Hydrogen-bonded Chains Research Articles

Discovery of potent HIV-1 non-nucleoside reverse transcriptase inhibitors by exploring the structure-activity relationship of solvent-exposed regions I.

Two novel series of human immunodeficiency virus-1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs) bearing a thiophene[3,2-d]pyrimidine scaffold and sulfonamide linker in the right wing have been identified, which demonstrated activity against the wild-type (WT) HIV-1 strain in MT-4 cells with inhibitory concentrations ranging from micromolar to submicromolar. Especially, against the mutant strains K103N and E138K, most compounds exhibited more potent activity than against WT HIV-1. Compound 7 (EC50 =0.014, 0.031μM) achieved the most potent activity against the two mutants, being more effective than that of nevirapine (NVP, EC50 =7.572, 0.190μM) and comparable to that of etravirine (ETV, EC50 =0.004, 0.014μM). Molecular docking experiments on the novel analogs have also suggested that the extensive network of main chain hydrogen bonds are important in the binding mode, which may provide valuable insights for further optimization.

Crystal structures of two nickel(II) macrocyclic salts: (5,7,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo-tetra-deca-ne)nickel(II) bis-(perchlorate) monohydrate and (5,7,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo-tetra-deca-ne)nickel(II) dibromide trihydrate.

The crystal structure of the Ni-14 macrocycle salt, (5,7,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo-tetra-deca-ne)nickel(II) bis-(perchlorate) hemihydrate, [Ni(C16H36N4)]2(ClO4)4·H2O, contains two different diasteriomeric macrocyclic cations in the asymmetric unit, one with two NH protons on each side of the cation (Ia), and the other with all four NH protons on the same side (Ib). The crystal structure of the bromide trihydrate salt of the same Ni-14 macrocyclic cation, namely (5,7,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo-tetra-deca-ne)nickel(II) dibromide trihydrate, [Ni(C16H36N4)]Br2·3H2O (II), contains only the same diastereomer as Ib, with the four N-H bonds on the same side. The geometry around the Ni atom differs slightly between the two diastereomeric cations, as the mean Ni-N distance in Ia is 1.952 (2) Å, while that for Ib and II is 1.928 (2) Å. The hexa-methyl substitution in all three macrocyclic cations has the two dimethyl-substituted C atoms cis to one another, different from the trans 5,5,7,12,12,14-hexa-methyl Ni-14 cations found in all but one of the many published crystal structures of hexa-methyl Ni-14 macrocycles. In each of the two crystal structures, the anions, water mol-ecules, and N-H protons of the macrocyclic cations form extensive hydrogen-bonded zigzag chains propagating along [001] in I and [010] in II.

Crystal structure of a host-guest complex of the tris-urea receptor, 3-(4-nitro-phen-yl)-1,1-bis-{2-[3-(4-nitro-phen-yl)ureido]eth-yl}urea, that encapsulates hydrogen-bonded chains of di-hydrogen phosphate anions with separate tetra-n-butyl-ammonium counter-ions.

The title compound, C25H25N9O9·C16H36N+·H2PO4 - (I) or (C25H25N9O9)·(n-Bu4N+)·(H2PO4 -) (systematic name: 3-(4-nitro-phen-yl)-1,1-bis-{2-[3-(4-nitro-phen-yl)ureido]eth-yl}urea tetra-butyl-ammonium di-hydrogen phosphate), comprises a tris-urea receptor (R), a di-hydrogen phosphate anion and a tetra-n-butyl-ammonium cation. It crystallizes with two independent formula units in the asymmetric unit. The conformations of the two tris-urea receptors are stabilized by N-H⋯O and C-H⋯O intra-molecular hydrogen bonds. Each di-hydrogen phosphate anion has two O-H⋯O inter-molecular hydrogen-bonding inter-actions with the other di-hydrogen phosphate anion. Inversion-related di-anion units are linked by further O-H⋯O hydrogen bonds, forming a chain propagating along the a-axis direction. Each di-hydrogen phosphate anion makes a total of four N-H⋯O(H2PO4 -) hydrogen bonds with two ureido subunits from two different tris-urea receptors, hence each tris-urea receptor provides the two ureido subunits for the encapsulation of the H2PO4 - hydrogen-bonded chain. There are numerous inter-molecular C-H⋯O hydrogen bonds present involving both receptor mol-ecules and the tetra-n-butyl-ammonium cations, so forming a supra-molecular three-dimensional structure. One of the butyl groups and one of the nitro groups are disordered over two positions of equal occupancy.

Two Hg(II) complexes of 4-pyridinecarbacylamidophosphates: Synthesis, crystal structures, theoretical studies and in vitro antibacterial evaluation

Two new Hg(II) complexes of 4-pyridinecarbacylamidophosphate ligands, HgCl2(L1)2C1 (L1 = 4-NC5H4C(O)NHP(O)[NHC(CH3)3]2); [Hg(L2)Cl3]−[(L2)H]+C2 (L2 = 4-NC5H4C(O)NHP(O)[NHC5H9]2) were synthesized and characterized on the basis of elemental analysis, IR, UV–Vis, and multinuclear NMR spectroscopy. Molecular structures of C1 and C2 were determined by X-ray crystallography and revealed that coordination of ligands to Hg(II) has occurred from the nitrogen atom of the pyridine ring in neutral (C1) and ionic (C2) metal complexes. Coordination of L1 and L2 from Npyridine, as a monodentate ligand, resulted in infinite 1D and 2D hydrogen-bonded polymeric chains for C1 and C2, respectively. Mass spectral data further support the structure of the compounds and XRD indicates the crystalline state of metal complexes. The intermolecular hydrogen bonding interactions which connected the chains into 3D frameworks in both complexes were supported by Hirshfeld surface analysis and fingerprint plots. Also, natural bond orbital analysis divulges that the metal–ligand interaction in C1 and C2 is the LMCT. By using parameters derived from the quantum theory of atoms in molecules, the nature of Hg-ligand interaction is found to be mainly electrostatic with a small amount of covalent character. Hg(II) complexes and the corresponding ligands were also screened for their antibacterial activity against the selected Gram-positive and Gram-negative bacteria. Results indicated that C2 possess strong cytotoxic activity against the tested bacteria with MIC values ranging from 2.79 to 22.32 µg/ml. The activity of compounds was interpreted by their calculated descriptors, density, log P, and the lower unoccupied molecular orbital.

Structural insights into the molecular mechanism underlying Sirt5-catalyzed desuccinylation of histone peptides

Histone modification is a ubiquitous regulatory mechanism involved in a variety of biological processes, including gene expression, DNA damage repair, cell differentiation, and ontogenesis. Succinylation sites on histones have been identified and may have functional consequences. Here, we demonstrate that human sirtuin 5 (Sirt5) catalyzes the sequence-selective desuccinylation of numerous histone succinyl sites. Structural studies of Sirt5 in complex with four succinyl peptides indicate an essential role for the conserved main chain hydrogen bonds formed by the succinyl lysine (0), +1, and +3 sites for substrate-enzyme recognition. Furthermore, biochemical assays reveal that the proline residue at the +1 site of the histone succinylation substrate is unfavorable for Sirt5 interaction. Our findings illustrate the molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5 and provide insights for further studies of the biological functions associated with histone succinylation and Sirt5.

Succinic, fumaric, adipic and oxalic acid cocrystals of promethazine hydrochloride

Novel cocrystals of promethazine hydrochloride [PTZ-Cl; systematic name: N,N-dimethyl-1-(10H-phenothiazin-10-yl)propan-2-aminium chloride] with succinic acid (PTZ-Cl-succinic, C17H21N2S+·Cl-·0.5C4H6O4), fumaric acid (PTZ-Cl-fumaric, C17H21N2S+·Cl-·0.5C4H4O4) and adipic acid (PTZ-Cl-adipic, C17H21N2S+·Cl-·0.5C6H10O4) were prepared by solvent drop grinding and slow evaporation from acetonitrile solution, along with two oxalic acid cocrystals which were prepared in tetrahydrofuran (the oxalic acid hemisolvate, PTZ-Cl-oxalic, C17H21N2S+·Cl-·0.5C2H2O4) and nitromethane (the hydrogen oxalate salt, PTZ-oxalic, C17H21N2S+·C2HO4-). The crystal structures obtained by crystallization from tetrahydrofuran and acetonitrile include the Cl- ion in the lattice structures, while the Cl- ion is missing from the crystal structure obtained by crystallization from nitromethane (PTZ-oxalic). In order to explain the formation of the two types of supramolecular configurations with oxalic acid, the intermolecular interaction energies were calculated in the presence of the two solvents and the equilibrium configurations were determined using density functional theory (DFT). The cocrystals were studied by X-ray diffraction, IR spectroscopy and differential scanning calorimetry. Additionally, a stability test under special conditions and water solubility were also investigated. PTZ-Cl-succinic, PTZ-Cl-fumaric and PTZ-Cl-adipic crystallized having similar lattice parameter values, and showed a 2:1 PTZ-Cl to dicarboxylic acid stoichiometry. PTZ-Cl-oxalic crystallized in a 2:1 stoichiometric ratio, while the structure lacking the Cl atom belongs has a 1:1 stoichiometry. All the obtained crystals exhibit hydrogen bonds of the type PTZ...Cl...(dicarboxylic acid)...Cl...PTZ, except for PTZ-oxalic, which forms bifurcated bonds between the hydrogen oxalate and promethazinium ions, along with an infinite hydrogen-bonded chain between the hydrogen oxalate anions.

Ferroelectric Alkylamide-Substituted Helicene Derivative with Two-Dimensional Hydrogen-Bonding Lamellar Phase.

Alkylamide (-CONHC nH2 n+1)-substituted benzene and its pyrene derivatives have shown a discotic hexagonal columnar liquid-crystalline phase through a one-dimensional (1D) intermolecular N-H···O═ hydrogen-bonding interaction, the direction of which is inverted through the application of an alternate current voltage. The polar hydrogen-bonding chains and dipole inversion reveal a ferroelectric polarization-electric field ( P- E) hysteresis curve. Non-π-planar helicene derivatives bearing two -CONHC14H29 chains also indicate a ferroelectric response. The racemic helicene derivative shows a bilayer lamellar liquid-crystal phase within a temperature range of 330-420 K, whereas there is no liquid crystallinity for the optically active derivative because of the different molecular assembly structure. The racemic phase is constructed through a two-dimensional (2D) N-H···O═ hydrogen-bonding network, which shows ferroelectric P- E hysteresis curves at above 340 K. The collective dipole inversion in the 2D layer contributes to the ferroelectricity in the lamellar phase. The remanent polarization ( Pr) of 11.1 μC cm-2 is about 6 times higher than those of the π-planar benzene- and pyrene-based 1D ferroelectrics. Both the density of the hydrogen-bonding site and the domain orientation in the 2D system are higher than those of the 1D columnar system.

A comparative dielectric spectroscopy investigation of beta-cyclodextrin polymer and carboxymethyl beta-cyclodextrin polymer cross-linked by epichlorohydrin

The β-cyclodextrin polymer (β-CDP) and the carboxymethyl-β-cyclodextrin polymer (CM-β-CDP) cross-linked by epichlorohydrin were investigated by dielectric spectroscopy over the frequency range 0.1–100 kHz in the temperature ranges 132.6–464.8 K and 132.9–500.9 K, respectively. The β-CDP reveals a reversible order-disorder transformation of some normal hydrogen bonds to flip-flop type at Ttrans = 220.1 K, whereas the CM-β-CDP doesn't show any transformation of hydrogen bonds. The ac-conductivity plot of β-CDP (lnσ vs 1/T) shows a linear part obeying the Arrhenius equation in the range 289.8–268.8 K with Eα = 0.71 eV during cooling and 0.77 eV during heating. A deformed bell-shaped curve with maximum values at Ttrans = 222.7 K during cooling and 223.8 K during heating in the range 132.6–268.8 K, is due to the hydrogen-bonded transformation. At 328.9 < T < 407 K the ac-conductivity presents a bell-shaped curve with maximum value located at 363.1 K, revealing a new order-disorder transformation. The breaking and the restoration of more stable hydrogen bonds are confirmed by the temperature variation of relaxation time, as three successive topical maxima with values 8.9 μs (223.8 K), 8.9 μs (307.6 K) and 11.9 μs (369.7 K). Above 407.0 K, lnσ increases linearly according to Arrhenius law with Eα = 0.26 eV because of the newly-formed hydrogen-bonded chains. In the case of CM-β-CDP the lnσ vs 1/T plot reveals two linear regions where the Arrhenius equation is valid. Τhe first in the range 252.3–288.2 K (Eα = 0.28 eV cooling or Εα = 0.33 eV heating) is due to the protons originated from the β-CD hydroxyl groups and water molecules while the second in the range 316–349 K (Eα = 0.78 eV heating) is due to the carboxymethyl moieties dissociation. The relaxation time τ of CM-β-CDP increases from 7.5 μs (132.9 K) to 9.5 μs (285.4 K) and then rapidly reaches the value 11.8 μs at 293.7 K denoting the no breaking of hydrogen bonds. Cole-Cole plots of both samples are presented at selective temperatures.

Directional Intermolecular Interactions for Precise Molecular Design of a High- Tc Multiaxial Molecular Ferroelectric.

Quasi-spherical molecules have recently been developed as promising building blocks for constructing high-performance molecular ferroelectrics. However, although the modification of spherical molecules into quasi-spherical ones can efficiently lower the crystal symmetry, it is still a challenge to precisely arouse a low-symmetric polar crystal structure. Here, by introducing directional hydrogen-bonding interactions in the molecular modification, we successfully reduced the cubic centrosymmetric Pm3̅ m space group of [quinuclidinium]ClO4 at room temperature to the orthorhombic polar Pna21 space group of [3-oxoquinuclidinium]ClO4. Different from the substituent groups of -OH, -CH3, and ═CH2, the addition of a ═O group with H-acceptor to [quinuclidinium]+ forms directionally N-H···O═C hydrogen-bonded chains, which plays a critical role in the generation of polar structure in [3-oxoquinuclidinium]ClO4. Systematic characterization indicates that [3-oxoquinuclidinium]ClO4 is an excellent molecular ferroelectric with a high Curie temperature of 457 K, a large saturate polarization of 6.7 μC/cm2, and a multiaxial feature of 6 equiv ferroelectric axes. This work demonstrates that the strategy of combining quasi-spherical molecule building blocks with directional intermolecular interactions provides an efficient route to precisely design new eminent molecular ferroelectrics.

Understanding the effect of nanoconfinement on the structure of water hydrogen bond networks.

Using an integrated approach of network theory and atomistic molecular dynamics simulations, we performed a detailed topological analysis on hydrogen bond networks of water confined between either two graphene sheets or two lipid bilayers to explore the structural perturbation of these networks under nanoscale confinement. The hydrogen bond network structure can be perturbed to a considerable extent when water is confined by such surfaces, yet no small-world behaviour is observed. The presence of ions also reduces the network complexity but its effect may be small depending on the type of confining surfaces. We developed an information flow model to evaluate the fluctuating nature of hydrogen bond networks and to characterise the dynamic, long-distance hydrogen-bonded chains in water. We found that the length and directionality of the hydrogen bond "trails" are highly susceptible to the type of confining surfaces and the degree of confinement. In particular, the endpoints of the hydrogen bond trails are not completely random in confined water, in which inherent distributions are determined by the density of water and the density of hydrogen bonds. This work forms the basis for the study of the pure effect of hydrogen bond network topology on various transport processes, such as proton transfer, that occur along a sequence of hydrogen bonds in a biochemical system. Our results suggest that a combined effect of the structure and lifetime of the hydrogen bond network of interfacial water may contribute to high lateral proton diffusivity at the surface of a lipid membrane.

Crystal structure of (RS)-4-(3-carb-oxy-1-ethyl-6,8-di-fluoro-4-oxo-1,4-di-hydro-quinolin-7-yl)-2-methyl-piperazin-1-ium 3-carb-oxy-5-fluoro-benzoate.

In the title organic salt, C17H20F2N3O3 +·C8H4FO4 -, proton transfer leads to one protonated lomefloxacin mol-ecule (HLf+) and one 3-carb-oxy-5-fluoro-benzoate (5-F-Hip-) anion in the asymmetric unit. The HLf+ cation is bent, with a dihedral angle of 38.3 (1)° between the quinoline ring and the piperazinium moiety. In the crystal, two kinds of N-H⋯O and O-H⋯O hydrogen-bonded chains cross-link each other to produce a three-dimensional network structure that is additionally stabilized by weak C-H⋯O and C-H⋯F hydrogen bonds, as well as π-π inter-actions. The methyl group attached to the piperazinium ring is disordered over two sets of sites [refined ratio: 0.645 (5):0.335 (5)], indicating the presence of both enanti-omers of the cation in the structure.

Synthesis and crystal structures of some bis(3-methyl-1H-indol-2-yl)(salicyl)methanes.

Four 2,2'-bisindolylmethanes (BIMs), a useful class of polyindolyl species joined to a central carbon, were synthesized using salicylaldehyde derivatives and simple acid catalysis; these are 2-[bis(3-methyl-1H-indol-2-yl)methyl]-6-methylphenol, (IIa), 2-[bis(3-methyl-1H-indol-2-yl)methyl]-4,6-dichlorophenol, (IIb), 2-[bis(3-methyl-1H-indol-2-yl)methyl]-4-nitrophenol, (IIc), and 2-[bis(3-methyl-1H-indol-2-yl)methyl]-4,6-di-tert-butylphenol, (IId). BIMs (IIa) and (IIb) were characterized crystallographically as the dimethyl sulfoxide (DMSO) disolvates, i.e. C26H24N2O·2C2H6OS and C25H20Cl2N2O·2C2H6OS, respectively. Both form strikingly similar one-dimensional hydrogen-bonding chain motifs with the DMSO solvent molecules. BIM (IIa) packs into double layers of chains whose orientations alternate every double layer, while (IIb) forms more simply packed chains along the a axis. BIM (IIa) has a remarkably long c axis.

New Copper(II) Coordination Compounds Assembled from Multifunctional Pyridine-Carboxylate Blocks: Synthesis, Structures, and Catalytic Activity in Cycloalkane Oxidation.

Two new copper(II) coordination compounds, namely a 1D coordination polymer [Cu(µ-cpna)(phen)(H2O)]n (1) and a discrete tetracopper(II) derivative [Cu(phen)2(H2O)]2[Cu2(µ-Hdppa)2(Hdppa)2] (2), were hydrothermally synthesized from copper(II) chloride as a metal source, 5-(4-carboxyphenoxy)nicotinic acid (H2cpna) or 5-(3,4-dicarboxylphenyl)picolinic acid (H3dppa) as a principal building block, and 1,10-phenanthroline (phen) as a crystallization mediator. Compounds 1 and 2 were isolated as air-stable microcrystalline solids and fully characterized by elemental and thermogravimetric analyses, IR spectroscopy, powder and single-crystal X-ray diffraction. In the solid state, the structure of 1 discloses the linear interdigitated 1D coordination polymer chains with the 2C1 topology. The crystal structure of an ionic derivative 2 shows that the mono- and dicopper(II) units are extended into the intricate 1D hydrogen-bonded chains with the SP 1-periodic net (4,4)(0,2) topology. Thermal stability and catalytic properties of 1 and 2 were also investigated. In fact, both Cu derivatives act as efficient homogeneous catalysts (catalyst precursors) for the mild oxidation of cycloalkanes by hydrogen peroxide to give the corresponding alcohols and ketones; the substrate scope and the effects of type and amount of acid promoter as well as bond-, regio-, and stereo-selectivity features were investigated.

Agglomeration-resistant 2D nanoflakes configured with super electronic networks for extraordinary fast and stable sodium-ion storage

The promising 2D materials for sodium ion battery always suffer from dramatically sluggish electronic and ionic transport due to the irreversible agglomeration phenomenon. In order to tackle this problem, ethylene glycol is adopted in this work as a soft template in directing the growth of 2D structure based on the chelating ability and hydrogen-bonding chains. Subsequently, ethylene glycol could be in-situ transformed into carbon super electronic networks after the thermal treatment, to dramatically enhance the electrical conductivity and prevent the agglomeration of 2D sheets. Since the highly dispersed nanoflake structures and super electronic network could offer nano-sized effects and ultrashort ion-transport paths, the agglomeration-resistant Na3V2(PO4)3 (NVP) nanoflake displays exciting rate capabilities (about 71.2 mAh g−1 at 200 C, and 56.2 mAh g−1 at the ultrahigh rate of 300 C) and ultralong lifecycles. Our results suggest the potential application of 2D nano-structured NVP cathodes for transportation and large-scale grid storage.

Peculiarities of supramolecular organization of cyclic ketones with vinylacetylene fragments.

1,5-Diaryl(heteroaryl)pentenynones show a tendency to crystallize in acentric space groups due to their inclination to form C-H...O hydrogen-bonded chains instead of dimers and thus exhibit nonlinear optical properties. A series of symmetrical α,α'-bis(3-arylprop-2-yn-1-ylidene)cycloalkanones and unsymmetrical α-(furan-2-ylmethylene)-α'-(3-arylprop-2-yn-1-ylidene)cyclohexanones closely related to pentenynones was synthesized, namely 2,5-bis(3-phenylprop-2-yn-1-ylidene)cyclopentanone, C23H16O, 2,5-bis[3-(4-bromophenyl)prop-2-yn-1-ylidene]cyclopentanone, C23H14Br2O, 2,6-bis(3-phenylprop-2-yn-1-ylidene)cyclohexanone, C24H18O, 2,6-bis[3-(4-bromophenyl)prop-2-yn-1-ylidene]cyclohexanone, C24H16Br2O, 4-tert-butyl-2,6-bis(3-phenylprop-2-yn-1-ylidene)cyclohexanone, C28H25O, 4-tert-butyl-2,6-bis[3-(4-methylphenyl)prop-2-yn-1-ylidene]cyclohexanone, C30H30O, 2-(furan-2-ylmethylene)-6-(3-phenylprop-2-yn-1-ylidene)cyclohexanone, C20H16O2, and 6-(3-butylprop-2-yn-1-ylidene)-2-(furan-2-ylmethylene)cyclohexanone, C10H20O2, and investigated by means of X-ray diffraction to understand peculiarities of their supramolecular organization. Four of the eight novel compounds crystallize in acentric space groups. Three of these four compounds contain substituents at the para position of the phenyl ring, which affect the charge density on the H(CPh) atoms and thus stabilize CPh-H...O interactions. The fourth compound realizes the C-H...O hydrogen bonding via H atoms of the furyl ring. The applicability and shortcomings of the Full Interaction Map tool to predict the likelihood of C-H...O and C-H...Br hydrogen-bonded motifs, and the effect of substituents on the phenyl ring on the supramolecular architecture are discussed.

Hydrogen-bonding chain and dimer motifs in pyridinium and morpholinium hydrogen oxalate salts.

We present here three compounds consisting of pyridinium or morpholinium hydrogen oxalates, each displaying different hydrogen-bonding motifs, resulting in chains for 4-(di-methyl-amino)-pyridinium hydrogen oxalate 0.22-hydrate, C7H11N2 +·C2HO4 -·0.22H2O (1), dimers for 4-tert-butyl-pyridinium hydrogen oxalate, C9H14N+·C2HO4 - (2), and chains for morpholin-ium hydrogen oxalate, C4H10NO+·C2HO4 - (3).

Two polymorphic forms of the oxathiin systemic fungicide active carboxine.

Two polymorphic crystal forms of the title compound, C12H13NO2S (systematic name: 6-methyl-N-phenyl-2,3-di-hydro-1,4-oxathiine-5-carboxamide), were isolated from a truncated, (12 solvent), polymorph screen on pure lyophillized material. Crystals of form 1 were obtained from all solvents included in the screen with the exception of methanol. As isolated from aceto-nitrile the crystals are triclinic, space group P with Z' = 2. Crystals of form 2, which were isolated from methanol only are monoclinic, space group I2/a with Z' = 1. The crystal packing in both structures is dominated by the formation of infinite -NH⋯O hydrogen-bonded chains through the carboxamide core.

Effects of an Interchain Disulfide Bond on Tropomyosin Structure: A Molecular Dynamics Study.

Tropomyosin (Tpm) is a coiled-coil actin-binding dimer protein that participates in the regulation of muscle contraction. Both Tpm chains contain Cys190 residues which are normally in the reduced state, but form an interchain disulfide bond in failing heart. Changes in structural and functional properties of Tpm and its complexes with actin upon disulfide cross-linking were studied using various experimental methods. To understand the molecular mechanism underlying these changes and to reveal the possible mechanism of the involvement of the cross-linking in heart failure, molecular dynamics (MD) simulations of the middle part of Tpm were performed in cross-linked and reduced states. The cross-linking increased bending stiffness of Tpm assessed from MD trajectories at 27 °C in agreement with previous experimental observations. However, at 40 °C, the cross-linking caused a decrease in Tpm stiffness and a significant reduction in the number of main chain hydrogen bonds in the vicinity of residues 133 and 134. These data are in line with observations showing enhanced thermal unfolding of the least stable part of Tpm at 30–40 °C and accelerated trypsin cleavage at residue 133 at 40 °C (but not at 27 °C) upon cross-linking. These results allow us to speculate about the possible mechanism of involvement of Tpm cross-linking to heart failure pathogenesis.

Crystal structure, interaction energies and experimental electron density of the popular drug ketoprophen.

The crystal and molecular structure of the pure (S)-enantiomer of the popular analgesic and anti-inflammatory drug ketoprophen (α-ket) is reported. A detailed aspherical charge-density model based on high-resolution X-ray diffraction data has been refined, yielding a high-precision geometric description and classification of the O-H⋯O interactions as medium strength hydrogen bonds. The crystal structure of the racemic form of ketoprophen (β-ket) was also redetermined at 100 K, at 0.5 Å resolution. A previously unreported disorder (10% occupancy) was discovered. In contrast to the racemic β-ket case, the (S)-enantiomer crystallizes with two independent molecules in the asymmetric unit with two distinct conformations. The major difference between the β-ket and α-ket crystal forms lies in the formation of distinct hydrogen-bonded motifs: a closed ring motif in β-ket versus infinite chains of hydrogen bonds in the chiral α-ket structure. However, the overall crystal packing of both forms is surprisingly similar, with close-packed layers of antiparallel-oriented benzo-phenone moieties bound by C-H⋯π interactions. Notably, the most important stabilizing term in the total lattice energies in both instances proved to be the dispersion related to these interactions. Both forms of the title compound (α- and β-ket) were additionally characterized by differential scanning calorimetry and thermogravimetric analysis.

The first spontaneous resolution of a sulfoxide: Dianin's compound analogue, (R)-4-(4-hy-droxy-phen-yl)-2,2,4-tri-methyl-thia-chroman-1-oxide.

The title sulfoxide, C18H20O2S, was prepared by controlled oxidation of thia-Dianin's compound using hydrogen peroxide in glacial acetic acid. On recrystallization from glacial acetic acid, it was found to form unsolvated, spontaneously resolved crystals, the initial crystal structure analysis revealing the presence of both sulfoxide epimers in the crystal. On multiple recrystallization a single epimer was observed, with crystallization occurring in the unchanged ortho-rhom-bic space group P212121, with Z' = 1. The mol-ecule possesses a distal conformation, referring to the juxtaposition of the p-hydoxyphenyl substituent with respect to its syn-related methyl group, with the sulfoxide oxygen atom anti to the aromatic substituent. The mol-ecular packing features O-H⋯O hydrogen bond chains running parallel to the b axis of the unit cell.