Distribution by Scientific Domains
Distribution within Chemistry

Kinds of Conformers

  • anti conformer
  • chair conformer
  • cis conformer
  • different conformer
  • energy conformer
  • low-energy conformer
  • lowest energy conformer
  • planar conformer
  • r conformer
  • stable conformer
  • trans conformer

  • Selected Abstracts

    Reorganization of highly preorganized hosts upon cation complexation: Ab initio study of fluorospherands

    Shabaan A. K. Elroby
    Abstract Fluorospherands (F-spherands) are highly preorganized hosts composed of fluorobenzene or 4-methylfluorobenzene units attached to one another at their 2,6-positions. To understand the intrinsic factors affecting cation complexation, we investigated the complexation behavior between F-spherands and cations using density functional theory (DFT) at the level of B3LYP/6-31G**. The F6-spherand (C6H3F)6, (1) has a highly preorganized spherical cavity, which can encapsulate Li+ and Na+. Its cavity is not big enough for K+ and NH, which prefer external binding. Plausible conformations were studied for F8-spherand (C6H3F)8. Conformer of D2d symmetry (2b) is more stable than that of D4d (2a), in agreement with NMR experiments. The cavity size of F8-spherand is big enough to encapsulate all cations studied. However, the cavity size of 2b is smaller than that of 2a, which resulted in the guest selectivity. Upon complexation, 2b conformation is more stable for Li+ and Na+, while 2a conformation is preferred for larger cations such as K+ and NH. Thus, the ab initio calculations over these highly preorganized fluorospherands give important insights into their host,guest chemistry. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source]

    Analysis of quinazoline and pyrido[2,3- d]pyrimidine N9,C10 reversed-bridge antifolates in complex with NADP+ and Pneumocystis carinii dihydrofolate reductase

    Vivian Cody
    Structural studies of two ternary complexes of Pneumocystis carinii dihydrofolate reductase (pcDHFR) with the cofactor NADP+ and potent antifolates, the N9,C10 reversed-bridge inhibitor 2,4-diamino-6-[N -(2,,5,-dimethoxybenzyl)- N -methyl­amino]quinazoline (1) and its 3,,5,-dimethoxypyrido[2,3- d]pyrimidine analog (2), were carried out. Data for the monoclinic crystals were refined to 1.90,Å resolution for the complex with (1) (R = 0.178) and to 2.1,Å resolution for the complex with (2) (R = 0.193). The effect of the N9,C10 reversed-bridge geometry is to distort the bridge from coplanarity with the pyrido[2,3- d]pyrimidine or quinazoline ring system and to twist the C10 methylene conformation toward a gauche conformation. This change also influences the conformation of the methoxybenzyl ring, moving it away from a trans position. This change places the 5,-methoxy group deeper within the hydrophobic pocket made by Ile65, Pro66 and Phe69 of the pcDHFR active site. These results also revealed the first observation of an unusual conformation for the reversed-bridge geometry (C5,C6,N9,C10 torsion angle) in antifolate (2). The electron density is consistent with the presence of two models (conformers 2-1 and 2-2) that result from inversion of the geometry at N9. The four examples of N9,C10 reversed-bridge antifolates cluster in two conformations, with the structure of quinazoline (1) similar to that previously reported for its 2,,5,-dimethoxypyrido[2,3- d]pyrimidine analog (3). The two conformers of (2) differ from these and each other by a twisted-bridge geometry that results in the dimethoxybenzyl ring occupying the same conformational space. Conformer 2-2 also has the N9,C10 reversed bridge perpendicular to the pyrido[2,3- d]pyrimidine plane, in contrast to the gauche,trans conformation normally observed. As a result of these changes, the N9 methyl probes conformational space in the active site not normally occupied by antifolate structures. The N9 methyl of conformer 2-2 makes close contacts to the conserved Leu25 as well as the hydroxyl O atoms of the nicotinamide ribose and Ser64, whereas the other three reversed-bridge conformers make weak hydrophobic contacts with Ile123, Thr61 and Ile65. These antifolates are ten times more selective for pcDHFR than the C9,N10 bridge parent trimetrexate. However, pyrido[2,3- d]pyrimidines (2) and (3) are three times more selective for pcDHFR than quinazoline (1) is for rat liver DHFR. These data suggest that the loss of hydrogen-bonding interactions with N8 is more important to potency than the interactions of the methoxybenzyl substituents. [source]

    Photochemistry of Salicylaldoxime in Solid Argon: An Experimental and Theoretical Study

    Joanna Grzegorzek
    Abstract The photochemistry of salicylaldoxime in solid argon has been investigated by FTIR spectroscopy and DFT calculations. The salicylaldoxime molecule trapped in the matrix from the vapor above the solid sample has the most stable syn1 conformation with an intramolecular hydrogen bond. Irradiation (, > 320 nm) leads to conversion of the syn1 conformer into the syn3 one, in which the C(H)NOH and (C)OH groups are rotated around the C,C and C,O bonds, respectively, and the intramolecular hydrogen bond is broken. The photochemistry of syn3 involves three possible routes: (i) conversion of syn3 into anti2 conformer, this process requires rearrangement of the NOH group with respect to the C=N bond; (ii) photodissociation of salicylaldoxime into 2-cyanophenol and water, which form a hydrogen-bonded complex; and (iii) regeneration of the syn1 conformer. The third route is a very small contribution to the overall process. The study performed with [D2]salicylaldoxime indicates that the dehydration reaction of salicylaldoxime involves cleavage of the N,O bond and formation of OH and Ph(OH)C(H)N radicals in the first step. Then, the OH radical abstracts a hydrogen atom from the CH group to form 2-cyanophenol and water molecules. When the sample is exposed to the full output of the mercury lamp the 2-cyanophenol complex with water becomes the dominating product. [source]

    Solution structure of a hydrophobic analogue of the winter flounder antifreeze protein

    FEBS JOURNAL, Issue 4 2002
    Edvards Liepinsh
    The solution structure of a synthetic mutant type I antifreeze protein (AFP I) was determined in aqueous solution at pH 7.0 using nuclear magnetic resonance (NMR) spectroscopy. The mutations comprised the replacement of the four Thr residues by Val and the introduction of two additional Lys-Glu salt bridges. The antifreeze activity of this mutant peptide, VVVV2KE, has been previously shown to be similar to that of the wild type protein, HPLC6 (defined here as TTTT). The solution structure reveals an ,,helix bent in the same direction as the more bent conformer of the published crystal structure of TTTT, while the side chain ,1 rotamers of VVVV2KE are similar to those of the straighter conformer in the crystal of TTTT. The Val side chains of VVVV2KE assume the same orientations as the Thr side chains of TTTT, confirming the conservative nature of this mutation. The combined data suggest that AFP I undergoes an equilibrium between straight and bent helices in solution, combined with independent equilibria between different side chain rotamers for some of the amino acid residues. The present study presents the first complete sequence-specific resonance assignments and the first complete solution structure determination by NMR of any AFP I protein. [source]

    Prion domain interaction responsible for species discrimination in yeast [PSI+] transmission

    GENES TO CELLS, Issue 12 2003
    Hideyuki Hara
    Background:, The yeast [PSI+] factor is transmitted by a prion mechanism involving self-propagating Sup35 aggregates. As with mammalian prions, a species barrier prevents prion transmission between yeast species. The N-terminal of Sup35 of Saccharomyces cerevisiae, necessary for [PSI+], contains two species-signature elements,a Gln/Asn-rich region (residues 1,41; designated NQ) that is followed by oligopeptide repeats (designated NR). Results:, In this study, we show that S. cerevisiae[PSI+] is transmissible through plasmid shuffling and cytoplasmic transfer to heterotypic Sup35s whose NQ is replaced with the S. cerevisiae NQ. In addition to homology, the N-terminal location is essential for NQ mediated susceptibility to [PSI+] transmission amongst heterotypic Sup35s. In vitro, a swap of NQ of S. cerevisiae Sup35 led to cross seeding of amyloid formation. Conclusions:, These findings suggest that NQ discriminates self from non-self, and is sufficient to initiate [PSI+] transmission irrespective of whether NR is heterotypic. NR as well as NQ alone coalesces into existing [PSI+] aggregates, showing their independent potentials to interact with the identical sequence in the [PSI+] conformer. The role of NQ and NR in [PSI+] prion formation is discussed. [source]

    N -substituted bis(tetrazol-5-yl)diazenes: Synthesis, spectra, X-ray molecular and crystal structures, and quantum-chemical DFT calculations

    Tatiyana V. Serebryanskaya
    N -Substituted bis(tetrazol-5-yl)diazenes (substituents are 1-CH3 (3a), 1-Ph (3b), 2-CH3 (3c), and 2- tBu (3d)) were synthesized by oxidative coupling of corresponding 5-aminotetrazoles. All compounds were characterized with 1H and 13C NMR, IR- and UV-spectroscopy, and thermal analysis. Crystal and molecular structures of bis(1-phenyltetra- zol-5-yl)diazene (3b) and bis(2- tert -butyltetrazol-5-yl)diazene (3d) were determined by single crystal X-ray diffraction. Molecules of these compounds are trans-isomers in solid. According to X-Ray data, 3b molecule is S-trans-S-trans conformer, however 3d is S-cis-S-cis one. Quantum-chemical investigation of geometry and relative stability of cis- and trans-isomers and stable conformations of compounds 3a,d was carried out. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:24,35, 2010; Published online in Wiley InterScience ( DOI 10.1002/hc.20574 [source]

    Synthesis and conformational study of P -heterocyclic androst-5-ene derivatives

    Éva Frank
    The reactions of (20R)-3,-acetoxy-21-hydroxymethylpregn-5-en-20-ol (2) and (20R)-3,-acetoxypregn-5-ene-20,21-diol (11) with phenylphosphonic dichloride 3 and aryl dichlorophosphates 4,6 afforded novel types of P -heterocyclic androst-5-ene derivatives 7,10 and 12 as epimeric pairs. The diastereomers were separated by column chromatography and were characterized by NMR spectroscopy. Estimation of the stereostructures of the corresponding epimers by B3LYP/631G(d) DFT ab initio calculations suggested that the six-membered hetero ring in compounds 7b and 8a,10a adopts predominantly a chair conformation, with the P -substituents in their preferred orientation. The cyclic phosphonate moiety in 7a or 8b,10b, however, seems to exist as an equilibrium mixture of chair,distorted- boat or chair,chair forms. The theoretical calculations indicate that the conformational equilibrium is shifted toward the distorted- boat conformer for 7a, with a pseudoequatorial P -phenyl substituent, whereas for 8b,10b the chair conformer with an equatorial P -phenoxy group predominates. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:7,14, 2008; Published online in Wiley InterScience ( DOI 10.1002/hc.20372 [source]

    CF3CH(ONO)CF3: Synthesis, IR spectrum, and use as OH radical source for kinetic and mechanistic studies

    M. P. Sulbaek Andersen
    The synthesis, IR spectrum, and first-principles characterization of CF3CH(ONO)CF3 as well as its use as an OH radical source in kinetic and mechanistic studies are reported. CF3CH(ONO)CF3 exists in two conformers corresponding to rotation about the RCONO bond. The more prevalent trans conformer accounts for the prominent IR absorption features at frequencies (cm,1) of 1766 (NO stretch), 1302, 1210, and 1119 (CF stretches), and 761 (ONO bend); the cis conformer contributes a number of distinct weaker features. CF3CH(ONO)CF3 was readily photolyzed using fluorescent blacklamps to generate CF3C(O)CF3 and, by implication, OH radicals in 100% yield. CF3CH(ONO)CF3 photolysis is a convenient source of OH radicals in the studies of the yields of CO, CO2, HCHO, and HC(O)OH products which can be difficult to measure using more conventional OH radical sources (e.g., CH3ONO photolysis). CF3CH(ONO)CF3 photolysis was used to measure k(OH + C2H4)/k(OH + C3H6) = 0.29 ± 0.01 and to establish upper limits of 16 and 6% for the molar yields of CO and HC(O)OH from the reaction of OH radicals with benzene in 700 Torr of air at 296 K. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 159,165, 2003 [source]

    Hydrogen bonding interaction between 1,4-dioxane and water

    Ajay Chaudhari
    Abstract This work reports an interaction of 1,4-dioxane with one, two, and three water molecules using the density functional theory method at B3LYP/6-311++G* level. Different conformers were studied and the most stable conformer of 1,4-dioxane-(water)n (n = 1,3) complex has total energies ,384.1964038, ,460.6570694, and ,537.1032381 hartrees with one, two, and three water molecules, respectively. Corresponding binding energy (BE) for these three most stable structures is 6.23, 16.73, and 18.11 kcal/mol. The hydrogen bonding results in red shift in OO stretching and CC stretching modes of 1,4-dioxane for the most stable conformer of 1,4-dioxane with one, two, and three water molecules whereas there was a blue shift in CO symmetric stretching and CO asymmetric stretching modes of 1,4-dioxane. The hydrogen bonding results in large red shift in bending mode of water and large blue shift in symmetric stretching and asymmetric stretching mode of water. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [source]

    Conformational analysis for some nonclassical antagonists of histamine H3 receptor

    Ana Borota
    Abstract A conformational search in vacuum for a series of 1,3-substituted pyrrolidine derivatives has been performed using the AMBER, AM1, PM3, and MNDO methods. Conformational analysis of the pyrrolidine ligands suggests that these compounds could have many conformers that populate the low-energy minima on the potential energy surface (PES). The conformational space occupied by the ligands is large and, in vacuum, the rotation barriers of different flexible bonds have energies between 0.5 and thousands of kcal/mol. By optimization, most conformers have energy barriers of 0,5 kcal/mol; thus, they could interconvert easily to obtain better interactions in the receptor active site. Optimized conformers having energy barriers of >5 kcal/mol display bad geometries with very large bond lengths and deformed rings. Shapes and heights of rotation barriers obtained through COSMO,AM1 single-point calculations in water are similar to those obtained from single-point calculations in vacuum. However, in water the energy barriers are lower, allowing most conformers to convert in other low-energy conformers. The best conformers in vacuum and in water are different: the gas phase best conformer has a helical shape, while the best conformer in water has an extended shape. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source]

    Relative energies of conformations and sulfinyl oxygen-induced pentacoordination at silicon in 4-bromo- and 4,4-dibromo-4-silathiacyclohexane 1-oxide: A computational study

    Fillmore Freeman
    Abstract The equilibrium geometries and relative energies of the chair, twist, and boat conformations of cis - and trans -4-bromo-4-silathiacyclohexane 1-oxide and 4,4-dibromo-4-silathiacyclohexane 1-oxide have been calculated at the B3LYP/6-311G(d,p) and MP2/6-311+G(d,p) theoretical levels. The axial (SO) chair conformers of the sulfoxides are of lower energy than the chair conformers of the corresponding equatorial (SO) sulfoxides. The chair conformer of the axial (SO) trans -4-bromo-4-silathiacyclohexane 1-oxide is only 0.10 kcal/mol more stable than the corresponding 1,4-boat conformer which is stabilized by a transannular coordination of the sulfinyl oxygen with silicon that results in trigonal bipyramidal geometry at silicon. The 1,4-boat structure of equatorial (SO) trans -4-bromo-4-silathiacyclohexane 1-oxide is a transition state and is 5.77 kcal/mol higher in energy than the respective chair conformer. The 1,4-boat conformer of axial (SO) 4,4-dibromo-4-silathiacyclohexane 1-oxide is also stabilized by transannular coordination of the sulfinyl oxygen and silicon, but it is 4.31 kcal/mol higher in energy than the corresponding chair conformer. The relatively lower stability of the 1,4-boat conformer of 4,4-dibromo-4-silathiacyclohexane 1-oxide may be due to repulsive interactions of the axial halogen and sulfinyl oxygen atom. The relative energies of the conformers and transition states are discussed in terms of hyperconjugative interactions, orbital interactions, nonbonded interactions, and transannular sulfinyl oxygen-silicon coordination. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 [source]

    Intramolecular proton transfer induced by divalent alkali earth metal cation in the gas state

    Hongqi Ai
    Abstract Interactions between divalent alkali earth metal (DAEM) ions M (MBe, Mg, Ca, Sr, Ba) and the second stable glycine conformer in the gas phase, which can transfer into the ground-state glycine-M2+ (except the glycine,Be2+) among each corresponding isomers when these divalent metal ions are bound, are studied at the hybrid three-parameter B3LYP level with three different basis sets. Proton transfers from the hydroxyl to the amino nitrogen of the glycine without energy barriers have been first observed in the gas phase in these glycine,M2+ systems. The interaction between the glycine and these DAEM ions except beryllium and magnesium ion only create an amino hydrogen pointing to the original hydroxyl due to their weaker interaction relative to those divalent transition metal (DTM) ion-bound glycine derivatives, being obviously different from that between the glycine and DTM ions, in which two amino hydrogens point to the original hydroxyl oxygen when these metal-chelated glycine derivatives are produced. The interaction energy between the glycine and divalent magnesium would be the boundary of one or two amino hydrogens pointing to the hydrogyl oxygen, i.e., the ,170.3 kcal/mol of binding energy is a critical point. Similar intramolecular proton transfer has also been predicted for those DTM ion-chelated glycine systems; however, that in the gas state has not been observed in the monovalent metal ion-coordinated glycine systems. The binding energy between some monovalent TM ion and the glycine is similar to that of the glycine,Ba2+, which has the lowest binding strength among these DAEM,ion chelated glycine complexes. The difference among them only lies in the larger electrostatic and polarized effects in the latter, which favor the stability of the zwitterionic glycine form in the gas phase. According to these observations, we predict that the zwitterionic glycine would exist in the field of two positive charges in the gas phase. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 205,214, 2003 [source]

    27 ps DFT molecular dynamics simulation of ,-maltose: A reduced basis set study,

    Udo Schnupf
    Abstract DFT molecular dynamics simulations are time intensive when carried out on carbohydrates such as ,-maltose. In a recent publication (Momany et al., J. Mol. Struct. THEOCHEM, submitted) forces for dynamics were generated from B3LYP/6-31+G* electronic structure calculations. The implicit solvent method COSMO was applied to simulate the solution environment. Here we present a modification of the DFT method that keeps the critical aspects of the larger basis set (B3LYP/6-31+G*) while allowing the less-essential atom interactions to be calculated using a smaller basis set, thus allowing for faster completion without sacrificing the interactions dictating the hydrogen bonding networks in ,-maltose. In previous studies, the gg,-gg-c solvated form quickly converged to the "r" form during a 5 ps dynamics run. This important conformational transition is tested by carrying out a long 27 ps simulation. The trend for the "r" conformer to be most stable during dynamics when fully solvated, is confirmed, resulting in ,20/80% c/r population. Further, the study shows that considerable molecular end effects are important, the reducing end being fairly stable, the O6H pointing at the O5, while the nonreducing end moves freely to take on different conformations. Some "kink" and transition state forms are populated during the simulation. The average H1,···H4 distance of 2.28 Å confirms that the syn form is the primary glycosidic conformation, while the average C1,O1,C4 bond angle was 118.8°, in excellent agreement with experimental values. The length of this simulation allowed the evaluation of vibrational frequencies by Fourier transform of the velocity correlation function, taken from different time segments along the simulation path. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 [source]

    Electronic structure and reactivity of guanylthiourea: A quantum chemical study

    Ahmed Mehdi
    Abstract Electronic structure analysis of guanylthiourea (GTU) and its isomers has been carried out using quantum chemical methods. Two major tautomeric classes (thione and thiol) have been identified on the potential energy (PE) surface. In both the cases conjugation of pi-electrons and intramolecular H-bonds have been found to play a stabilizing role. Various isomers of GTU on its PE surface have been analyzed in two different groups (thione and thiol). The interconversion from the most stable thione conformer (GTU-1) to the most stable thiol conformer (GTU-t1) was found to take place via bimolecular process which involves protonation at sulfur atom of GTU-1 followed by subsequent CN bond rotation and deprotonation. The detailed analysis of the protonation has been carried out in gas phase and aqueous phase (using CPMC model). Sulfur atom (S1) was found to be the preferred protonation site (over N4) in GTU-1 in gas phase whereas N4 was found to be the preferred site of protonation in aqueous medium. The mechanism of S-alkylation reaction in GTU has also been studied. The formation of alkylated analogs of thiol isomers (alkylated guanylthiourea) is believed to take place via bimolecular process which involves alkyl cation attack at S atom followed by CN bond rotation and deprotonation. The reactive intermediate RS(NH2)CNC(NH2)2+ belongs to the newly identified ,N(,L)2 class of species and provides the necessary dynamism for easy conversion of thione to thiol. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010 [source]

    Molecular dynamics simulations of fluid methane properties using ab initio intermolecular interaction potentials

    Shih-Wei Chao
    Abstract Intermolecular interaction energy data for the methane dimer have been calculated at a spectroscopic accuracy and employed to construct an ab initio potential energy surface (PES) for molecular dynamics (MD) simulations of fluid methane properties. The full potential curves of the methane dimer at 12 symmetric conformations were calculated by the supermolecule counterpoise-corrected second-order Møller-Plesset (MP2) perturbation theory. Single-point coupled cluster with single and double and perturbative triple excitations [CCSD(T)] calculations were also carried out to calibrate the MP2 potentials. We employed Pople's medium size basis sets [up to 6-311++G(3df, 3pd)] and Dunning's correlation consistent basis sets (cc-pVXZ and aug-cc-pVXZ, X = D, T, Q). For each conformer, the intermolecular carbon,carbon separation was sampled in a step 0.1 Å for a range of 3,9 Å, resulting in a total of 732 configuration points calculated. The MP2 binding curves display significant anisotropy with respect to the relative orientations of the dimer. The potential curves at the complete basis set (CBS) limit were estimated using well-established analytical extrapolation schemes. A 4-site potential model with sites located at the hydrogen atoms was used to fit the ab initio potential data. This model stems from a hydrogen,hydrogen repulsion mechanism to explain the stability of the dimer structure. MD simulations using the ab initio PES show quantitative agreements on both the atom-wise radial distribution functions and the self-diffusion coefficients over a wide range of experimental conditions. © 2008 Wiley Periodicals, Inc. J Comput Chem 2009 [source]

    First-principle studies of intermolecular and intramolecular catalysis of protonated cocaine

    Chang-Guo Zhan
    Abstract We have performed a series of first-principles electronic structure calculations to examine the reaction pathways and the corresponding free energy barriers for the ester hydrolysis of protonated cocaine in its chair and boat conformations. The calculated free energy barriers for the benzoyl ester hydrolysis of protonated chair cocaine are close to the corresponding barriers calculated for the benzoyl ester hydrolysis of neutral cocaine. However, the free energy barrier calculated for the methyl ester hydrolysis of protonated cocaine in its chair conformation is significantly lower than for the methyl ester hydrolysis of neutral cocaine and for the dominant pathway of the benzoyl ester hydrolysis of protonated cocaine. The significant decrease of the free energy barrier, ,4 kcal/mol, is attributed to the intramolecular acid catalysis of the methyl ester hydrolysis of protonated cocaine, because the transition state structure is stabilized by the strong hydrogen bond between the carbonyl oxygen of the methyl ester moiety and the protonated tropane N. The relative magnitudes of the free energy barriers calculated for different pathways of the ester hydrolysis of protonated chair cocaine are consistent with the experimental kinetic data for cocaine hydrolysis under physiologic conditions. Similar intramolecular acid catalysis also occurs for the benzoyl ester hydrolysis of (protonated) boat cocaine in the physiologic condition, although the contribution of the intramolecular hydrogen bonding to transition state stabilization is negligible. Nonetheless, the predictability of the intramolecular hydrogen bonding could be useful in generating antibody-based catalysts that recruit cocaine to the boat conformation and an analog that elicited antibodies to approximate the protonated tropane N and the benzoyl O more closely than the natural boat conformer might increase the contribution from hydrogen bonding. Such a stable analog of the transition state for intramolecular catalysis of cocaine benzoyl-ester hydrolysis was synthesized and used to successfully elicit a number of anticocaine catalytic antibodies. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 980,986, 2005 [source]

    Solvent effects on glycine II.

    Water-assisted tautomerization
    Abstract The water-assisted tautomerization of glycine has been investigated at the B3LYP/6-31+G** level using supermolecules containing up to six water molecules as well as considering a 1:1 glycine,water complex embedded in a continuum. The conformations of the tautomers in this mechanism do not display an intramolecular H bond, instead the functional groups are bridged by a water molecule. The replacement of the intramolecular H bond by the bridging water reduces the polarity of the NH bond in the zwitterion and increases that of the OH bond in the neutral, stabilizing the zwitterion. Both the charge transfer effects and electrostatic interactions stabilize the nonintramolecularly H-bonded zwitterion conformer over the intramolecularly hydrogen bonded one. The nonintramolecularly H-bonded neutral is favored only by charge transfer effects. Although there is no strong evidence whether the intramolecularly hydrogen bonded or non hydrogen bonded structures are favored in the bulk solution represented as a dielectric continuum, it is likely that the latter species are more stable. The free energy of activation of the water-assisted mechanism is higher than the intramolecular proton transfer channel. However, when the presumably higher conformational energy of the zwitterion reacting in the intramolecular mechanism is taken into account, both mechanisms are observed to compete. The various conformers of the neutral glycine may form via multiple proton transfer reactions through several water molecules instead of a conformational rearrangement. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 690,703, 2004 [source]

    A computational study of conformational interconversions in 1,4-dithiacyclohexane (1,4-dithiane)

    Fillmore Freeman
    Abstract Ab initio molecular orbital theory with the 6-31G(d), 6-31G(d,p), 6-31+G(d), 6-31+G(d,p), 6-31+G(2d,p), 6-311G(d), 6-311G(d,p), and 6-311+G(2d,p) basis sets and density functional theory (BLYP, B3LYP, B3P86, B3PW91) have been used to locate transition states involved in the conformational interconversions of 1,4-dithiacyclohexane (1,4-dithiane) and to calculate the geometry optimized structures, relative energies, enthalpies, entropies, and free energies of the chair and twist conformers. In the chair and 1,4-twist conformers the CHax and CHeq bond lengths are equal at each carbon, which suggest an absence of stereoelectronic hyperconjugative interactions involving carbon,hydrogen bonds. The 1,4-boat transition state structure was 9.53 to 10.5 kcal/mol higher in energy than the chair conformer and 4.75 to 5.82 kcal/mol higher in energy than the 1,4-twist conformer. Intrinsic reaction coordinate (IRC) calculations showed that the 1,4-boat transition state structure was the energy maximum in the interconversion of the enantiomers of the 1,4-twist conformer. The energy difference between the chair conformer and the 1,4-twist conformer was 4.85 kcal/mol and the chair-1,4-twist free energy difference (,G°c-t) was 4.93 kcal/mol at 298.15 K. Intrinsic reaction coordinate (IRC) calculations connected the transition state between the chair conformer and the 1,4-twist conformer. This transition state is 11.7 kcal/mol higher in energy than the chair conformer. The effects of basis sets on the 1,4-dithiane calculations and the relative energies of saturated and unsaturated six-membered dithianes and dioxanes are also discussed. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 909,919, 2003 [source]

    Quantum mechanical study of the conformational behavior of proline and 4R-hydroxyproline dipeptide analogues in vacuum and in aqueous solution

    Caterina Benzi
    The conformational behavior of the title compounds has been investigated by Hartree,Fock, MP2, and DFT computations on the most significant structures related to variations of the backbone dihedral angles, cis/trans isomerism around the peptide bond, and diastereoisomeric puckering of the pyrrolidine ring. In vacuum the reversed , turn (,l), characterized by an intramolecular hydrogen bridge, corresponds to the absolute energy minimum for both puckerings (up and down) of the pyrrolidine ring. An additional energy minimum is found in the helix region, but only for an up puckering of the pyrrolidine ring. When solvent effects are included by means of the polarizable continuum model the conformer observed experimentally in condensed phases becomes the absolute minimum. The down puckering is always favored over its up counterpart, albeit by different amounts (0.4,0.5 kcal/mol for helical structures and about 2 kcal/mol for ,l structures). In helical structures cis arrangements of the peptide bond are only slightly less stable than their trans counterparts. This is no longer true for ,l structures, because the formation of an intramolecular hydrogen bond is possible only for trans peptide bonds. In most cases, proline and hydroxyproline show the same general trends; however, the electronegative 4(R) substituent of hydroxyproline leads to a strong preference for up puckerings irrespective of the backbone conformation. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 341,350, 2002 [source]

    Intramolecular interactions and intramolecular hydrogen bonding in conformers of gaseous glycine

    L. F. Pacios
    Abstract Ab initio calculations at the MP2/6-311++G** level of theory led recently to the identification of 13 stable conformers of gaseous glycine with relative energies within 11 kcal/mol. The stability of every structure depends on subtle intramolecular effects arising from conformational changes. These intramolecular interactions are examined with the tools provided by the Atoms In Molecules (AIM) theory, which allows obtaining a wealth of quantum mechanics information from the molecular electron density ,(r). The analysis of the topological features of ,(r) on one side and the atomic properties integrated in the basins defined by the gradient vector field of the density on the other side makes possible to explore the different intramolecular effects in every conformer. The existence of intramolecular hydrogen bonds on some conformers is demonstrated, while the presence of other stabilizing interactions arising from favorable conformations is shown to explain the stability of other structures in the potential energy surface of glycine. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 702,716, 2001 [source]

    Structural characterization of cyclic kallidin analogues in DMSO by nuclear magnetic resonance and molecular dynamics

    Elisabetta Schievano
    Abstract The conformational properties in DMSO of two head-to-tail cyclic analogues of kallidin ([Lys0]-bradykinin, KL) as well as those of the corresponding linear peptides were studied by NMR and molecular dynamics (MD) simulations. The modifications in the sequence were introduced at position 6, resulting in the four peptides, [Tyr6]-KL (YKL), [Trp6]-KL (WKL), cyclo-([Tyr6]-KL) (YCKL) and cyclo-([Trp6]-KL) (WCKL). The linear WKL analogue was significantly more potent than kallidin on rat duodenum preparations, whereas YKL was significantly less potent. Both cyclic peptides, YCKL and WCKL displayed similar activity, lower than that of the linear analogues and also of cyclo-KL. The two linear analogues display high conformational flexibility in DMSO. In the predominant conformer, for both peptides, all three X-Pro bonds adopt a trans configuration. Three out of four conformers present in YCKL and WCKL were completely assigned. The configurations at the X-Pro bonds are the same for the two analogues. All cyclic conformers show a cis configuration in at least one X-Pro bond and always opposite configuration for the two consecutive X-Pro bonds. The NOE-restrained MD calculations resulted in the detection of several elements of secondary structure in each of the conformers. Such elements are described and their possible relevance to biological activity is discussed. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source]

    Effect of metal cations on the conformation and inactivation of recombinant human factor VIII

    Tiffany S. Derrick
    Abstract Heavy metals have been implicated in the aggregation of proteins and the pathophysiology of several neurodegenerative diseases. Herein, we describe the interaction of recombinant human factor VIII (rhFVIII) with Al+3, Tb+3, Co+2, and Fe+3 using a combination of intrinsic fluorescence, circular dichroism, and high-resolution fourth-derivative absorbance analysis. rhFVIII in solution was titrated with the metal cations and the properties of the resulting complexes were examined. rhFVIII has a tendency to aggregate and inactivate slowly over time under physiological conditions, but this aggregation process is greatly accelerated in the presence of metals with Al+3 being the most efficient. This leads to a complete loss of activity of the protein. Al+3 -induced conformational changes in the protein were small but detectable with limited changes seen in secondary and tertiary structure. Because rhFVIII is a multidomain protein with subunits linked through divalent metal cations, the small intramolecular changes seen may be attributed to rearrangements of the subunits to an aggregation-competent conformer that is very similar to that of the native form. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2549,2557, 2004 [source]

    Poly(L-lysine) as a model drug macromolecule with which to investigate secondary structure and membrane transport, part I: physicochemical and stability studies

    Montakarn Chittchang
    Low oral bioavailability of therapeutic peptides and proteins generally results from their poor permeability through biological membranes and enzymatic degradation in the gastrointestinal tract. Since different secondary structures exhibit different physicochemical properties such as hydrophobicity, size and shape, changing the secondary structure of a therapeutic polypeptide may be another approach to increasing its membrane permeation. Poly(L-lysine) was used as a model polypeptide. The objectives of this study were to induce secondary structural changes in poly(L-lysine) and to determine the time course over which a given conformer was retained. In addition, the hydrophobicity of each secondary structure of poly(L-lysine) was assessed. The circular dichroism (CD) studies demonstrated that the conditions employed could successfully induce the desired secondary structural changes in poly(L-lysine). The ,-helix conformer appeared to be more stable at 25° C whereas the ,-sheet conformer could be preserved at 37° C. On the other hand, the random coil conformer was retained at both temperatures. Significant losses of the ,-helix and the ,-sheet conformers were observed when the pH was reduced. The change in ionic strength did not affect any of the conformers. The octanol/buffer partitioning studies indicated that the ,-helix and the ,-sheet conformers exhibited significantly different (P< 0.05) hydrophobicities. In conclusion, variation of pH and temperature conditions can be used to induce secondary structural changes in poly(L-lysine). These changes are reversible when the stimuli are removed. The ,-helix and the ,-sheet conformers of poly(L-lysine) are more lipophilic than the native random coil conformer. Thus, poly(L-lysine) may represent an ideal model polypeptide with which to further investigate the effects of secondary structure on membrane diffusion or permeation. [source]

    Structural and vibrational study of 2-(2,- furyl)-4,5-1H -dihydroimidazole

    Juan Zinczuk
    Abstract In this study 2-(2,-furyl)-4,5-1H -dihydroimidazole (1) was prepared and then characterized by infrared, Raman, and multidimensional nuclear magnetic resonance (NMR) spectroscopies. The crystal and molecular structures of 1 were determined by X-ray diffraction methods. The density functional theory (DFT) and second-order Møller,Plesset theory (MP2) with Pople's basis set show that there are two conformers for the title molecule that have been theoretically determined in the gas phase, and that only one of them, conformer I, is present in the solid phase. NMR spectra observed for 1 were successfully compared with the calculated chemical shifts at the B3LYP/6-311++G** level theorized for this conformer. The harmonic vibrational frequencies for the optimized geometry of the latter conformer were calculated at the B3LYP/6-311++G** level in the approximation of the isolated molecule. For a complete assignment of the IR and Raman spectra in the solid phase of 1, DFT calculations were combined with Pulay´s scaled quantum mechanics force field (SQMFF) methodology to fit the theoretical frequency values to the experimental ones. Copyright © 2009 John Wiley & Sons, Ltd. [source]

    Comparative DFT study on the role of conformers in the ruthenium alkylidene-catalyzed ROMP of norborn-2-ene

    Sergej Naumov
    Abstract Comparative quantum chemical calculations on the reaction pathways for the formation of ruthena(IV)cyclobutanes from both 1st - and 2nd -generation Grubbs catalysts of the general formula RuX2(L)(L,)(CH2) (L,=,PCy3 or 1,3-dimesityl-4,5-dihydroimidazolin-2-ylidene, L,,=,PCy3) and norborn-2-ene (NBE) were carried out on the B3LYP/LACVP** level in dependence on the ligand X,=,I, Br, Cl, and F. The mechanism proposed by Straub for the formation of (one) active and (three) inactive NBE,Ru,carbene complexes for non-cyclic alkenes was applied to the cyclic alkene NBE. In RuX2(PCy3)2(CH2), the inactive NBE,Ru,carbene complex is energetically more stable than the active one; however, in RuX2(IMesH2)(PCy3)(CH2), the active NBE,Ru,carbene complex is more stable than the inactive one. In due consequence, the possible rate limiting barrier for the conversion of the NBE,Ru,carbene complex into the corresponding metallocyclobutane (MCB) is systematically larger in the case of 1st -generation Grubbs catalysts than of 2nd -generation Grubbs catalysts due to an additional re-arrangement for the formation of an active , -complex from the more stable (inactive) conformer. This correlates with the observed reactivity of both types of initiators. There is a strong influence of the ligands L and X on the conformational properties and relative stabilities of the 14-electron intermediates, which has a direct effect on the distribution of the inactive and active conformations of the corresponding Ru,carbene,NBE complexes. A direct correlation between the conformational properties of the 14-electron intermediates and the relative stabilities of the active Ru,carbene,NBE complexes was observed. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    Anomeric effect plays a major role in the conformational isomerism of fluorinated pnictogen compounds

    Levindo E. Martins
    Abstract According to our theoretical studies, the anomeric effect, an stereoelectronic interaction between lone pair and a vicinal antibonding orbital, has shown to contribute decisively for the conformational isomerism of 1-fluoro- N,N -dimethylmethanamine (1) and of its corresponding P, As and Sb analogues (2,4). CX bonds in 2,4 are larger than in the parent compound 1, thus providing a LPX/CF* interaction progressively weaker on going from 1 to 4. However, such hyperconjugation contributed by more than 1.3,kcal,mol,1 for the stabilization of anti conformer in 4 (,LPXCF,=,180°), increasing to 24.1,kcal,mol,1 in 1. An isodesmic reaction model supported these findings. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    Conformational analysis, Part 41.

    -unsaturated carbonyl compounds, A modelling, LIS/NMR investigation of the conformations of
    Abstract A novel Lanthanide Induced Shift Analysis (LISA) is presented. In this analysis both the paramagnetic and the diamagnetic lanthanide induced chemical shifts are normalised separately in contrast to previous techniques in which only the paramagnetic shifts were normalised. This procedure is used together with molecular mechanics (MMFF94) and ab initio (RHF/6-31G, RHF/6-311G** and B3LYP/6-311G**) calculations to investigate s - cis/s - trans isomerism in some ,,, -unsaturated aldehydes, ketones and esters. In tiglic aldehyde 1 and trans -cinnamaldehyde 4 the s - trans conformer predominates with energy differences ,E (s - cis,s - trans) of 1.64 and 1.76,kcal/mol. In methyl vinyl ketone 2 and trans -cinnamyl methyl ketone 5 the populations of the s - cis and s - trans isomers are almost equal (,E 0.24 and 0.0,kcal/mol) and in methyl crotonate 3 and methyl trans -cinnamate 6 the s - cis conformer is more stable (,E ,0.72 and ,0.41,kcal/mol). These results are in agreement with both the MMFF94 and ab initio calculated energies for the compounds except tiglic aldehyde 1 in which all the calculated values are too large and cinnamyl ketone 5. In this compound the ab initio calculations predict the s - cis form to be more stable than the s - trans in contrast to both the MM calculations and the observed result which give both forms of equal energy. Also in both the MM and ab initio calculations phenyl substitution in the ketone (2 vs. 5) considerably stabilises the s - cis form. This is not observed in practise. In phenyl acetate 7 the B3LYP calculations give two equally stable structures, one planar one non-planar. The MMFF94 and MP2 calculations and the LIS analysis support the existence of only the non -planar conformer in solution, which is also the conformation of phenyl acetate in the crystal. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    Computational study of the chair,chair interconversion and stereoelectronic interactions in 1,2,3-trithiacyclo-hexane (1,2,3-trithiane)

    Fillmore Freeman
    Abstract Ab initio theory, density functional theory (DFT) and Møller,Plesset perturbation theory (MP2) with the 6,31G(d), 6,31++G(d), 6,31G(d,p), 6,31+G(d,p), 6,31++G(d,p), 6,311G(d,p) and 6,311+G(d,p) basis sets were used to study stereoelectronic hyperconjugative interactions and the mechanism of the chair,chair conformational interconversion in 1,2,3-trithiacyclohexane (1,2,3-trithiane). The relative energies, enthalpies, entropies, free energies and structural parameters of the chair, 1,4-twist and 2,5-twist conformers, a distorted 1,4-boat transition state and a 2,5-boat transition state were calculated. The HF calculated energy difference (,E) between the chair conformer of 1,2,3-trithiane and the distorted 1,4-boat transition state was 10.59,kcal,mol,1 (1 kcal=4.184,kJ). The 1,4-twist conformer and the 2,5-boat transition state are close in energy, as are the 2,5-twist conformer and the distorted 1,4-boat transition state. B3LYP/6,311+G(d,p) calculated the chair conformer of 1,2,3-trithiane to be 5.83, 10.09, and 5.96,kcal,mol,1, respectively, lower in energy than the 1,4-twist conformer, 2,5-twist conformer and 2,5-boat transition state. Intrinsic reaction coordinate (IRC) calculations were used to connect the transition state between the chair conformer and the 1,4-twist conformer. B3LYP/6,31+G(d,p) and B3LYP/6,311+G(d,p) calculated this transition state to be 14.25,kcal,mol,1 higher in energy than the chair conformer. In the chair conformer, the respective C4,H and C6,H bond lengths are equal, but the C5,Heq bond is longer than the C5,Hax bond. In the 1,4-twist conformer, the C4,Hiso bond lengths are equal, the C5,H,eq bond is longer than the C5,H,ax bond and the C6,H bond lengths are equal. In the 2,5-twist conformer, equal C,H bond lengths are found at C4 and at C5, but the C6,H,eq bond is longer than the C6,H,ax bond. Copyright © 2003 John Wiley & Sons, Ltd. Additional material for this paper is available in Wiley Intersciene [source]

    NMR, solvation and theoretical investigations of conformational isomerism in 2-X-cyclohexanones (X=NMe2, OMe, SMe and SeMe)

    Matheus P. Freitas
    Abstract The conformational equilibria of 2- N,N -dimethylamino- (1), 2-methoxy- (2), 2-methylthio- (3) and 2-methylselenocyclohexanone (4) were determined in various solvents by measurement of the 3JH-2,H-3 couplings. The observed couplings were analyzed using theoretical and solvation calculations to give both the conformer energies in the solvents studied plus the vapor-phase energies and the coupling constants for the distinct conformers. These gave the conformer energies and couplings of 2,4. The intrinsic couplings for the 2- N,N -dimethylamino compound were determined by the molecular mechanics PCMODEL program. The axial conformation in 1 is the most polar and also more stable in DMSO solution (Eeq,Eax=0.05,kcal,mol,1) and the pure liquid, while the equatorial conformer predominates in the remaining solvents studied (except in CCl4, where self-association is observed). In the methoxy ketone (2) the equatorial conformation is more stable in the vapor (Eeq,Eax=,0.30,kcal,mol,1) and in all solvents. The opposite behavior is shown by 3 and 4, where the axial conformation is the more stable one in the vapor phase (Eeq,Eax=1.60 and 2.95,kcal,mol,1 for 3 and 4, respectively) and is still the prevailing conformer in solution. The axial predominance for 3 and 4 is attributed to hyperconjugation between the electron lone pair of the hetero-substituent and the ,*CO orbital. This interaction is stronger for 3 and 4 than in the case of 1 and 2, where the ,gauche effect' in the equatorial conformation should be more effective in stabilizing this conformation. Copyright © 2003 John Wiley & Sons, Ltd. [source]

    Raman and infrared spectra, conformational stability, ab initio calculations and vibrational assignment of dimethylsilylisocyanate

    Gamil A. Guirgis
    Abstract The Raman (3200-30 cm,1) and/or infrared spectra (3500 to 400 cm,1) of gaseous, liquid and solid dimethylsilylisocyanate, (CH3)2 Si(H)NCO, have been recorded. The MP2(full) calculations, employing a variety of basis sets with and without diffusion functions, have been used to predict the structural parameters, conformational stability, vibrational fundamental wavenumbers, Raman activities, depolarization values and infrared intensities to support the vibrational assignment. The low wavenumber Raman spectrum of the gas with a significant number of Q-branches for the SiNC(O) bend is consistent with an essentially linear SiNCO moiety. The ab initio calculations supported this conclusion as all possible orientations of the NCO moiety lead to nearly the same energy. This result is at variance with the conclusion from the electron diffraction study that the heavy atom skeleton was bent with an angle of 152(5)° with one stable cis conformer. It is believed that this reported angle difference from 180° is due to the shrinkage effect. The SiH distance of 1.486 Å has been obtained from the isolated SiH stretching wavenumber. From the adjustment of the ab initio MP2(full)/6-311+G(d,p) predicted structural parameters, a proposed structure is reported, which is expected to give rotational constants within a few megahertz of the actual ones. These experimental and theoretical results are compared with the corresponding quantities of similar molecules. Copyright © 2009 John Wiley & Sons, Ltd. [source]