Probing the electronic structure of peptide bonds using methyl groups

The observed V3 torsional barriers measured by microwave spectroscopy for nine methyl groups attached alpha to peptide bond linkages in five gas-phase biomimetics have been found to differ considerably from one molecule to the next and even depend on the position of substitution, being sensitive to structural changes at the other end of the peptide bond. In the search for an explanation for these results, ab initio calculations have been performed at the HF/6-311++G(d,p) level of theory and interpreted in terms of the natural bond orbitals and resonance structures of the peptide bond. These calculations reveal that resonance delocalization in peptide bonds is influenced by methyl conformation through the coupling of vicinal sigma to sigma* orbital interactions with the n to pi*. Thus, CN double-bond character increases (and CO double-bond character decreases) as the methyl group is rotated from the syn to the anti position. A quasilinear correlation exists between the barriers to internal rotation of attached methyl groups and the relative importance of the two principal resonance structures that contribute to the peptide bond.     

Controlled synthesis of a structurally characterized family of sterically constrained heterocyclic alkoxy-modified titanium alkoxides

The reaction of [Ti(mu-ONep)(ONep)3]2 (ONep = OCH2C(CH3)3) with a series of heterocyclic methanol derivatives [tetrahydrofurfuryl alcohol (H-OTHF), thiophene methanol (H-OTPM), or 2-pyridylcarbinol (H-OPy)-collectively termed H-OR*], led to the isolation of a novel family of OR*-substituted titanium alkoxide precursors. Independent of the initial stoichiometry for the H-OTHF reaction, a monosubstituted, dinuclear species was isolated as [(ONep)3Ti(muc-OTHF)]2 (1). For 1, each Ti was octahedrally (Oh) bound by three terminal ONep ligands, one bidentate bridging OTHF ligand (muc-OTHF), and an oxygen from the other muc-OTHF ligand. For the OTPM derivatives, the product was identified as [(ONep)3Ti(mu-OTPM)]2 (2). For this ligand, the soft S atom does not bind to the Ti but the O atom does act as a bridge between the two trigonal bipyramidal bound Ti metal centers. The OPy system yielded (OPy)2Ti(OR)2 independent of the OR and the stoichiometry used [OR = ONep (3), OCHMe2 (4), OCMe3 (5)]. For 3-5, the two OPy ligands chelate to the Oh-bound Ti metal center with two terminal OR ligands. Compounds 1-5 were fully characterized using a variety of analytical techniques. An initial investigation of the proposed chemical stability of the '(OPy)2Ti' moiety of 3-5 to alcoholysis exchange pathways involving (i) alkyl alcohols, (ii) aryl alcohols, (iii) substituted phenols, (iv) H-OR* derivatives, and (v) silanols proved successful through the isolation of a novel family of structurally characterized (OPy)2Ti(OR')2 (7-24) compounds.     

Secondary decomposition of C3H5 radicals formed by the photodissociation of 2-bromopropene

The photodissociation of 2-bromopropene at 193 nm produces C(3)H(5) radicals with a distribution of internal energies that spans the threshold for the secondary decomposition of the 2-propenyl radicals into C(3)H(4)+H. Just above this threshold, the decomposition rate is on the nanosecond time scale, and in the present study, time-resolved velocity-map ion imaging is used to gain insight into this process. The results provide information on the energy dependence of the secondary dissociation process. In addition, comparison of the results with theoretical predictions of the energy dependence of the dissociation rate provides information on the branching between fragment rotational and vibrational energies in the primary photodissociation process.     

Contrasting nonaqueous against aqueous solvation on the basis of scaled-particle theory

Normal hexane is adopted as a typical organic solvent for comparison with liquid water in modern theories of hydrophobic hydration, and detailed results are worked-out here for the C-atom density in contact with a hard-sphere solute, rhoCG(R), for the full range of solute radii. The intramolecular structure of an n-hexane molecule introduces qualitative changes in G(R) compared to scaled-particle models for liquid water. Also worked-out is a revised scaled-particle model implemented with molecular simulation results for liquid n-hexane. The classic scaled-particle model, acknowledging the intramolecular structure of an n-hexane molecule, is in qualitative agreement with the revised scaled-particle model results, and is consistent in sizing the methyl/methylene sites which compose n-hexane in the simulation model. The classic and revised scaled-particle models disagree for length scales greater than the radius of a methyl group, however. The liquid-vapor surface tension of n-hexane predicted by the classic scaled-particle model is too large, though the temperature variation is reasonable; this contrasts with the classic scaled-particle theory for water which predicts a reasonable magnitude of the water liquid-vapor surface tension, but an incorrect sign for the temperature derivative at moderate temperatures. Judging on the basis of the arbitrary condition that drying is indicated when G(R)<1, hard spheres dry at smaller sizes in n-hexane than in liquid water.     

Isostructural or not? Adducts of some aryl­tin halides with (E)‐1,2‐bis(4‐pyridyl)­ethene

The title complexes [μ‐(E)‐4,4′‐(ethene‐1,2‐diyl)­di­pyridine‐κ²N:N′]­bis­[halotris(4‐methyl­phenyl)­tin(IV)], [Sn₂(C₇H₇)₆X₂(C₁₂H₁₀N₂)], where halo is chloro (X = Cl) and bromo (X = Br) are isostructural. In both crystals, the mol­ecules lie on inversion centers, and there are voids of ca 80 ų that could, but apparently do not, accommodate water mol­ecules. The corresponding iodo structure (X = I) is almost, but not quite, isostructural with the other two compounds; when Br is changed to I, the length of the c axis decreases by more than 1 Å and the voids are no longer large enough to accomodate any solvent mol­ecule. The related complex [μ‐(E)‐4,4′‐(ethene‐1,2‐diyl)­di­pyridine‐κ²N:N′]­bis­[chloro­tri­phenyl­tin(IV)], [Sn₂(C₆H₅)₆Cl₂(C₁₂H₁₀N₂)], crystallizes in a related structure, but the mol­ecules lie on general rather than on special positions. The molecular structures of the four complexes are similar, but the conformation of the phenyl derivative is approximately eclipsed rather than staggered.     

Structure conditioned velocity statistics in a high pressure swirl flame

A piloted, partially premixed, liquid-fueled swirl burner is operated at high pressure (1 MPa). High-speed (6 KHz) stereoscopic PIV is used to investigate the characteristics of the stagnation line separating the pilot jet and the central recirculation zone (CRZ) with varying pilot-main ratio and global equivalence ratio. The mean curvature of the stagnation line displayed a large spatial scale pattern that was present for all operating conditions. All three components of velocity, in-plane shear, and swirling strength are conditioned upon the instantaneous stagnation line. Mean distributions of the velocity normal to the stagnation line show that velocity is oriented towards the CRZ when the stagnation line is found nearer the centerline of the combustor. The conditioned out-of-plane velocity (w) shows a distinct concentration of large mean and fluctuation RMS values towards the center of the measurement domain. Varying fuel flow does not significantly change this spatial structure, only the magnitudes of the w statistics. The in-plane shear stress was the largest for the pilot biased condition as a stronger shear layer develops. For the leanest flame, large fluctuation RMS values of shear stress were confined to a region where the pilot jet begins to interact more heavily with the main jet. Operating with less pilot fuel flow enhanced the mean conditional swirling strength indicating that the pilot shear layer was shedding more intense eddies. Disregarding spatial relations, a scatter plot of w, shear stress, and swirling strength displayed trends between the variables. The largest swirling strength values coincide with highest magnitude shear stresses and the widest range of w. These conditioned statistics highlight how certain aspects of the combustor flow field are invariant with fuel distribution. This is desirable for aeropropulsive combustors that must maintain stable ignition from a range of conditions from landing/take-off to cruise.     

Synthesis and evaluation of ketophosph(on)ates as beta-lactamase inhibitors

A series of amidoketophosph(on)ates of general structure PhCH2OCONHCH(R)COCHR'(CH2)n(O)P(O2-)(O)R' (R = H, CH3; R' = H, CH3; n = 0, 1; R' = H, CH3, Et, Ph) have been prepared as a potential source of beta-lactamase inhibitors. The phosphonates (n = 0) were obtained by means of the Arbuzov reaction while most of the phosphates were achieved from reaction of phosph(or/on)ic acids with the appropriate diazoketone PhCH2OCONHCH(R)COCR'N2. The electrophilicity of the carbonyl group in the resulting phosph(on)ates was assessed by the degree of hydration in aqueous solution, determined from NMR spectra. These compounds inhibited typical class C and class D beta-lactamases, particularly the latter group, but showed no activity against class A enzymes. To enhance the carbonyl electrophilicity, an alpha-difluorinated analogue (R = H, CHR' = CF2, n = 0, R' = Et) was also prepared, but no enhanced inhibitory activity was observed. All evidence suggested that these compounds inhibited in the carbonyl form rather than by formation of tetrahedral adducts at the beta-lactamase active site. They show promise as leads to specific class D beta-lactamase inhibitors.     

Role of fluctuations in a snug-fit mechanism of KcsA channel selectivity

The thermodynamic exclusion of Na+ relative to K+ in potassium channels is examined by calculating the distribution of binding energies for Na+ and K+ in a model of the selectivity filter of the KcsA potassium channel. These distributions are observed to take a surprisingly simple form: Gaussian with a slight positive skewness that is insignificant in the present context. Complications that might be anticipated from these distributions are not problematic here. Na+ occupies the filter with a mean binding energy substantially lower than that of K+. The difference is comparable to the difference in hydration free energies of Na+ and K+ in bulk aqueous solution. Thus, the average energies of binding to the filter do not discriminate Na+ from K+ when measured from a baseline of the difference in bulk hydration free energies. The strong binding of Na+ constricts the filter, consistent with a negative partial molar volume of Na+ in water in contrast with a positive partial molar volume of K+ in water. Discrimination in favor of K+)can be attributed to the scarcity of favorable binding configurations for Na+ compared to K+. That relative scarcity is quantified as enhanced binding energy fluctuations, which reflects both the energetically stronger binding of Na+ and the constriction of the filter induced by Na+ binding.