-glutaric acid (GA), and I-maleic acid (ME), along with their corresponding cocrystals of 2 : 1 (2C-OA, 2C-MA) or 1 : 1 (C-GA, C-ME) stoichiometry. The corresponding 13C/1H chemical shifts obtained by gauge including projector augmented wave (GIPAW) calculations agreed overall very well with results from magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy experiments. Chemical-shift/structure trends of the precursors and cocrystals were examined, where good linear correlations resulted for all COO1H sites against the H⋯O and/or H⋯N H-bond distance, whereas a general correlation was neither found for the aliphatic/caffeine-stemming 1H sites nor any 13C chemical shift against either the intermolecular hydrogen- or tetrel-bond distance, except for the 13COOH sites of the 2C-OA, 2C-MA, and C-GA cocrystals, which are involved in a strong COOH⋯N bond with caffeine that is responsible for the main supramolecular stabilization of the cocrystal. We provide the first complete 13C NMR spectral assignment of the structurally disordered anhydrous β-caffeine polymorph. The results are discussed in relation to previous literature on the disordered α-caffeine polymorph and the ordered hydrated counterpart, along with recommendations for NMR experimentation that will secure sufficient 13C signal-resolution for reliable resonance/site assignments.

Local hydrogen bonding environment induces the deprotonation of surface hydroxyl for continuing ammonia decomposition.

There is still a paucity of fundamental understanding about the reaction of ammonia decomposition over TiO2, especially the role of water. Herein, FPMD and DFT calculations were used to address this concern. The results reveal that ammonia decomposition in pure ammonia causes the hydroxylation of the surfaces and reduction of the proton acceptor sites, making proton transfer (PT) difficult, increasing the distances between the NH3 and Obr sites and changing the adsorption configurations of NH3, which are not favourable for accepting protons from NH3 dissociation. When water is introduced, the local hydrogen bonding environment, consisting of NH3 and H2O with the H2O dynamically close to the ObrH, promotes the increase of the positive charge of H atoms from 0.133 to 1.47 e, which increases the ObrH bond dipole moment from 1.136 to 1.400 Debye, resulting in the shortening of the H-bond distances between NH3 and ObrH (1.858 vs. 1.945 Å of only NH3) and enlarging the ObrH bonds (0.980 vs. 1.120 Å). This reduces the activation energy barriers of ObrH deprotonation and causes the surfaces to have low hydroxyl coverage from 0.425 to 0.382 eV. Our study reveals the role of water and provides new insights into ammonia decomposition on TiO2.

Investigating the intermolecular interactions in the explicitly solvated complexes of lomustine with water and ethanol

Lomustine is an alkylating chemotherapy drug that is used to treat diverse types of cancer, including brain tumors, Hodgkin's lymphoma, and non-Hodgkin's lymphoma, which works by interfering with the DNA in cancer cells, preventing them from dividing and growing. As such the lipid bilayer of the cell and body fluids provides the environments in which lomustine (lmt) performs its biological function. Chemical reactions involving biological systems occur in the liquid phase, where accurate modeling of the reaction pathways considers the influence of the solvent used. Implicit solvation adequately accounts for these effects but falls short when evaluating solvent-solute interactions. This study aims to explore the structures, thermodynamics, reactivity, UV–vis spectroscopy, energy decomposition analysis, and the interaction energies of lmt with molecules of water and ethanol (n = 1, 2, and 3), using density functional theory (DFT) at the ωB97XD/6–311++G (d, p) level of theory. The thermodynamics results reveal that the polarity of water molecules significantly influences the interaction strength of the studied systems as the interaction observed between lmt with W1, Et1, and Et2 is feasible and spontaneous, compared to others. The stability of the different clusters depends on the intermolecular hydrogen bonds formed between the drug and the polar solvent as explicated by the H-bond interaction distance. Also, the interaction of lmt with each of the solvents causes a slight deformation in the geometry of the lmt, moreover, the reactivity descriptors predicted the interaction of lmt to increase with a corresponding increase in the addition of water molecules.

Synthesis, characterization of 4,4′-((1E,1′E)-hydrazine-1,2-diylidenebis(methanylylidene)) diphenol and the inclusion complex with γ-cyclodextrin as a fluorescent probe for detection of Al3+

The 4, 4′- ((1E, 1′E)-hydrazine-1,2-diylidenebis(methanylylidene)) diphenol (4-HBA) is successfully synthesized utilizing 4-hydroxybenzaldehyde (4-HB) and hydrazine hydrate as the starting materials. The synthesized 4-HBA is confirmed by the spectral analysis of 1H NMR, FT-IR, UV–Visible, and HR-Mass spectroscopy. The inclusion complexes of 4-HBA with γ-cyclodextrin are therefore investigated using UV and fluorescence spectroscopy. When γ-CD combined with 4-HBA, a 1:1 inclusion complex (ICs) is created that causes absorption and fluorescence spectral changes. The molecular computational analysis is carried out utilizing PM3 Gaussian software revealing the orientation of the synthetic 4-HBA within the γ-CD cavity. The HOMO-LUMO band gap and the DFT analysis specifically support the ICs, with the help of energy values and the H-bond distance. The hydrophobic contact between the host and guest molecules is strongly supported by the 1H NMR and 2-D NMR data, with the matching Ar-H proton moving to higher chemical shift values and the strong cross-correlation spot validating the conclusion. Al3+ sensing activity is observed using fluorescent probes in conjunction with UV and FL spectral analysis. Other metal ions are present in the solutions even though they are not readily available, most notably the Al3+ that binds to the fluorescent probe. Here, the Al3+ selective responses, the colour changes at the wavelength regions, and a fluorescence microscopic image of the solution media are also shown. The selected metal ions recovery percentage is used to determine the concentrations in a variety of clean water samples, including tap water, pond water, and also sea water.

High-Order Quantum-Mechanical Analysis of Hydrogen Bonding in Hachimoji and Natural DNA Base Pairs.

High-order quantum chemistry is applied to hydrogen-bonded natural DNA nucleobase pairs [adenine:thymine (A:T) and guanine:cytosine (G:C)] and non-natural Hachimoji nucleobase pairs [isoguanine:1-methylcytosine (B:S) and 2-aminoimidazo[1,2a][1,3,5]triazin-4(1H)-one:6-amino-5-nitropyridin-2-one (P:Z)] to see how the intermolecular interaction energies and their energetic components (electrostatics, exchange-repulsion, induction/polarization, and London dispersion interactions) vary among the base pairs. We examined the Hoogsteen (HG) geometries in addition to the traditional Watson-Crick (WC) geometries. Coupled-cluster theory through perturbative triples [CCSD(T)] extrapolated to the complete basis set (CBS) limit and high-order symmetry-adapted perturbation theory (SAPT) at the SAPT2+(3)(CCD)δMP2/aug-cc-pVTZ level are used to estimate highly accurate noncovalent interaction energies. Electrostatic interactions are the most attractive component of the interaction energies, but the sum of induction/polarization and London dispersion is nearly as large, for all base pairs and geometries considered. Interestingly, the non-natural Hachimoji base pairs interact more strongly than the corresponding natural base pairs, by -21.8 (B:S) and -0.3 (P:Z) kcal mol-1 in the WC geometries, according to CCSD(T)/CBS. This is consistent with the H-bond distances being generally shorter in the non-natural base pairs. The natural base pairs are energetically more stabilized in their Hoogsteen geometries than in their WC geometries. The Hoogsteen geometry makes the A:T base pair slightly more stable, by -0.8 kcal mol-1, and it greatly stabilizes the G:C+ base pair, by -15.3 kcal mol-1. The G:C+ stabilization is mainly due to the fact that C has typically added a proton when found in Hoogsteen geometries. By contrast, Hoogsteen geometries are substantially less favorable than WC geometries for non-natural Hachimoji base pairs, by 17.3 (B:S) and 13.8 (P:Z) kcal mol-1.

Hydroxamic acid derivatives as selective HDAC3 inhibitors: computer-aided drug design strategies

Histone deacetylases (HDACs) are critical epigenetic drug targets that have gained significant attention in the scientific community for the treatment of cancer. The currently marketed HDAC inhibitors lack selectivity for the various HDAC isoenzymes. Here, we describe our protocol for the discovery of novel potential hydroxamic acid based HDAC3 inhibitors through pharmacophore modeling, virtual screening, docking, molecular dynamics (MD) simulation and toxicity studies. The ten pharmacophore hypotheses were established, and their reliability was validated by different ROC (receiving operator curve) analysis. Among them, the best model (Hypothesis 9 or RRRA) was employed for searching SCHEMBL, ZINC and MolPort database to screen out hit molecules as selective HDAC3 inhibitors, followed by different docking stages. MD simulation (50 ns) and MMGBSA study were performed to study the stability of ligand binding modes and with the help of trajectory analysis, to calculate the ligand-receptor complex RMSD (root-mean-square deviation), RMSF (root-mean-square fluctuation) and H-bond distance, etc. Finally, in-silico toxicity studies were performed on top screened molecules and compared with reference drug SAHA and established structure-activity relationship (SAR). The results indicated that compound 31, with high inhibitory potency and less toxicity (probability value 0.418), is suitable for further experimental analysis. Communicated by Ramaswamy H. Sarma

A Mechanistic Study of Asymmetric Transfer Hydrogenation of Imines on a Chiral Phosphoric Acid Derived Indium Metal-Organic Framework

A density functional theory (DFT) study is reported to examine the asymmetric transfer hydrogenation (ATH) of imines catalyzed by an indium metal-organic framework (In-MOF) derived from a chiral phosphoric acid (CPA). It is revealed that the imine and reducing agent (i.e., thiazoline) are simultaneously adsorbed on the CPA through H-bonding to form an intermediate, subsequently, a proton is transferred from thiazoline to imine. The transition state TS-R and TS-S are stabilized on the CPA via H-bonding. Compared to the TS-S, the TS-R has shorter H-bonding distances and longer C-H···π distances, it is more stable and experiences less steric hindrance. Consequently, the TS-R exhibits a lower activation barrier affording to the (R)-enantiomer within 68.1% ee in toluene. Imines with substituted groups such as -NO2, -F, and -OCH3 are used to investigate the substitution effects on the ATH. In the presence of an electron-withdrawing group like -NO2, the electrophilicity of imine is enhanced and the activation barrier is decreased. The non-covalent interactions and activation-strain model (ASM) analysis reveal that the structural distortions and the differential noncovalent interactions of TSs in a rigid In-MOF provide the inherent driving force for enantioselectivity. For -OCH3 substituted imine, the TS-S has the strongest steric hindrance, leading to the highest enantioselectivity. When the solvent is changed from toluene to dichloromethane, acetonitrile, and dimethylsulfoxide with increasing polarity, the activation energies of transition state increase whereas their difference decreases. This implies the reaction is slowed down and the enantioselectivity becomes lower in a solvent of smaller polarity. Among the four solvents, toluene turns out to be the best for the ATH. The calculated results in this study are in fairly good agreement with experimental observations. This study provides a mechanistic understanding of the reaction mechanism, as well as substitution and solvent effects on the activity and enantioselectivity of the ATH. The microscopic insights are useful for the development of new chiral MOFs toward important asymmetric reactions.

Origins of the diffuse shared proton vibrational signatures in proton-coupled electron transfer model dyad complexes.

Phenol-benzimidazole and phenol-pyridine dyad complexes have served as popular model systems for the study of proton-coupled electron transfer (PCET) kinetics in solution-phase experiments. Interpretation of measured PCET rates in terms of key structural parameters, such as the H-bond donor-acceptor distance, however, remains challenging. Herein, we report vibrational spectra in the electronic ground state for a series of phenol-benzimidazole and phenol-pyridine complexes isolated and cryogenically cooled in an ion trap. The four models studied each display highly red-shifted and broadened OH stretching transitions that arise from strong H-bonding interactions between the phenol OH group and the basic N site on benzimidazole/pyridine rings. The OH stretch transition in each model displays relatively strong absorption onsets near 2500cm-1 with broad shoulders that extend asymmetrically to higher frequencies over hundreds of wavenumbers. In contrast, the deuterated isotopologues yield much weaker OD stretch transitions that appear symmetrically broadened. The spectral breadth and shape of the OD stretch transitions are ascribed to variations in OD stretch frequencies that arise from zero-point distributions in the proton donor-acceptor low-frequency soft mode vibration. The asymmetric structure of the OH stretch transitions is attributed to a set of combination bands between the OH stretch and a series of low-frequency H-bond soft modes. The spectra and modeling highlight the importance of OH stretch-soft mode couplings, which are thought to play important roles in PCET and proton transfer dynamics.

Control of Tyrosyl Radical Stabilization by {SiO2@Oligopeptide} Hybrid Biomimetic Materials.

Tyrosine radicals are notoriously short-lived/unstable in solution, while they present an impressive degree of stability and versatility in bioenzymes. Herein, we have developed a library of hybrid biomimetic materials (HBMs), which consists of tyrosine-containing oligopeptides covalently grafted on SiO2 nanoparticles, and studied the formation, lifetime, and redox properties of tyrosyl radicals. Using electron paramagnetic resonance spectroscopy, we have studied the radical-spin distribution as a probe of the local microenvironment of the tyrosyl radicals in the HBMs. We find that the lifetime of the tyrosyl radical can be enhanced by up to 6 times, by adjusting three factors, namely, a proximal histidine, the length of the oligopeptide, and the interface with the SiO2 nanomatrix. This is shown to be correlated to a significant lowering of E1/2 from +736 mV, in free tyrosine, to +548 mV in the {12-peptide}@SiO2 material. Moreover, we show that grafting on SiO2 lowers the E1/2 of tyrosine radicals by ∼50 mV in all oligopeptides. Analysis of the spin-distribution by EPR reveals that the positioning of a histidine at a H-bonding distance from the tyrosine further favors tyrosine radical stabilization.

19F Electron-Nuclear Double Resonance Reveals Interaction between Redox-Active Tyrosines across the α/β Interface of E. coli Ribonucleotide Reductase.

Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to deoxyribonucleotides, thereby playing a key role in DNA replication and repair. Escherichia coli class Ia RNR is an α2β2 enzyme complex that uses a reversible multistep radical transfer (RT) over 32 Å across its two subunits, α and β, to initiate, using its metallo-cofactor in β2, nucleotide reduction in α2. Each step is proposed to involve a distinct proton-coupled electron-transfer (PCET) process. An unresolved step is the RT involving Y356(β) and Y731(α) across the α/β interface. Using 2,3,5-F3Y122-β2 with 3,5-F2Y731-α2, GDP (substrate) and TTP (allosteric effector), a Y356• intermediate was trapped and its identity was verified by 263 GHz electron paramagnetic resonance (EPR) and 34 GHz pulse electron–electron double resonance spectroscopies. 94 GHz 19F electron-nuclear double resonance spectroscopy allowed measuring the interspin distances between Y356• and the 19F nuclei of 3,5-F2Y731 in this RNR mutant. Similar experiments with the double mutant E52Q/F3Y122-β2 were carried out for comparison to the recently published cryo-EM structure of a holo RNR complex. For both mutant combinations, the distance measurements reveal two conformations of 3,5-F2Y731. Remarkably, one conformation is consistent with 3,5-F2Y731 within the H-bond distance to Y356•, whereas the second one is consistent with the conformation observed in the cryo-EM structure. The observations unexpectedly suggest the possibility of a colinear PCET, in which electron and proton are transferred from the same donor to the same acceptor between Y356 and Y731. The results highlight the important role of state-of-the-art EPR spectroscopy to decipher this mechanism.

Investigation of the Nature of Intermolecular Interactions in Tetra(thiocyanato)corrolato-Ag(III) Complexes: Agostic or Hydrogen Bonded?

Tetra(thiocyanato)corrolato-Ag(III) complexes presented here constitute a new class of metallo-corrole complexes. The spectroscopic properties of these complexes are quite unusual and interesting. For example, the absorption spectra of these β-substituted corrolato-Ag(III) complexes are very different from those of the β-unsubstituted corrolato-Ag(III) derivatives. Single-crystal XRD analysis of a representative tetra(thiocyanato)corrolato-Ag(III) derivative reveals C-H···Ag interactions. The C-H···Ag interactions are rarely demonstrated in the crystal lattice of a discrete coordination/organometallic compound. Optimization of the hydrogen positions of the crystal structure discloses the geometrical parameters of the said interaction as a Ag···H distance of 2.597 Å and ∠C-H···Ag of 109.62°. The natural bond orbital analysis provides information about the donor-acceptor orbitals involved in the interactions and their interaction energies. It was observed that the σC-H orbital overlaps with the vacant d-orbital of Ag with an interaction energy of 17.93 kJ/mol. The filled d-orbital of Ag overlaps with the σ*C-H orbital with an interaction energy of 4.79 kJ/mol. The highlights of this work are that the H···Ag distance is outside of the distance range for the typical agostic interaction but fitted with the weak H-bond distance. However, the ∠C-H···Ag angle is within the range of the agostic interaction. Both crystallographic data and electronic structure calculations reveal that these kinds of intermolecular interactions in square-planar d8 Ag(III) complexes are intermediate in nature. Thus, they cannot be categorically called either hydrogen bonding or agostic interaction.

Impact of donor acidity on νC≡N and νO–H spectral shifts in O-H···N≡C H-bonded complexes between nitriles and alcohols: a combined IR spectroscopic and quantum chemical investigation

Twenty-five numbers of O-H···N≡C H-bonded complexes formed between 5 alcohols and 5 nitrile compounds have been studied using IR spectroscopy in room temperature CCl4 solution to elucidate the impact of donor alcohols on the and spectral shifts. The magnitude of blue and red shifts exhibited by and , respectively, upon H-bond formation were found to show an orderly trend with varying H-bond donor; both types of spectral shifts showed a linear dependence on the of the alcohols. Besides, it was also found that both and show a linear correlation between themselves. Quantum chemical calculations carried out at B97D/6-311++G(d,p) level of theory corroborated the experimental results. H-Bond distance scans were also performed to look at the effect of H-bond distance on spectral shift. Furthermore, AIM and NBO analyses have also been performed to support the results. The findings have been compared against 25 numbers of O-H···O=C H-bonded complexes formed between the same 5 alcohols and 5 carbonyl compounds, both experimentally and theoretically. Unlike the red- and blue-shifted donors, different counterpropagating forces were also found to act simultaneously in the case of acceptors to govern the nature of shift.

Rationale Design, Synthesis, and Pharmacological Evaluation of Isatin Analogues as Antiseizure Agents

Background: Epilepsy is one of the most common and devastating neurological diseases affecting about 1% of the world’s population at any time. Herein, we have reported rationale design and synthesis of 5-acetyl-3-((4-substitutedphenyl)imino)indolin-2-one analogues 3(a-k) as antiseizure agents. Objective: These analogues were designed as four component pharmacophoric model by clubbing structural fragments of potent antiepileptic drugs. The Aim of this study is to synthesize structurally designed isatin analogues and screen them for anticonvulsant activity and neurotoxicity. Methods: The compound 3d have exhibited good anticonvulsant activity in preclinical seizure models with better toxicity profile when compared to standard drugs (3d: ED50 = 31.5 mg/kg, MES test; ED50 = 37.4 mg/kg, scPTZ test; TD50 = 384.3 mg/kg,). Compound 3d have also shown good binding affinity at crucial amino acids of GluN1 subunit of NMDAR (Docking score = -9.30) and fit adequately in the cavity of the receptor (Amino acids involved and H-bonding distance = GLY93: acetyl >C=O, 2.38Å; PHE92: acetyl >C=O, 2.22Å; and THR26: >C=O of isatin, 1.71Å). Results of molecular docking supported the structural features present over isatins to persuade potent antiseizure activity. Results: The compound 3d have exhibited good anticonvulsant activity in preclinical seizure models with better toxicity profile when compared to standard drugs (3d: ED50 = 31.5 mg/kg, MES test; ED50 = 37.4 mg/kg, scPTZ test; TD50 = 384.3 mg/kg,). Compound 3d have also shown good binding affinity at crucial amino acids of GluN1 subunit of NMDAR (Docking score = -9.30) and fit adequately in the cavity of the receptor (Amino acids involved and H-bonding distance = GLY93: acetyl >C=O, 2.38Å; PHE92: acetyl >C=O, 2.22Å; and THR26: >C=O of isatin, 1.71Å). Results of molecular docking supported the structural features present over isatins to persuade potent antiseizure activity. Conclusion: Rationale designing strategy, in-vivo pharmacological profile, and computational studies make us anticipate the emergence of these molecules as novel antiseizure agents, which can be further explored to develop probes for the treatment of epilepsy.

Evaluation of hydrogen bonds formation in the selected rare sugars based on 6-31G* and 6-311 + + G(d,p) basis sets.

Rare sugars are monosaccharides with tremendous potential for applications in pharmaceutical, cosmetics, nutraceutical, and flavors industries. The four rare sugars, including gulose, allose, altrose, and talose, are stereoisomers that are different in the hydroxyl group orientation (axial or equatorial) on the C2-4atoms. The basis sets effect in evaluation of the possibility intramolecular hydrogen bonding (H-bonds) in the selected rare sugars was studied from 6-31G* to 6-311 ++ G(d,p) basis sets using DFT, AIM, and NBO methods. The results show that the selected rare sugars are more stable at 6-311 ++ G(d,p) basis sets compared to 6-31G* because their electronic energies were reduced between 158 and 164 (kcal.mol-1). The overall effect of basis set enhancement is to decrease H-bond energies in the range of 1.25 to 2.51 (kcal.mol-1) and stabilization energies between 2 and 5 (kcal.mol-1) in the selected rare sugars at the DFT level of theory. The intramolecular H-bond distances, H-bond energies obtained from the AIM analysis, and alsothe second-order stabilization energies obtained from the NBO analysis were fluctuated largely depending on the basis set. In summary, it was found that the use of 6-311 ++ G(d,p) basis set to be more efficient results in rare sugars geometry than the 6-31G* basis set.

Non-Markovian modeling of protein folding

We extract the folding free energy landscape and the time-dependent friction function, the two ingredients of the generalized Langevin equation (GLE), from explicit-water molecular dynamics (MD) simulations of the α-helix forming polypeptide [Formula: see text] for a one-dimensional reaction coordinate based on the sum of the native H-bond distances. Folding and unfolding times from numerical integration of the GLE agree accurately with MD results, which demonstrate the robustness of our GLE-based non-Markovian model. In contrast, Markovian models do not accurately describe the peptide kinetics and in particular, cannot reproduce the folding and unfolding kinetics simultaneously, even if a spatially dependent friction profile is used. Analysis of the GLE demonstrates that memory effects in the friction significantly speed up peptide folding and unfolding kinetics, as predicted by the Grote-Hynes theory, and are the cause of anomalous diffusion in configuration space. Our methods are applicable to any reaction coordinate and in principle, also to experimental trajectories from single-molecule experiments. Our results demonstrate that a consistent description of protein-folding dynamics must account for memory friction effects.

Water structure around a left-handed Z-DNA fragment analyzed by cryo neutron crystallography.

Even in high-quality X-ray crystal structures of oligonucleotides determined at a resolution of 1 Å or higher, the orientations of first-shell water molecules remain unclear. We used cryo neutron crystallography to gain insight into the H-bonding patterns of water molecules around the left-handed Z-DNA duplex [d(CGCGCG)]2. The neutron density visualized at 1.5 Å resolution for the first time allows us to pinpoint the orientations of most of the water molecules directly contacting the DNA and of many second-shell waters. In particular, H-bond acceptor and donor patterns for water participating in prominent hydration motifs inside the minor groove, on the convex surface or bridging nucleobase and phosphate oxygen atoms are finally revealed. Several water molecules display entirely unexpected orientations. For example, a water molecule located at H-bonding distance from O6 keto oxygen atoms of two adjacent guanines directs both its deuterium atoms away from the keto groups. Exocyclic amino groups of guanine (N2) and cytosine (N4) unexpectedly stabilize waters H-bonded to O2 keto oxygens from adjacent cytosines and O6 keto oxygens from adjacent guanines, respectively. Our structure offers the most detailed view to date of DNA solvation in the solid-state undistorted by metal ions or polyamines.

Theoretical Investigation of Intermolecular Dihydrogen Bonds in C2H2···HM and C2H4···HM (M = Li, Na and K) Complexes: A DFT and ab initio Study

This study aims to investigate the dihydrogen bond formation in ethyne (C2H2) and ethene (C2H4) with alkali metal hydrides (HM; M = Li, Na and K) complexes using density functional theory (DFT) and ab initio methods. It mainly focuses on the comparison of the performances of different functionals of DFT and ab initio method on the intermolecular dihydrogen bonded complexes. The geometrical parameter and energy values agree with the formation of dihydrogen bonds in the complexes. Among the ethyne and ethene complexes, the smallest dihydrogen bond distance was formed by C2H2···HK and C2H4···HK, respectively. The C2H2 is found to form better dihydrogen bond (DHB) with alkali metal hydrides than C2H4. Among all the functionals, M06L was observed to predict shortest H···H bond distance, while M062X the longest. Natural bond orbital (NBO), quantum theory of atom in molecules (QTAIM) along with molecular electrostatic potential (MEP) analysis further confirms the dihydrogen bond formation.

Dynamics of coordination of H3O+ and NH4+ in crown ether cavities.

Crown ethers stand out for their ability to form inclusion complexes with metal cations and positively charged molecular moieties. Hydronium and ammonium interact strongly with crown ethers and potentially modulate their ionophoric activity in protic solvents and physiological environments commonly involved in (bio)technological applications. In this work, Born-Oppenheimer molecular dynamics (BOMD) computations are employed to gain insights into the coordination arrangements of H3O+ and NH4+ in the complexes with the native crown ethers 15-crown-5 (15c5) and 18-crown-6 (18c6). Both cations display dynamic changes in coordination inside the cavities of the crown ethers. On the one hand, hydronium explores different coordination arrangements, through rotation around its C3 axis in the 15c5 complex, and through breathing motions, involving rapid inversions of the O atom along the C3 axis in the 18c6 complex. On the other hand, ammonium undergoes a facile rotation in three dimensional space, leading to frequent changes in the NH bonds involved in the coordination with the crown ether. The reduced host-guest symmetry matching of the 15c5 macrocycle enhances the reorientation dynamics and, in the case of H3O+, it promotes short H-bonding distances yielding events of proton transfer to the crown ether. The infrared vibrational spectra predicted by the BOMD computations within this dynamic framework reproduce with remarkable accuracy the action spectra of the isolated complexes obtained in previous infrared laser spectroscopy experiments. The experimentally observed band positions and broadening can then be rationalized in terms of orientational diffusion of the cations, changes in the coordinating H-bonding pairs sustaining the complex and eventual proton bridge formation.