A theoretical study on the origin of cooperativity in the formation of 3(10)- and alpha-helices.

By using a simple repeating unit method, we have conducted a theoretical study which delineates the preferences for beta-strand, 2(7)-ribbon, 3(10)-helix, and alpha-helix formation for a series of polyglycine models up to 14 amino acid residues (Ac-(Gly)(n), n = 0, 1, 2,., 14). Interactions among residues, which result in cooperativity, are clearly indicated by variations in calculated energies of the residues. Whereas no cooperativity is found in the formation of beta-strands and 2(7)-ribbons, there is a significant cooperativity in the formation of 3(10)- and alpha-helices, especially for the latter. In the case of alpha-helices, the 14th residue is more stable than the 3rd by about 3 kcal/mol. A good correlation between calculated residue energy and residue dipole moment was uncovered, indicating the importance of long-range electrostatic interactions to the cooperativity. The results of our calculations are compared with those of the AMBER and PM3 methods, and indicate that both methods, AMBER and PM3, need further development in the cooperative view of electrostatic interactions. The result should be of importance in providing insight into protein folding and formation of helical structures in a variety of polymeric compounds. This also suggests a strategy for the development of more consistent molecular mechanics force fields.     

Different spectral signatures of octapeptide 3(10)- and alpha-helices revealed by two-dimensional infrared spectroscopy

Femtosecond two-dimensional infrared (2D IR) spectroscopy is applied to the amide I modes of the terminally protected homo-octapeptide Z-[L-(alphaMe)Val](8)-OtBu in CDCl(3), 2,2,2-trifluoroethanol (TFE), and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) solutions to acquire 2D spectral signatures that distinguish between 3(10)- and alpha-helix structures. Suppression of diagonal peaks by controlling polarizations of IR pulses clearly reveals cross-peak patterns that are crucial for structural determination. A doublet feature is observed when the peptide ester forms a 3(10)-helix in CDCl(3) and TFE and when it is at the initial stage of 3(10)- to alpha-helix transition in HFIP. In contrast, the 2D IR spectrum shows a multiple peak pattern after the peptide ester has acidolyzed and become an alpha-helix in HFIP. Electronic circular dichroism spectra accompanying the acidolysis-driven conformational change are also reported. This is the first report on the experimental 2D IR signature of a 3(10)-helical peptide. These results, using a model octapeptide, demonstrate the powerful capability of 2D IR spectroscopy to discriminate between different helical structures.     

Theoretical study of the Raman optical activity spectra of 3(10)-helical polypeptides

Raman optical activity (ROA) spectroscopy is a promising analytical method for studying the structure and conformation of polypeptides and proteins in solution. However, the structural information obtained from such vibrational spectra is only indirect and theoretical studies are often necessary to identify how the structure determines the observed spectra. One particular target is the identification and discrimination of different helical secondary structure elements. Herein, a theoretical investigation of the ROA spectra of a series of 3(10)-helical polypeptides is presented. In particular, the effect of chain length, C(α)-substitution pattern, the introduction of larger aliphatic side chains, and the variation of their conformation on the ROA spectra is studied. To extract general principles from these calculations, the positions, intensities, and shapes of the ROA bands are analyzed in terms of localized modes, which makes it possible to identify possible ROA signatures of 3(10) -helical structures, but also provides fundamental insight into the generation of ROA signals in complex polypeptides. Finally, the calculated spectra can be compared to the previously reported ROA spectrum of a specifically designed 3(10) -helical heptapeptide. This allows most of the features in the experimental spectrum to be assigned.     

Electron impact mass spectra of 1-methyl-3-(2-benzothiazolylhydrazono)-2-indolinones

A study of the fragmentation of l-methyl-3-(2-benzothiazolylhydrazono)-2-indolinones on electron impact reveals that the major processes involve N? N bond fission and the competing loss of CO from the molecular ion.     

Tautomerism and electron impact mass spectra of pyrimidin-4(3H)- and -4(1H)-ones

A mass spectrometric identification and differentiation of pyrimidin-4(3H)- and -4(1H)-ones was carried out. N-Substitution at position 1 or 3 made the distinction of the two sets of compounds very easy because of their characteristic fragmentation pathways. Most interesting were the spectra of the N-unsubstituted derivatives, which illustrated a predominance of the two possible NH tautomers in relation to the 4-hydroxy structure.     

Theoretical and experimental study of molecular structure and vibrational spectra of N -(2-pyridylmethyl)-2-pyrazinecarboxamide

N-(2-Pyridylmethyl)-2-pyrazinecarboxamide was prepared and its crystal structure was investigated by X-ray analysis. The compound crystallizes in the triclinic space group P[`1]P{\bar 1} with a = 4.262(3), b = 12.117(9), c = 20.840(18) ?, α = 91.802(6), β = 89.834(7), γ = 91.845(6)°, V = 1075.2(16) ?³, Z = 4, and D = 1.323 Mg/m³. The structure was solved by direct method and refined to R = 0.0699 and wR ₂ = 0.1268 by full matrix anisotropic least-squares method. Using the Hartree-Fock and density functional method (B3LYP) with 6-31G(d) basis set, the molecular geometry and vibrational frequencies of the title compound has been investigated and compared with experimental ones from experimental studies. The optimized bond lengths obtained by RHF method and bond angles obtained by B3LYP method show better agreement with the experimental values. The vibrations computed of the title compound by the RHF and DFT methods are in good agreement with the observed IR spectra data.     

Theoretical study of the vibrational spectra of the hydrogen-bonded systems between pyridine-3-carboxamide (nicotinamide) and DMSO

The vibrational characteristics (vibrational frequencies and infrared intensities) for the hydrogen-bonded systems of nicotinamide (NA(Z) and NA(E)) with dimethyl sulfoxide (DMSO) have been predicted using ab initio SCF/6-31G(d,p) and DFT (BLYP/6-311++G(d,p)) calculations. The changes in the vibrational characteristics from free monomers to a complex have been calculated. The ab initio and BLYP calculations show that the complexation between nicotinamide (NA(Z) and NA(E)) and DMSO leads to large red shifts of the stretching vibrations for the hydrogen-bonded N-H bonds of nicotinamide and very strong increase in their IR intensity. The results from the BLYP/6-311++G(d,p) calculations show that the predicted red shifts of the nu(s)(NH) and nu(as)(NH) vibrations for the complex NA(E)-DMSO (1:2) (Deltanu(as)(NH)=-186 cm(-1) and Deltanu(s)(NH)=-198 cm(-1)) are in better agreement with the experimentally measured. The magnitudes of the wavenumber shifts are indicative of strong NH...O hydrogen-bonded interactions in both complexes. The calculations predict an increase of the IR intensity of nu(s)(NH) and nu(as)(NH) vibrations in the complexes up to 14 times. Having in mind that in more cases the predicted changes in the vibrational characteristics for the complexes studied are very near, it could be concluded that both conformers of nicotinamide, Z-conformer and E-conformer, are present in the solution forming the hydrogen-bonded complexes with DMSO.     

Enzyme-catalyzed synthesis of (R)- and (S)-3-hydroxy-3-(10-alkyl-10H-phenothiazin-3-yl)propanoic acids

Starting from the racemic ethyl 3-hydroxy-3-(10-alkyl-10H-phenothiazin-3-yl)propanoates as substrates, a multienzymatic procedure was developed for the efficient synthesis of the corresponding highly enantiomerically enriched (R)- and (S)-3-heteroaryl-3-hydroxypropanoic acids.     

VUV and photoelectronic spectra of methylstannane. Theoretical and experimental approach

The vacuum ultraviolet (VUV) and photoelectron spectra of SnH₃CH₃ were recorded between 6.20 and 11.28 eV and between 8 and 17 eV, respectively. Spectra were interpreted using ab initio CI calculations. The photoelectron spectrum confirmed the low SnC bond energy. The first two ionization potentials (IP) observed were attributed to the ionization of the a₁ (10.65 eV) and e orbitals (11.15 and 11.60 eV, split by the Jahn-Teller effect), thereby showing an inversion of IPs compared with ethane. Similarly, the first two bands of the VUV spectrum (at 7.04 and 7.72–8.16 eV) were attributed to a₁ and e transitions towards the Rydberg s orbital. A splitting of the same order of magnitude as that of the photoelectron spectrum could be noted in the E state. Observed transitions between 8.65 and 10 eV showed a strong interaction between the Rydberg p MO and the σ^*_SnC antibonding orbital. Primarilyvalence transitions were encountered beyond 10 eV.     

Theoretical and experimental studies on the Raman spectra of electrosynthesized polynaphthalene

Polynaphthalene (Pnap) was electrosynthesized through the direct oxidation of naphthalene in boron trifluoride diethyl etherate and was characterized with IR and Raman spectroscopy, matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy, and thermogravimetric analysis. Raman spectra of oligonaphthalene were calculated with Gaussian 98 at the B3LYP/6‐31G* level. Combining the computational and experimental results, we assigned the Raman bands of pristine Pnap. The Raman bands related to the chain‐stretching vibrations of Pnap around 1600 cm^?1 shifted to higher wave numbers as the polymerization degree increased. This phenomenon was in contrast to that of other conducting polymers bearing simple aromatic rings, such as polythiophene and polyfuran. The reason was that the condensed ring of Pnap and the steric repulsion of the interring hydrogen atoms prevented the elongation of conjugation sequences with the polymer chain length. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 241–251, 2005     

The Raman and IR spectra and normal coordinate analysis of 3-(N-phenylacetylamino)-2,6-piperidinedione,Antineoplaston A10, the new antitumour drug

The Raman and IR spectra of 3-(N-phenylacetylamino)-2,6-piperidinedione, Antineoplaston A10, the new antitumour drug and its N,N-dideuterated derivative have been recorded in the range 4000-30 cm⁻¹. Vibrational assignments are given and are supported by normal coordinate calculations based on a general valence force field. The interaction force constants were transferred intact from the scaled ab initio force fields of structurally related molecules. The calculated frequencies are in very good agreement with the experiment. A striking similarity is noted for frequencies of the corresponding vibrations in Antineoplaston A10 and in uracil derivatives. The results obtained support previous theoretical predictions that the mechanism of action of A10 may be related to its structural and electronic resemblance with pyrimidine bases. The drug may act as their antagonist in the electrostatic interaction and hydrogen bonding formation with biological molecules.     

Theoretical study of the adsorption of H on Si n clusters, (n=3-10)

A recently proposed local Fukui function is used to predict the binding site of atomic hydrogen on silicon clusters. To validate the predictions, an extensive search for the more stable SinH (n=3-10) clusters has been done using a modified genetic algorithm. In all cases, the isomer predicted by the Fukui function is found by the search, but it is not always the most stable one. It is discussed that in the cases where the geometrical structure of the bare silicon cluster suffers a considerable change due to the addition of one hydrogen atom, the situation is more complicated and the relaxation effects should be considered.     

Theoretical study on the structures and electronic spectra of TCNE2-.

Investigations into the charge-separated states and electron-transfer transitions in tetracyanoethylene (TCNE) complexes have recently generated much interest. In this work we present theoretical calculations showing that the most stable structure of the dianion TCNE2- has D2d symmetry in vacuum as well as in the solvents dichloromethane and acetonitrile. By means of the coupled cluster linear response, we compute the vertical electronic spectrum in both the gas phase and solution. The theoretical results are compared to the experimental data and good agreement is achieved.     

3-Aryl(hetaryl)-3-hydroxy-2-phosphorus-substituted acrylonitriles. Synthesis and experimental and theoretical conformational analysis

Under conditions of the phase transfer catalysis, acylation of (thio)phosphorylacetonitriles by (het)aroyl chlorides affords the Z-enol forms of C-acylation products in high yields. Their configurations were studied by IR spectroscopy, dipole moment measurements, and ab initio quantum-chemical calculations [B3LYP/6-31G(d)]. The C=C double bond and the phosphoryl or thiophosphoryl group have an s-cis arrangement. The possibility of strong intramolecular hydrogen bonding in these conformers is the governing factor responsible for the three-dimensional structures of the compounds under investigation. Derivatives of nicotinic acid existing in the individual form as zwitterions are the only exceptions.     

Influence of diene substitution on Diels-Alder reactions between vinyl dihydronaphthalenes and (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone

The asymmetric Diels-Alder reaction between 2-(E-2-acetoxyvinyl)-8-tert-butyl-3,4-dihydronaphthalene (8) and enantiopure (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone (1) takes place exclusively on the unsubstituted C(5)-C(6) double bond of (SS)-1 with a very high control of the chemo-, regio-, and diastereoselectivity of the process affording tetracyclic sulfinyl derivative 13a possessing five stereogenic centers. The analogue diene 9, lacking the tert-butyl group, gave a less chemoselective reaction (C(2)-C(3)/C(5)-C(6): 60/40) in favor of reaction through the sulfoxide-substituted double bond C(2)-C(3) of 1. Steric effects of the remote tert-butyl group and electronic factors due to the OAc substituent are controlling the process.     

Conformations of the Ten-membered Ring in 5, 10-Secosteroids. III: (Z)-3β- and (Z)-3α-Hydroxy-5, 10-seco-1 (10)-cholesten-5-one Esters and (Z)-5, 10-seco-1 (10)-Cholestene-3, 5-dione

(Z)-3β-Acetoxy- and (Z)-3 α-acetoxy-5, 10-seco-1 (10)-cholesten-5-one ( 6a ) and ( 7a ) were synthesized by fragmentation of 3β-acetoxy-5α-cholestan-5-ol ( 1 ) and 3α-acetoxy-5β-cholestan-5-ol ( 2 ), respectively, using in both cases the hypoiodite reaction (the lead tetraacetate/iodine version). The 3β-acetate 6a was further transformed, via the 3β-alcohol 6d to the corresponding (Z)-3β-p-bromobenzoate ester 6b and to (Z)-5, 10-seco-1 (10)-cholestene-3, 5-dione ( 8 ) (also obtainable from the 3α-acetate 7a ). The ¹H-and ¹³C-NMR. spectra showed that the (Z)-unsaturated 10-membered ring in all three compounds ( 6a , 7a and 8 ) exists in toluene, in only one conformation of type C ₁, the same as that of the (Z)-3β-p-bromobenzoate 6b in the solid state found by X-ray analysis. The unfavourable relative spatial factors (interdistance and mutual orientation) of the active centres in conformations of type C ₁ are responsible for the absence of intramolecular cyclizations in the (Z)-ketoesters 6 and 7 ( a and c ).     

Electron impact mass spectra of 5,5-bis(carboethoxy)-1,3-dioxanes

Electron impact-induced fragmentations of 2-substituted 5,5-bis(carboethoxy)-l,3-dioxanes were studied by exact mass measurements and metastable ion analysis. The substituent R on C(2) of the heterocyclic ring has little influence on the principal cleavage reactions. Elimination of CH₂O/CO and C₂H₄O/C₂H₄/C₂H₅OH are common fragmentations for ions containing the 1,3-dioxane moiety or the OC₂H₅ group, respectively. The abundant ions at m/z 173 and 127 serve as structural probes for the class of compounds studied. Primary fragmentations implying the ester function are of little importance.