The energetic and structural effects of single amino acid substitutions upon capped alpha-helical peptides containing 17 amino acid residues. An ONIOM DFT/AM1 study

We evaluate the effect of the amino acid mutations of glycine, leucine, valine, phenylalanine, serine, and proline for the 10th alanine in the capped peptide, acetly(Ala)(17)NH(2), upon the energies of the alpha-helices and beta-strands using ONIOM DFT/AM1 molecular orbital calculations. The relative stabilities of the alpha-helix (to the beta-strand) derive from the differences between the effects upon not only the helix but the strand as well. Thus, Ala --> Pro significantly destabilizes both but destabilizes the alpha-helix more, while Ala --> Gly stabilizes both but stabilizes the beta-strand more. The theoretical results are discussed in the context of the known experimental reports. We suggest that the solvation of the unfolded state drives the helix/coil equilibrium in solution.     

Analytical properties of conformal invariant four point functions

On the basis of the known group theoretical structure of the conformal invariant four point functions in the case of identical scalar fields ?(x) of scale dimension d,

$\text{<0|?(x}{}_1\text{)?(x}{}_2\text{)?(x}{}_3\text{)?(x}{}_4\text{)|0〉 = [(x}{}_1\text{?x}{}_4\text{)}{}^2\text{(x}{}_2\text{?x}{}_3\text{)}{}^2\text{]}{}^{\mathrm{-d}}\text{g(A,B),}$

the analytical properties of g(A, B) as a function of the harmonic ratios A and B are investigated. By imposing the conditions of spectrality and locality, and using invariance under complex dilatations, it is shown that the function g(A, B) must be homomorphic in the whole complex A-plane and B-plane with exception of the values A=0 and A=∞, B arbitrary, and B=0 and B=∞, A arbitrary.     

H-bonding cooperativity and energetics of alpha-helix formation of five 17-amino acid peptides

Five peptides, each containing 17 amino acids, have been completely geometrically optimized in their alpha-helical and beta-strand forms using a mixed DFT/AM1 procedure. B3LYP/D95** was used for the entire helical structures, while AM1 was initially used to optimize the side chains, followed by reoptimization at the DFT level. The energetic and structural results show (1) that the helices are favored over the strands by 29.5 to 37.4 kcal/mol; (2) that alkyl groups on the amino acid side chains favor helix formation even in the absence of solvent; (3) that C-H...O hydrogen bonds contribute to the relative stability of the helices that contain amino acids (val, leu and ile) with beta-hydrogens in their alkyl side chains; (4) that formation of these helices entails approximately 6.6 kcal/mol of strain within the backbone per hydrogen bond; and (5) that H-bond cooperativity is essential for the alpha-helix to become more stable than a corresponding beta-strand. This last observation strongly suggests that pairwise potentials are inadequate for modeling of peptides and proteins.     

Absolute configuration, predominant conformations, and vibrational circular dichroism spectra of enantiomers of n-butyl tert-butyl sulfoxide

Alkylation of the alpha-carbanion of (R)-(-)-tert-butyl methyl sulfoxide (4) with n-propyl bromide afforded (+)-n-butyl tert-butyl sulfoxide (1) to which the absolute configuration (R) was ascribed. This assignment was confirmed by X-ray analysis of the complex 6 obtained from the enantiomerically pure sulfoxide (-)-1 and mercury chloride. Vibrational absorption and circular dichroism spectra of (+)-1 were measured in CDCl3 solution in the 2000-900 cm(-1) region and compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using the B3LYP/6-31G basis set for different conformers of (R)-1. This comparison indicated also that (+)-1 is of the (R)-configuration.     

Metal vs ligand reduction in complexes of dipyrido[3,2-a:2',3'-c]phenazine and related ligands with [(C5Me5)ClM]+ (M = Rh or Ir): evidence for potential rather than orbital control in the reductive cleavage of the metal-chloride bond

Complexes between the chlorometal(III) cations [(C5Me5)ClM]+, M = Rh or Ir, and the 1,10-phenanthroline-derived alpha-diimine (N--N) ligands dipyrido[3,2-a:2',3'-c]phenazine (dppz), 1,4,7,10-tetraazaphenanthrene (tap), or 1,10-phenanthroline-5,6-dione (pdo) were investigated by cyclic voltammetry, EPR, and UV-vis-NIR spectroelectrochemistry with respect to either ligand-based or metal-centered (and then chloride-dissociative) reduction. Two low-lying unoccupied molecular orbitals (MOs) are present in each of these three N wedge N ligands; however, their different energies and interface properties are responsible for different results. Metal-centered chloride-releasing reduction was observed for complexes of the DNA-intercalation ligands dppz and tap to yield compounds [(N--N)(C5Me5)M] in a two-electron step. The separation of alpha-diimine centered optical orbitals and phenazine-based redox orbitals is apparent from the EPR and UV-vis-NIR spectroelectrochemistry of [(dppz)(C5Me5)M](0/*-/2-). In contrast, the pdo complexes undergo a reversible one-electron reduction to yield o-semiquinone radical complexes [(pdo)(C5Me5)ClM]* before releasing the chloride after the second electron uptake. The fact that the dppz complexes undergo a Cl(-)-dissociative two-electron reduction despite the presence of a lowest lying pi* MO (b1(phz)) with very little overlap to the metal suggests that an unoccupied metal/chloride-based orbital is lower in energy. This assertion is confirmed both by the half-wave reduction potentials of the ligands (tap, -1.95 V; dppz, -1.60 V; pdo, -0.85 V) and by the typical reduction peak potentials of the complexes [(L)(C5Me5)ClM](PF6) (tap, -1.1 V; dppz, -1.3 V; pdo, -0.6 V; all values against Fc(+/0)).     

Crystal and molecular structures of 1-(2-ethyloxycarbonylo propan-2-ylamino)-3-(1-napthyloxy) propan-2-ol-hydrochloride (1) (C19H26NO4Cl) and 1-(2-isopropyloxycarbonylo-propan-2-ylamino)-3-(1-napthyloxy) propan-2-ol hydrochloride (2) (C20H28N04Cl)

The crystal structures of two new-adrenergic antagonists, derivatives of propranolol, are shown in this paper. The space groups and unit-cell parameters are: compound1 (C₁₉H₂₆NO₄Cl): triclinic, space groupP1,a=6.420(1),b=10.161(1),c=15.823(1) Å,=82.47(1),=84.16(1), =77.55(1)°; compound 2 (C₂₀H₂₈NO₄Cl): monoclinic, space groupP2₁/c,a=6.460(1),b=33.285(2),c=10.120(1) Å,=104.83(1)°. The structures were solved by direct methods and refined with full-matrix least-squares techniques toR indices of 0.055 and 0.048, respectively. The –CH(OH)-CH₂-NH-sections of the side chains show the conformation approximate togauche.     

Crystal and molecular structures of 1-(2-carboxypropan-2-ylamino)-3-(1-naphthyloxy) propan-2-ol (1) (C17H21NO4) and 1-(2-carbamoyl propan-2-ylamino)-3-(1-naphthyloxy) propan-2-ol (2) (C17H22N2O3)

The crystal structures of two new-adrenergic antagonists, derivatives of propranolol containing 2-methylalanine fragment are described in this paper. The space groups and unit-cell parameters are: compound1 (C₁₇H₂₁NO₄): monoclinic, space groupP2₁/n,a=5.787(1),b=18.703(4),c=23.526(5)Å,=96.49(2)°; compound2 (C₁₇H₂₂N₂O₃): triclinic, space groupP¯1,a=8.321(1),b=10.121(1),c=10.368(1)Å,=109.49(1)°,=90.49(1)°, =103.48(1)°. The structures were solved by direct methods and refined with full matrix least-squares techniques toR indices of 0.055 and 0.049, respectively. The molecules of compound1 exist in the crystal as dual ions. The molecules of compound2 are compact and their external chain is twisted in a characteristic way (similar to that found in peptides).     

The synthesis and X-ray structural studies of 2-cholesteryl-2-thio-1,3,2-oxathiaphospholane and 2-cholesteryl-2-thio-1,3,2-dithiaphospholane

Two thiophospholane derivatives of cholesterol: 2-cholesteryl-2-thio-1,3,2-oxathiaphospholane (1) and 2-cholesteryl-2-thio-1,3,2-dithiaphospholane (2) were synthesized as new reagents for introducing a cholesteryl moiety at the 5-end of oligonucleotidesvia the phosphorothioate or phosphorodithioate bond. Compounds1 and2 were subjected to structural studies by X-ray methods. Both compounds crystallized in the orthorhombic system, space group P2₁2₁2₁,1 witha=6.283(1) Å,b=12.067(1) Å,c=38.983(3) Å,2 witha=6.371(1) Å,b=11.971(1) Å andc=39.502(3) Å. The five-membered heterocyclic rings of both compounds attain a half-chair conformation in the solid state. In structures of1 and2 a disorder of some atoms is observed. The absolute configuration at the phosphorus atom in1 of the components of diastereoisomeric mixture has been established.     

Crystal and molecular structures of 1-(2-iso butylylcarbamoyl propan-2-ylamino) 3-(1-naphthyloxy)propan-2-ol hydrochloride (1) (C21H31N2O3Cl) and 1-(2-isobutyloxycarbonylo propan-2-ylamino) 3-(1-naphthyloxy)propan-2-ol hydrochloride (2) (C21H30NO4Cl)

This paper shows the crystal structures of two new-adrenergic antagonists, derivatives of propranolol, which were determined with three-dimensional x-ray diffraction data. The space groups and unit-cell parameters are: compound1 (C₂₁H₃₁N₂O₃Cl) monoclinic space groupP2₁/c,a=20.523(4),b=6.909(2),c=15.950(2) Å,=105.03(1)°; compound2 (C₂₁H₃₁NO₄Cl) monoclinic space groupP2₁/c,a=6.364(2),b=36.043(8),c=10.149(1) Å,=104.48(2)°. The structures were solved with direct methods, and refined with full-matrix least-squares techniques toR indices of 0.059 and 0.067, respectively. The-CH(OH)-CH₂-NH-sections of the side chains show the conformation approximate togauche.