Stereochemical studies on cyclic peptides: Detailed energy minimization studies on hydrogen bonded all-trans cyclic pentapeptide backbones

Conformational studies have been carried out on hydrogenbonded all-trans cyclic pentapeptide backbone. Application of a combination of grid search and energy minimization on this system has resulted in obtaining 23 minimum energy conformations, which are characterized by unique patterns of hydrogen bonding comprising of β- and γ-turns. A study of the minimum energy conformationsvis-a-vis non-planar deviation of the peptide units reveals that non-planarity is an inherent feature in many cases. A study on conformational clustering of minimum energy conformations shows that the minimum energy conformations fall into 6 distinct conformational families. Preliminary comparison with available X-ray structures of cyclic pentapeptide indicates that only some of the minimum energy conformations have formed crystal structures. The set of minimum energy conformations worked out in the present study can form a consolidated database of prototypes for hydrogen bonded backbone and be useful for modelling cyclic pentapeptides both synthetic and bioactive in nature.

The hydrogen bond: a molecular beam microwave spectroscopist's view with a universal appeal

In this manuscript, we propose a criterion for a weakly bound complex formed in a supersonic beam to be characterized as a `hydrogen bonded complex'. For a `hydrogen bonded complex', the zero point energy along any large amplitude vibrational coordinate that destroys the orientational preference for the hydrogen bond should be significantly below the barrier along that coordinate so that there is at least one bound level. These are vibrational modes that do not lead to the breakdown of the complex as a whole. If the zero point level is higher than the barrier, the `hydrogen bond' would not be able to stabilize the orientation which favors it and it is no longer sensible to characterize a complex as hydrogen bonded. Four complexes, Ar-2-H2O, Ar-2-H2S, C2H4-H2O and C2H4-H2S, were chosen for investigations. Zero point energies and barriers for large amplitude motions were calculated at a reasonable level of calculation, MP2(full)/aug-cc-pVTZ, for all these complexes. Atoms in molecules (AIM) theoretical analyses of these complexes were carried out as well. All these complexes would be considered hydrogen bonded according to the AIM theoretical criteria suggested by Koch and Popelier for C-H center dot center dot center dot O hydrogen bonds (U. Koch and P. L. A. Popelier, J. Phys. Chem., 1995, 99, 9747), which has been widely and, at times, incorrectly used for all types of contacts involving H. It is shown that, according to the criterion proposed here, the Ar-2-H2O/H2S complexes are not hydrogen bonded even at zero kelvin and C2H4-H2O/H2S complexes are. This analysis can naturally be extended to all temperatures. It can explain the recent experimental observations on crystal structures of H2S at various conditions and the crossed beam scattering studies on rare gases with H2O and H2S.

Ab initio molecular dynamics simulations of excited hydrogen halides and methyl halides

Using excited-state ab initio molecular dynamics simulations employing the complete-active-space self-consistent-field approach, we study the mechanism of photodissociation in terms of time evolution of structure, kinetic energy, charges and potential energy for the first excited state of hydrogen halides and methyl halides. Although the hydrogen halides and methyl halides are similar in the photodissociation mechanism, their dynamics are slightly different. The presence of the methyl group causes delay in photodissociation as compared to hydrogen halides.

Trifurcated (four-center) hydrogen bond in solid state crystal structure of 5'-amino-5'-deoxyadenosine p-toluenesulfonate

The crystal structure of 5'-amino-5'-deoxyadenosine (5'-Am.dA) p-toluenesulfonate has been determined by X-ray crystallographic methods. It belongs to the orthorhombic space group P2(1)2(1)2(1) with a = 7.754(3)Angstrom, b = 8.065(1)Angstrom and c = 32.481(2)Angstrom. This nucleoside side shows a syn conformation about the glycosyl bond and C2'-endo-C3'-exo puckering for the ribose sugar. The orientation of N5' atom is gauche-trans about the exocyclic C4'-C5' bond. The amino nitrogen N5' forms a trifurcated hydrogen bond with N3, O9T and O4' atoms. Adenine bases form A.A.A triplets through hydrogen bonding between N6, N7 and N1 atoms of symmetry related nucleoside molecules.

Electrochemical reduction of hydrogen peroxide on stainless steel

Electrochemical reduction of hydrogen peroxide is studied on a sand-blasted stainless steel (SSS)electrode in an aqueous solution of NaClO4.The cyclic voltammetric reduction of H2O2 at low concentrations is characterized by a cathodic peak at -0 center dot 40 V versus standard calomel electrode(SCE).Cyclic voltammetry is studied by varying the concentration of H2O2 in the range from 0 center dot 2 mM to 20 mM and the sweep rate in the range from 2 to 100 mV s(-1)Voltammograms at concentrations of H2O2 higher than 2 mM or at high sweep rates consist of an additional current peak, which may be due to the reduction of adsorbed species formed during the reduction of H2O2. Amperometric determination of H2O2 at -0 center dot 50 V vs SCEprovides the detection limit of 5 A mu M H2O2. A plot of current density versus concentration has two segments suggesting a change in the mechanism of H2O2 reduction at concentrations of H2O2 a parts per thousand yen 2 mM. From the rotating disc electrode study, diffusion co-efficient of H2O2 and rate constant for reduction of H2O2 are evaluated.

Cu2+-induced room temperature hydrogen release from ammonia borane

Mechanical stirring of ammonia borane with CuCl2 in the solid state resulted in the release of hydrogen at room temperature through the intermediacy of [NH4](+)[BCl4](-).

Cytotoxicity of half sandwich ruthenium(II) complexes with strong hydrogen bond acceptor ligands and their mechanism of action

Neutral and cationic organometallic ruthenium(II) piano stool complexes of the type [(eta(6)-cymene)R-uCl(X)(Y)] (complexes R1-R8) has been synthesized and characterized. In cationic complexes, X, Y is either a eta(2) phosphorus ligand such as 1,1-bis(diphenylphosphino)methane (DPPM) and 1,2-bis(diphenylphosphino)ethane (DPPE) or partially oxidized ligands such as 1,2-bis(diphenylphosphino)methane monooxide (DPPMO) and 1,2-bis(diphenylphosphino)ethane monooxide (DPPEO) which are strong hydrogen bond acceptors. In neutral complexes. X is chloride and Y is a monodentate phosphorous donor. Complexes with DPPM and DPPMO ligands ([(eta(6)-cymene)Ru(eta(2)-DPPM)Cl]PF6 (R2), [(eta(6)-cymene)Ru(eta(2)-DPPMO)Cl]PF6 (R3), [(eta(6)-cymene)Ru(eta(1)-DPPM)Cl-2] (R5) and [(eta(6)-cymene)Ru(eta(1)-DPPMO)Cl-2] (R6) show good cytotoxicity. Growth inhibition study of several human cancer cell lines by these complexes has been carried out. Mechanistic studies for R5 and R6 show that inhibition of cancer cell growth involves both cell cycle arrest and apoptosis induction. Using an apoptosis PCR array, we identified the sets of antiapoptotic genes that were down regulated and pro-apoptotic genes that were up regulated. These complexes were also found to be potent metastasis inhibitors as they prevented cell invasion through matrigel. The complexes were shown to bind DNA in a non intercalative fashion and cause unwinding of plasmid DNA in cell-free medium by competitive ethidium bromide binding, viscosity measurements, thermal denaturation and gel mobility shift assays.

Unravelling the self-assembly of hydrogen bonded NDI semiconductors in 2D and 3D

Supramolecular ordering of organic semiconductors is the key factor defining their electrical characteristics. Yet, it is extremely difficult to control, particularly at the interface with metal and dielectric surfaces in semiconducting devices. We have explored the growth of n-type semiconducting films based on hydrogen-bonded monoalkylnaphthalenediimide (NDI-R) from solution and through vapor deposition on both conductive and insulating surfaces. We combined scanning tunneling and atomic force microscopies with X-ray diffraction analysis to characterize, at the submolecular level, the evolution of the NDI-R molecular packing in going from monolayers to thin films. On a conducting (graphite) surface, the first monolayer of NDI-R molecules adsorbs in a flat-lying (face-on) geometry, whereas in subsequent layers the molecules pack edge-on in islands (Stranski–Krastanov-like growth). On SiO2, the NDI-R molecules form into islands comprising edge-on packed molecules (Volmer–Weber mode). Under all the explored conditions, self-complementary H bonding of the imide groups dictates the molecular assembly. The measured electron mobility of the resulting films is similar to that of dialkylated NDI molecules without H bonding. The work emphasizes the importance of H bonding interactions for controlling the ordering of organic semiconductors, and demonstrates a connection between on-surface self-assembly and the structural parameters of thin films used in electronic devices.

Modulating the preferred O-H center dot center dot center dot O hydrogen-bonding motif in a conformationally constrained environment through hydroxy-group derivatization

The crystal structures of three conformationally locked esters, namely the centrosymmetric tetrabenzoate of all-axial per-hydronaphthalene- 2,3,4a, 6,7,8a-hexaol, viz. trans-4a, 8a-dihydroxyperhydronaphthalene-2,3,6,7-tetrayl tetrabenzoate, C38H34O10, and the diacetate and dibenzoate of all-axial perhydronaphthalene-2,3,4a, 8a-tetraol, viz. (2R*,3R*,4aS*,8aS*)-4a, 8a-dihydroxyperhydronaphthalene-2,3-diyl diacetate, C-14-H22O6, and (2R*, 3R*, 4aS*, 8aS*)-4a, 8a-dihydroxyperhydronaphthalene- 2,3-diyl dibenzoate, C24H26O6, have been analyzed in order to examine the preference of their supramolecular assemblies towards competing inter-and intramolecular O-H center dot center dot center dot O hydrogen bonds. It was anticipated that the supramolecular assembly of the esters under study would adopt two principal hydrogen-bonding modes, namely one that employs intermolecular O-H center dot center dot center dot O hydrogen bonds (mode 1) and another that sacrifices those for intramolecular O-H center dot center dot center dot O hydrogen bonds and settles for a crystal packing dictated by weak intermolecular interactions alone (mode 2). Thus, while the molecular assembly of the two crystalline diacyl derivatives conformed to a combination of hydrogen-bonding modes 1 and 2, the crystal packing in the tetrabenzoate preferred to follow mode 2 exclusively.

A direct borohydride fuel cell employing Prussian Blue as mediated electron-transfer hydrogen peroxide reduction catalyst

A direct borohydride-hydrogen peroxide fuel cell employing carbon-supported Prussian Blue (PB) as mediated electron-transfer cathode catalyst is reported. While operating at 30 °C, the direct borohydride-hydrogen peroxide fuel cell employing carbon-supported PB cathode catalyst shows superior performance with the maximum output power density of 68 mW cm−2 at an operating voltage of 1.1 V compared to direct borohydride-hydrogen peroxide fuel cell employing the conventional gold-based cathode with the maximum output power density of 47 mW cm−2 at an operating voltage of 0.7 V. X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray Analysis (EDAX) suggest that anchoring of Cetyl-Trimethyl Ammonium Bromide (CTAB) as a surfactant moiety on carbon-supported PB affects the catalyst morphology. Polarization studies on direct borohydride-hydrogen peroxide fuel cell with carbon-supported CTAB-anchored PB cathode exhibit better performance with the maximum output power density of 50 mW cm−2 at an operating voltage of 1 V than the direct borohydride-hydrogen peroxide fuel cell with carbon-supported Prussian Blue without CTAB with the maximum output power density of 29 mW cm−2 at an operating voltage of 1 V.

Expanding the Peptide beta-Turn in alpha gamma Hybrid Sequences: 12 Atom Hydrogen Bonded Helical and Hairpin Turns

Hybrid peptide segments containing contiguous alpha and gamma amino acid residues can form C-12 hydrogen bonded turns which may be considered as backbone expanded analogues of C-10 beta-turns) found in alpha alpha segments. Exploration of the regular hydrogen bonded conformations accessible for hybrid alpha gamma sequences is facilitated by the use of a stereochemically constrained gamma amino acid residue gabapentin (1-aminomethylcyclohexaneacetic acid, Gpn), in which the two torsion angles about C-gamma-C-beta (theta(1)) and C-beta-C-alpha (theta(2)) are predominantly restricted to gauche conformations. The crystal structures of the octapeptides Boc-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-OMe (1) and Boc-Leu-Phe-Val-Aib-Gpn-Leu-Phe-Val-OMe (2) reveal two distinct conformations for the Aib-Gpn segment. Peptide 1 forms a continuous helix over the Aib(2)-Aib(6) segment, while the peptide 2 forms beta-hairpin structure stabilized by four cross-strand hydrogen bonds with the Aib-Gpn segment forming a nonhelical C-12 turn. The robustness of the helix in peptide 1 in solution is demonstrated by NMR methods. Peptide 2 is conformationally fragile in solution with evidence of beta-hairpin conformations being obtained in methanol. Theoretical calculations permit delineation of the various C-12 hydrogen bonded structures which are energetically feasible in alpha gamma and gamma alpha sequences.

Hybrid peptide design. Hydrogen bonded conformations in peptides containing the stereochemically constrained gamma-amino acid residue, gabapentin

he crystal structure of 12 peptides containing the conformationally constrained 1-(aminomethyl)cyclohexaneacetic acid, gabapentin (Gpn), are reported. In all the 39 Gpn residues conformationally characterized so far, the torsion angles about the C-alpha-C-beta and C-beta-C-gamma bonds are restricted to the gauche conformation (+/- 60 degrees). The Gpn residue is constrained to adopt folded conformations resulting in the formation of intramolecularly hydrogen-bonded structures even in short peptides. The peptides Boc-Ac(6)c-Gpn-OMe 1 and Boc-Gpn-Aib-Gpn-Aib-OMe 2 provide examples of C-7 conformation; peptides Boc-Gpn-Aib-OH 3, Boc-Ac(6)c-Gpn-OH 4, Boc-Val-Pro-Gpn-OH 5, Piv-Pro-Gpn-Val-OMe 6, and Boc-Gpn-Gpn-Leu-OMe 7 provide examples of C-9 conformation; peptide Boc-Ala-Aib-Gpn-Aib-Ala-OMe 8 provides an example of C-12 conformation and peptides Boc-beta Leu-Gpn-Val-OMe 9 and Boc-beta Phe-Gpn-Phe-OMe 10 provide examples of C-13 conformation. Gpn peptides provide examples of backbone expanded mimetics for canonical alpha-peptide turns like the gamma (C-7) and the beta (C-10) turns. The hybrid beta gamma sequences provide an example of a mimetic of the C-13 alpha-turn formed by three contiguous alpha-amino acid residues. Two examples of folded tripeptide structures, Boc-Gpn-beta Phe-Leu-OMe 11 and Boc-Aib-Gpn-beta Phg-NHMe 12, lacking internal hydrogen bonds are also presented. An analysis of available Gpn residue conformations provides the basis for future design of folded hybrid peptides.