Strong H-bonds Research Articles

Computational and biological studies of novel thiazolyl coumarin derivatives synthesized through Suzuki coupling

The current investigation presents the synthesis, computational molecular-docking and biological activity studies of arylated thiazole coumarins. Aryl substituted thiazolyl coumarin derivatives were synthesized via Suzuki cross-coupling reaction. A detailed reaction condition optimization revealed that the Pd-PEPPSI-IPent precatalyst in only 2 mol% loading resulted in the desired product with high yield. The aim of this study was to examine the antimicrobial behavior of thiazole coumarin derivatives through in vitro and in silico studies. All the compounds showed activity against both antibacterial strains, Staphylococcus aureus and Escherichia coli, except 5d . Similarly, the compounds 5a , 5b , and 5d were found to be active against Trichoderma harzianum. The compound 5d of this series was found to have a higher activity with MIC 125 mg/ml against Trichoderma harzianum. Molecular studies showed the high activities of these compounds are due to the presence of strong H-bonding and π-π interaction with their respective targets. A good correlation was observed between computational and in vitro studies.

Extended H-Bonding through Protic Ionic Liquids Facilitates the Growth and Stability of Water Domains in Hydrophobic Environment.

Discrete water domains in hydrophobic environment find relevance in aerosols, oil refinery, the human body, etc. The interfacial microstructure plays a crucial role in the stability of such water domains. Over the decades, the amphiphile-induced electrostatic interaction is considered to be the major stabilizing factor operating at these interfaces. Here we take the representative water/AOT/oil microemulsion to show that creating a strong H-bonding network through suitable additive, such as protic ionic liquid (IL) at the interface, helps both the growth and stability of water domains in the hydrophobic phase. On the other hand, common electrolytes and aprotic ILs fail to replicate such behavior as seen by Raman, Fourier transform infrared spectroscopy, dynamic light scattering (DLS), and electron microscopy measurements. Experimental results are further supported by the all-atomic molecular dynamics (MD) simulations that showed extended H-bonding mediated by the protic IL cations that were localized at the interface. High temperature DLS and rheology studies have shown greater thermal stability and mechanical strengths of our biocompatible microemulsions, which have potential to become suitable templates for in situ synthesis of nanoparticle and various organic compounds.

Hydrogen-bond network in liquid methanol as studied by neutron Scattering, DFT calculations and molecular dynamics simulations

Neutron scattering experiments were carried out on fully deuterated liquid methanol at room temperature and atmospheric pressure. Experimental data were analyzed to drive the structure factor SM(q), the molecular form factor F1(q) and the intermolecular pair correlation function gL(r). DFT calculation using the 6-311++ G(d, p) basis set was conducted to optimize some possible methanol H-bonded clusters: one dimer, two trimers and two tetramers that may describe the intermolecular arrangement in the liquid. Natural bond orbital (NBO) and atoms-in molecules (AIM) analyses have been performed to characterize the hydrogen-bond interactions in the more probable arrays in the liquid. MD simulations are performed using KBFF and OPLS-AA rigid and flexible potentials. Theoretical results fairly agree with experimental ones and clearly highlight the strong H-bond between methyl and hydroxyl groups.

Intra- and inter-molecular interactions in choline-based ionic liquids studied by 1D and 2D NMR

Choline acetate [Ch]+[OAc]− and choline trifluoroacetate [Ch]+[TFA]− mixed with 30 wt% H2O have been characterized by variable temperature 1D and 2D 1H/19F NMR. It was found that the cation, anion and water molecules participate in a strong local H-bond network, but there was no evidence for the formation of large clusters of ions. Weaker association effects were observed for the trifluoroacetate than for the acetate, originating from the higher anion acidity of TFA. Rotational correlation times, which were extracted by temperature dependent spin-lattice relaxation measurements, indicated that cations, anions and H2O exhibit collective reorientation even at room temperature. At the same time, no significant long-range correlations in the translational motion of the ions could be observed from PFG diffusion measurements. Moreover, 1D and 2D NOE experiments showed that both ions share close proximity to water molecules for a period on the order of 0.2 s at room temperature. It is deduced that the ions exist in a solvent-shared ion pair (SIP) configuration, with strongly correlated short-range dynamics between the choline cation and the H2O molecules, indicating a similar behavior of these ILs to a deep eutectic solvent with water as Lewis acid. A reason for this observation, which is supported by a high entropy term in the activation process particularly at low temperatures, could be a fairly static configuration with water near the –N(CH3)3 center of the choline, and relaxation caused by pseudorotation due to reordering of the H-bond network.

COMPETITION BETWEEN METHANOL AND WATER MOLECULES UPON THE FORMATION AND SOLVATION OF IONS IN THE CH3OH–H2O–HCl SYSTEM

IR spectroscopy and density functional theory (B3LYP/6-31++G(d, p)) are used to study the competition between methanol and water molecules during the formation of (CH3(H)O∙∙∙H∙∙∙O(H)CH3)+, (CH3(H)O∙∙∙H∙∙∙OH2)+, and (H2O∙∙∙H∙∙∙OH2)+ ions with strong quasi-symmetrical H-bonds and their solvation in the CH3OH–H2O–HCl system. When water is added to a solution of HCl in methanol, H2O molecules substitute CH3OH molecules in (CH3(H)O∙∙∙H∙∙∙O(H)CH3)+ ions to form mixed disolvates. Conversely, when methanol is added to an aqueous solution of HCl, (H2O∙∙∙H∙∙∙OH2)+ ions are maintained and CH3OH molecules are involved in their solvation. Provided that the fractions of methanol and water are commensurate, the solutions contain simultaneously (CH3(H)O∙∙∙H∙∙∙OH2)+ and (H2O∙∙∙H∙∙∙OH2)+ ions. The ratio between their concentrations depends on the content of HCl in the system. It is shown that the energy of the hydrogen bond system per one dissociated HCl molecule is the main factor determining the structure of CH3OH–H2O–HCl solutions, in particular, the composition of proton disolvates.

Energetic and Structural Studies of Two Biomass-Derived Compounds: 6- and 7-hydroxy-1-indanones

The energetic study of 6-hydroxy-1-indanone and 7-hydroxy-1-indanone was performed using experimental techniques and computational calculations. The enthalpies of combustion and sublimation of the two compounds were determined and allowed to derive the corresponding gas-phase standard molar enthalpies of formation. For this purpose, static-bomb combustion calorimetry and drop-method Calvet microcalorimetry were the experimental techniques used. Further, the enthalpy of fusion of each compound was obtained from scanning differential calorimetry measurements. Additionally, the gas-phase standard molar enthalpies of formation of these compounds were calculated through high-level ab initio calculations. The computational study of the molecular structures of the indanones was carried out and two possible conformers were observed for 6-hydroxy-1-indanone. Furthermore, the energetic effects associated with the presence of one hydroxyl group as a substituent on the benzenic ring of 1-indanone were also evaluated. Both experimental and theoretical methods show that 7-hydroxy-1-indanone is thermodynamically more stable than the 6-isomer in the gaseous phase and these results provide evidence for the existence of a strong intramolecular H-bond in 7-hydroxy-1-indanone. Finally, the intramolecular proton transfer in 7-hydroxy-1-indanone has been evaluated and as expected, it is not energetically favorable.

Interconvertible Hydrochlorothiazide–Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue

The design of new multicomponent pharmaceutical materials that involve different active pharmaceutical ingredients (APIs), e.g., drug-drug cocrystals, is a novel and interesting approach to address new therapeutic challenges. In this work, the hydrochlorothiazide-caffeine (HCT–CAF) codrug and its methanol solvate have been synthesized by mechanochemical methods and thoroughly characterized in the solid state by powder and single crystal X-ray diffraction, respectively, as well as differential scanning calorimetry, thermogravimetric analyses and infrared spectroscopy. In addition, solubility and stability studies have also been performed looking for improved physicochemical properties of the codrug. Interestingly, the two reported structures show great similarity, which allows conversion between them. The desolvated HCT–CAF cocrystal shows great stability at 24 h and an enhancement of solubility with respect to the reference HCT API. Furthermore, the contribution of intermolecular forces on the improved physicochemical properties was evaluated by computational methods showing strong and diverse H-bond and π–π stacking interactions.

Structural diversity from co-crystal to 1D coordination polymers of 2,6-naphthalenedicarboxylic acid with 4,4′-bipyridine as coligand: structural and computational approach

The co-crystal 2,6-naphthalenedicarboxylic acid (2,6-NDCA) and 4,4′-bipyridine (4,4′-bipy) I and metal (Li+) complex of 2,6-NDCA with 4,4′-bipy i.e. {[Li(2,6-NDC)0.5.(H2O)2] n .4,4′-bipy} II (2,6-NDC = 2,6-naphthalenedicarboxyle) have been characterized by single crystal X-ray diffraction, IR spectra, elemental, and TGA analyses. The co-crystals are stabilized by strong H-bonding between acid–base units whereas the Li+ ion based mixed complex is stabilized by both coordination and H-bonding interactions. During investigation of strong or weak intermolecular interactions, X-ray diffraction analysis and Hirshfeld surface analysis gave rise to comparable results but in the Hirshfeld surface analysis, two-third times more close contacts were observed. Thermogravimetry shows that the complex is stable up to 200 °C after the removal of coordinated water molecules. To get some insights in the chemical reactivity indices, the HOMO-LUMO gap, chemical potential, chemical hardness, and electrophilicity indices for both systems (in gas phase) have been analyzed on the basis of theoretical investigations along with their molecular electrostatic potential surfaces and the total electron density plots; I has been found to be more stable than II which appears to be because of the strong H-bonding interaction(s). The fingerprint plots demonstrate that these weak nonbonding interactions are important for stabilizing the crystal packing.

Adsorption of pharmaceuticals from aqueous solutions using biochar derived from cotton gin waste and guayule bagasse

Biochars produced from cotton gin waste (CG) and guayule bagasse (GB) were characterized and explored as potential adsorbents for the removal of pharmaceuticals (sulfapyridine-SPY, docusate-DCT and erythromycin-ETM) from aqueous solution. An increase in biochar pyrolysis temperature from 350 οC to 700 οC led to an increase in pH, specific surface area, and surface hydrophobicity. The electronegative surface of all tested biochars indicated that non-Coulombic mechanisms were involved in adsorption of the anionic or uncharged pharmaceuticals under experimental conditions. The adsorption capacities of Sulfapyridine (SPY), Docusate (DCT) and Erythromycin (ETM) on biochar were influenced by the contact time and solution pH, as well as biochar specific surface area and functional groups. Adsorption of these pharmaceutical compounds was dominated by a complex interplay of three mechanisms: hydrophobic partitioning, hydrogen bonding and π–π electron donor–acceptor (EDA) interactions. Despite weaker π–π EDA interactions, reduced hydrophobicity of SPY− and increased electrostatic repulsion between anionic SPY− and the electronegative CG biochar surface at higher pH, the adsorption of SPY unexpectedly increased from 40% to 70% with an increase in pH from 7 to 10. Under alkaline conditions, adsorption was dominated by the formation of strong negative charge-assisted H-bonding between the sulfonamide moiety of SPY and surface carboxylic groups. There seemed to be no appreciable and consistent differences in the extent of DCT and ETM adsorption as the pH changed. Results suggest the CG and GB biochars could act as effective adsorbents for the removal of pharmaceuticals from reclaimed water prior to irrigation. High surface area biochars with physico-chemical properties (e.g., presence of functional groups, high cation and anion exchange capacities) conducive to strong interactions with polar-nonpolar functionality of pharmaceuticals could be used to achieve significant contaminant removal from water.Graphic

Synthesis, Infrared and Molecular Structure of Adamantane-1-Ammonium Picrate Monohydrate: A Derivative of the Antiviral Symmetrel

The synthesis, infrared, and crystal structure investigations of adamantane-1-ammonium picrate monohydrate, (C10H21N)(C6H2N3O7) ⋅ H2O, were performed. The title compound crystallizes in the space group P21/n with the monoclinic unit cell parameters: a = 12.7211(9) A, b = 6.8233(4) A, c = 21.4130(14) A and β = 105.950(7)°, V = 1787.1(2) A3, Z = 4. The asymmetric unit of the studied compound consists of one Adamantane-1-ammonium cation, one water and one picrate anion with two disordered nitro groups. The molecules are connected by strong H-bonds. As can be seen, the ionic pair is linked through two bifurcate N–H⋅⋅⋅O hydrogen bonds, identified as N1–H1A⋅⋅⋅O1 and N1–H1A⋅⋅⋅O2, to form a dimer. Also, water molecule acts bridging two picrate molecules connected by O1w–H1w⋅⋅⋅O1 and O1w–H2w⋅⋅⋅O4. These interactions form an infinite chain extended along the [101] direction. Finally, the main intermolecular contacts were analyzed based on Hirshfeld surfaces and their fingerprint plot.

Molecular dynamics simulations of sulfone derivatives in complex with DNA topoisomerase IIα ATPase domain

Human topoisomerase II alpha (TopoIIα) is a crucial enzyme involved in maintaining genomic integrity during the process of DNA replication and mitotic division. It is a vital therapeutic target for designing novel anticancer agents in targeted cancer therapy. Sulfones, members of organosulfur compounds, have been reported to possess various biological activities such as antimicrobial, anti-inflammatory, anti-HIV, anticancer, and antimalarial properties. In the present study, a series of sulfones was selected to evaluate their inhibitory activity against TopoIIα using computational approaches. Molecular docking results revealed that several sulfone analogs bind efficiently to the ATPase domain of TopoIIα. Among them, sulfones 18a, 60a, *4 b, *8 b, *3c, and 8c exhibit higher binding affinity than the known TopoII inhibitor, salvicine. Molecular dynamics simulations and free energy calculations based on MM/PB(GB)SA method demonstrated that sulfone *8 b strongly interacts with amino acid residues in the ATP-binding pocket (E87, N91, D94, I125, I141, F142, S149, G161, and A167), driven mainly by an electrostatic attraction and a strong H-bond formation at G161 residue. Altogether, the obtained results predicted that sulfones could have a high potential to be a lead molecule for targeting TopoIIα. Communicated by Ramaswamy H. Sarma

Computational characterisation of Toxoplasma gondii FabG (3-oxoacyl-[acyl-carrier-protein] reductase): a combined virtual screening and all-atom molecular dynamics simulation study

Toxoplasma gondii is an opportunistic obligate parasite, ubiquitous around the globe with seropositivity rates that range from 10% to 90% and infection by the parasite of pregnant women causes pre-natal death of the foetus in most cases and severe neurodegenerative syndromes in some. No vaccine is currently available, and since drug-resistance is common among T. gondii strains, discovering lead compounds for drug design using diverse tactics is necessary. In this study, the sole constituent isoform of an enzymatic 3-oxoacyl-[acyl-carrier-protein] reduction step in an apicoplast-located fatty acid biosynthesis pathway was chosen as a possible drug target. FASII is prokaryotic therefore, targeting it would pose fewer side-effects to human hosts. After a homology 3D modelling of TgFabG, a high-throughput virtual screening of 9867 compounds, the elimination of ligands was carried out by a flexible ligand molecular docking and 200 ns molecular dynamics simulations, with additional DCCM and PC plot analyses. Molecular Dynamics and related post-MD analyses of the top 3 TgFabG binders selected for optimal free binding energies, showed that L2 maintained strong H-bonds with TgFabG and facilitated structural reorientation expected of FabGs, namely an expansion of the Rossmann Fold and a flexible lid capping. The most flexible TgFabG sites were the α7 helix (the flexible lid region) and the β4-α4 and β5-α6 loops. For TgFabG-L2, the movements of these regions toward the active site enabled greater ligand stability. Thus, L2 ("Skimmine"; PubChem ID: 320361), was ultimately selected as the optimal candidate for the discovery of lead compounds for rational drug design. Communicated by Ramaswamy H. Sarma

Microscopic mechanism about the selective adsorption of Cr(VI) from salt solution on O-rich and N-rich biochars

The adsorption of Cr(VI) on biochars can be suppressed by coexisting anions, but the roles of O-containing functional groups and in particular N-containing functional groups are unclear. In this study, we combined spectroscopic and molecular simulation approaches to investigate the selective adsorption of Cr(VI) on the O-rich (PB, UB1) and N-rich (UB3, UB5) biochars under strong competition of anions. The elemental analysis and pyrolysis-gas chromatography/mass spectrometry indicated that the structures of PB and UB1 were similar, and so were the UB3 and UB5. Quantification of functional groups showed that for UB1, 75.3% of Cr(VI) removal was attributed to O-containing groups, while 53.3–72.7% of that was mediated by N-containing groups in UB3 and UB5. X-ray photoelectron spectra and density functional theory calculations confirmed that for O-rich biochars, surface complexation and strong H-bonds between carboxyl/hydroxyl and HCrO4– improved Cr(VI) removal in the presence of anions, while for N-rich biochars, Cr(VI) adsorption was depressed by coexisting anions in the order of Cl–>NO3– >SO42– because of the weaker H-bond between protonated amino groups and HCrO4–. This study presents a novel approach for quantitative, molecular-level evaluation of the roles of biochar functional groups in the Cr(VI) removal from complex environmental systems.

Effect of acceptor and donor doping on the state of protons in block-layered structures based on BaLaInO4

The present work describes the effect of acceptor and donor doping on the state of protons in block-layered proton conductors based on BaLaInO4. It was proved that the increase of the dopant concentration (both Ba2+ and Ti4+) leads to the increase of the amount of water uptake and at the same time to the decrease in the contribution of protons, involved in the strong H-bonds. The main factor determined the increase of concentration of protonic species is not the nature of appeared oxygen defects (oxygen vacancy or oxygen interstitial), but the increase in the unit cell volume during doping.

L-Lysine Amino Acid Adsorption on Zeolite L: a Combined Synchrotron, X-Ray and Neutron Diffraction Study.

Invited for this month's cover are the groups of Annalisa Martucci and Luisa Pasti at the University of Ferrara (Italy). The cover picture shows L-lysine amino acid adsorption on zeolite L. The role of zeolite channels in the stabilization of the lysine absorbed and the effect of water on protein structure are elucidated at atomistic level. The stabilization of the L α-helical conformation is related to strong H-bonds between the tail aminogroups of lysine molecules and the Brønsted acid site as well as to complex intermolecular H-bond system between water molecules, zeolite and amino acid. Read the full text of their Full Paper at 10.1002/open.202000183.

Redox-Responsive H-Bonding: Amplifying the Effect of Electron Transfer Using Proton-Coupled Electron Transfer.

A new strategy to create highly redox-responsive H-bond dimers based on proton-coupled electron transfer is proposed that capitalizes on the importance of secondary H-bonds in determining overall binding strength in H-bond dimers. Electron transfer induced proton transfer across a H-bond can be used to significantly strengthen the overall binding by both creating strong ionic H-bonds and changing the secondary H-bonds from unfavorable to favorable. The viability and potency of this approach are demonstrated with an electroactive DAD (A = H-acceptor, D = H-donor) array, H(MQ+)H, paired with an electroinactive ADA array, O(NH)O. NMR titration of H(MQ+)H with O(NH)O in 0.1 M NBu4PF6/CD2Cl2 gives a Kassoc of 500 M-1, typical of DAD-ADA dimers. However, upon two-electron reduction in 0.1 M NBu4PF6/CH2Cl2, cyclic voltammetry studies indicate a 1.8 × 105 increase in binding strength, corresponding to a very large Kassoc of 9 × 107 M-1. The latter value is typical of DDD-AAA H-bond dimers, consistent with proton transfer across the central H-bond upon reduction.

L-Lysine Amino Acid Adsorption on Zeolite L: a Combined Synchrotron, X-Ray and Neutron Diffraction Study.

Combined neutron and X‐ray powder diffraction techniques highlighted the sorption capacity of the acidic L zeolite towards the L‐lysine amino acid. The role of zeolite channels in the stabilization of the lysine absorbed and the effect of water on protein structure are elucidated at atomistic level. The stabilization of the L α‐helical conformation is related to strong H‐bonds between the tail aminogroups of lysine molecules and the Brønsted acid site as well as to complex intermolecular H‐bond system between water molecules, zeolite and amino acid. This finding is relevant in the catalytic synthesis of polypeptide, as well as in industrial biotechnology by qualitatively predicting binding behaviour

Hydrogen-bonded host\u2013guest systems are stable in ionic liquids

We show that H-bonded host–guest systems associate in ionic liquids (ILs), pure salts with melting point below room temperature, in which dipole–dipole electrostatic interactions should be negligible in comparison with dipole-charge interactions. Binding constants (Ka) obtained from titrations of four H-bonded host–guest systems in two organic solvents and two ionic liquids yield smaller yet comparable Ka values in ionic liquids than in organic solvents. We also detect the association event using force spectroscopy, which confirms that the binding is not solely due to (de)solvation processes. Our results indicate that classic H-bonded host–guest supramolecular chemistry takes place in ILs. This implies that strong H-bonds are only moderately affected by surroundings composed entirely of charges, which can be interpreted as an indication that the balance of Coulombic to covalent forces in strong H-bonds is not tipped towards the former.

Two arsenic capped Dawson-type supramolecular hybrid assemblies induced by benzimidazole for photo-/electro-catalytic performance

Two arsenic capped Dawson arsenomolybdate supramolecular hybrid assemblies, (Cu(biz)2)12[CuI(H2O)2{As0.5IIIAs2MoV2MoVI16O62}2]·2H2O (1) (biz)6(ptz) {AsIII2As2Mo18O62}·H2O (2) (biz ​= ​benzimidazole, ptz ​= ​5-(4-pyridyl)- tetrazole), have been synthesized under hydrothermal condition and fully characterized by routine method. In compound 1, the arsenic-capped {As0.5As2MoV2MoVI16} cluster is bonded to each other by Cu(H2O)2 linker to form a straight chain, which is further extended into 2D waveform layer and 3D supramolecular network with 1D channels via similar supramolecular interaction between O atom of Dawson cluster and N derived from {Cu(biz)2} complex. In compound 2, bi-arsenic capped {AsIII2As2Mo18 O62} cluster is connected to 17 biz and 3 ptz ligands, which are further attracted by 12 Dawson analogues to form a 12-connected 3D supramolecular net with a 324.433.59 topology via strong H-bonds and supramolecular interactions. Compound 2 represents the highest connectivity of bi-arsenic capped Dawson supramolecular assembly. Two compounds show dual-functional electrocatalytic activity for reduction of nitrite and oxidation of dopamine, as well as efficient photocatalytic performances for degradation of intractable dyes under UV irradiation.

Effect of deep eutectic solvent’s characteristics on extraction and bioactivity of polyphenols from Sapodilla pulp

In the present study, a sustainable and efficient deep eutectic solvent (DES)-based ultrasound-assisted extraction method for Sapodilla pulp polyphenols was developed. Seven different DESs prepared using carboxylic acid, polyol and amide were evaluated and compared with an aqueous-organic solvent mixture- acetone–water (50%)- the control used in this study. Low pH and high polarity markedly enhanced the recovery of the polyphenols in acid-based DESs. The highest yield was obtained with oxaline, followed by maloline and laline, as the presence of three OH groups considerably retarded the interaction between DES and target compounds, enhanced the viscosity and reduced the availability of H-bonding sites in glyceline and maline. Although the extraction rate was considerably slower in highly viscous DESs, the time required to attain the equilibrium was only marginally higher for oxaline and maloline than the acetone–water mixture. Reduced air incorporation due to high viscosity and strong H-bonding with DESs also substantially enhanced the storage stability of released antioxidants in DES. The low pH of carboxylic acid constituents and innate toxicity of urea at high concentration were responsible for high antimicrobial activity of acid, and amide-based DES extracts against Aspergillus and Bacillus. However, cell lysis and enzyme inhibitory properties of polyphenols were responsible for antimicrobial activities of polyol-based DESs and organic solvent-based extracts. However, the ability of fungi to metabolize the substrates effectively reduced DESs’ efficiency against the organism compared to bacteria. Therefore, these solvents have great potential as possible alternatives to conventional solvents health-related areas, such as food and medicines.