Harmonic analysis of large systems. I. Methodology

Methods have been developed for the determination of vibrational frequencies and normal modes of large systems in the full conformational space (including all degrees of freedom) and in a reduced conformational space (reducing the number of degrees of freedom). The computational method, which includes Hessian generation and storage, full and iterative diagonalization techniques, and the refinement of the results, is presented. A method is given for the quasiharmonic analysis and the reduced basis quasiharmonic analysis. The underlying principle is that from the atomic fluctuations, an effective harmonic force field can be determined relative to the dynamic average structure. Normal mode analysis tools can be used to characterize quasiharmonic modes of vibration. These correspond to conventional normal modes except that anharmonic effects are included. Numerous techniques for the analyses of vibrational frequencies and normal modes are described. Criteria for the analysis of the similarity of low-frequency normal modes is presented. The approach to determining the natural frequencies and normal modes of vibration described here is general and applicable to any large system. © 1995 John Wiley & Sons, Inc.

1 This article is a U.S. Government work and, as such, is in the public domain in the United States of America.

     

Harmonic analysis of large systems. III. Comparison with molecular dynamics

Atomic motions in bovine pancreatic trypsin inhibitor (BPTI), derived from molecular dynamics, harmonic analysis, and quasiharmonic analysis, are compared when a single protein model, energy parameters, and environment are employed. Molecular dynamics (MD) was carried out for 2 nanoseconds. An average structure was determined from the last nanosecond of the MD simulation, when no major structural changes were observed. This structure was used for several harmonic analysis calculations as well as for a reference structure for the quasiharmonic analysis, for both full basis and reduced basis sets. In contrast to the harmonic analysis results, the quasiharmonic reduced basis calculation using a spherical harmonics reduced basis provided good agreement with the full basis calculation, suggesting that when anharmonic effects are considered, BPTI can behave as a homogeneous object. An extensive analysis of the normal modes from a diverse set of 201 minimized MD simulation frames was performed. On only the sub-picosecond time scale were energy minima revisited after a transition to another state. This analysis shows that the dynamics average structure is not representative of the simulation frames in terms of energy and vibrational frequencies. For this model of BPTI, 42% of the motion (mean-squared fluctuation) can be attributed to harmonic limit behavior. A spectral analysis of the correlation function of deformation for a particular normal mode or quasiharmonic mode can be used to determine the time scales of motions which correspond to harmonic vibration, large-scale drift, or sharp transitions between local substrates. © 1995 John Wiley & Sons, Inc.     

Optimized Gaussian basis sets for use with relativistic effective (core) potentials: K,Ca, Ga—Kr

Correlation-consistent valence basis sets were developed for the third-row main block elements (K, Ca, Ga—Kr) for use with relativistic effective core potentials. These basis sets are somewhat larger than double-zeta in size, with polarization functions, and are balanced for use in both Hartree–Fock and correlation calculations. Spin–orbit splittings for atoms and molecules are calculated and compared to experiment. These calculations use the approximate spin–orbit operator from the relativistic effective core potentials. The use of these results in the calculation of accurate thermochemical data is discussed. © 1997 John Wiley & Sons, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

The very low-pressure pyrolysis of phenyl ethyl ether,phenyl allyl ether,and benzyl methyl ether and the enthalpy of formation of the phenoxy radical

A value of the enthalpy of formation of the phenoxy radical in the gas phase, ΔH°_,298K (?O·, g) = 11.4 ± 2.0 kcal/mol, has been obtained from the kinetic study of the unimolecular decompositions of phenyl ethyl ether, phenyl allyl ether, and benzyl methyl ether

1 Trivial names for ethoxy benzene, 2-propenoxy (allyloxy) benzene, and α-methoxytoluene, respectively

at very low pressures. Bond fission, producing phenoxy or benzyl radicals, respectively, is the only mode of decomposition in each case. The present value leads to a bond dissociation energy BDE(?O—H) = 86.5 ± 2 kcal/mol,

2 1 kcal = 4.18674 kJ (absolute)

in good agreement with recent estimates made on the basis of competitive oxidation steps in the liquid phase. A comparison with bond dissociation energies of aliphatic alcohols, BDE(RO—H) = 104 kcal/mol, reveals that the stabilization energy of the phenoxy radical (17.5 kcal/mol) is considerably greater than the one observed for the isoelectronic benzyl radical (13.2 kcal/mol). Decomposition of phenoxy radicals into cyclopentadienyl radicals and CO has been observed at temperatures above 1000°K, and a mechanism for this reaction is proposed.     

New spherical-cutoff methods for long-range forces in macromolecular simulation

New atom- and group-based spherical-cutoff methods have been developed for the treatment of nonbonded interactions in molecular dynamics (MD) simulation. A new atom-based method, force switching, leaves short-range forces unaltered by adding a constant to the potential energy, switching forces smoothly to zero over a specified range. A simple improvement to group-based cutoffs is presented: Switched group-shifting shifts the group–group potential energy by a constant before being switched smoothly to zero. Also introduced are generalizations of atom-based force shifting, which adds a constant to the Coulomb force between two charges. These new approaches are compared to existing methods by evaluating the energy of a model hydrogen-bonding system consisting of two N-methyl acetamide molecules and by full MD simulation. Thirty-five 150 ps simulations of carboxymyoglobin (MbCO) hydrated by 350 water molecules indicate that the new methods and atom-based shifting are each able to approximate no-cutoff results when a cutoff at or beyond 12 Å is used. However, atom-based potential-energy switching and truncation unacceptably contaminate group–group electrostatic interactions. Group-based potential truncation should not be used in the presence of explicit water or other mobile electrostatic dipoles because energy is not a state function with this method, resulting in severe heating (about 4 K/ps in the simulations of hydrated MbCO). The distance-dependent dielectric (? ∝? r) is found to alter the temperature dependence of protein dynamics, suppressing anharmonic motion at high temperatures. Force switching and force shifting are the best atom-based spherical cutoffs, whereas switched group-shifting is the preferred group-based method. To achieve realistic simulations, increasing the cutoff distance from 7.5 to 12 Å or beyond is much more important than the differences among the three best cutoff methods. © 1994 by John Wiley & Sons, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

The Binding of Flavins by Apoflavodoxins from Peptostreptococcus elsdenii and Azotobacter vinelandii as Studied by Temperature-Jump Technique

The binding of various flavins by apoflavodoxins from P. elsdenii and A. vinelandii has been studied by the temperature-jump technique using fluorescence detection. P. elsdenii apoflavodoxin interacts only with flavins possessing 5 carbon atoms in the N(10) side chain and a terminal phosphate group. Employing a wide range of concentrations of deoxy-FMN

1 Flavin = 3,4-dimethyl-lO-substituted isoalloxazine = 3,4-dimethyl- lO-substituted-2,3,4,10-tetrahydro-benzo[g]-pteridine-2,4-dione; FMN = riboflavin-5′-monophosphate.

and apoflavodoxin only one relaxation process was observed, indicating a one-step binding mechanism. With native flavodoxin no relaxation could be observed. The kinetic parameters of the interaction of A. vinelandii apoflavodoxin with various flavin analogs (Structure I ) have also been investigated. The interaction between apoflavodoxin and flavin derivatives carrying an ionizable, terminal functional group on the side chain becomes very weak when the number of the side chain carbon atoms is decreased below 4. This observation is interpreted in terms of repulsive forces due to negatively charged amino acid residues located in the flavin side chain binding region of the apoflavodoxin. All complexes studied revealed only one relaxation process. This observation is in contradiction with published results [10]. The published traces are instrumental artifacts.     

Cationic initiation of oligomerization of vinylformamide

Vinylformamide (VFA) is cationically polymerized in various solvents at 273 K and reaction temperature by the following initiators: iodine, bis(4-methoxyphenyl)-methyl chloride/silica, triphenylmethyl chloride/silica, and trimethylsilyl triflate. In every case defined oligomers with narrow molecular weight distribution are obtained in moderate yield (20–50%). Acid hydrolysis of the obtained oligomers yields well defined oligovinylamine products. The cationic initiation mechanism of VFA is discussed in terms of the HSAB-concept

1 HSAB: Hard and soft acids and bases.

     

Gas chromatographic—mass spectrometric studies of long chain hydroxy acids.—III.1 The mass spectra of the methyl esters trimethylsilyl ethers of aliphatic hydroxy acids. A facile method of double bond location

Trimethylsilylation has proved to be extremely useful in the gas chromatography and the mass spectrometry of hydroxy acid methyl esters. The characteristic mass spectral fragmentation patterns have shown these derivatives to be superior in some respects to others for structural elucidation; in particular, hydroxylation followed by trimethylsilylation provides a useful method of double bond location in unsaturated fatty acid esters.

1 A preliminary presentation of this method has been given by G. Eglinton at the Lecture etting in Combined Gas Chromatography—Mass Spectrometry at the school of Pharmacy, London, August 9, 1967. It has come to the authors' attention that this method simultaneously developed by Dr. P. Capella, Institute di Industria Agrarie, University of Bologna, Italy^1c (P. Capella and C. M. Zorzut, Anal. Chem. 41 , 1458 (1968).)

     

Novel Porphyrinoids for Chemistry and Medicine by Biomimetic Syntheses

In 1926 Hans Fischer and Bruno Walach synthesized the first porphyrins.

1 H. Fischer, B. Walach, Justus Liebigs Ann. Chem. 1926 , 450, 164–181.

Currently more than 1400 new articles concerning the synthesis and uses of porphyrins are published every year.

2 CAS Online search for 1994 .

However, the strong interest in these compounds indicated by this is in sharp contrast to their restricted availability. This is reflected in the current price of up to 500 DM for 5 mg of the most important porphyrins used in research and other applications (see Scheme 3). Biomimetic syntheses offer possibilities for an improved approach to porphyrins. By following the example set by nature it is also possible to obtain novel porphyrinoids which are different from naturally occurring porphyrins. This is exemplified by N,N′-bridged porphyrinogens, which have cage structures, inverted porphyrinoids (N atoms in the outer periphery) and, in particular, porphyrins with expanded systems. Among the family of expanded porphyrins are superarenes with up to 34 π electrons. Their pronounced aromaticity is indicated by ¹H NMR spectra, bond length equivalence, planar structures, and electrophilic substitution. With their strong absorption bands, the strongest of which have ? values of > 1000000, a value which exceeds the absorption intensity of all other organic pigments observed until now, and their ability to act as efficient photosensitizers, the expanded porphyrins open interesting perspectives in the fields of photochemistry and photomedicine.     

Chemie von α-Aminonitrilen. 12. Mitteilung. Sondierungen über thermische Umwandlungen von α-Aminonitrilen

Chemistry of α-Amino Nitriles

1 11. Mitteilung: [1].

. Exploratory Experiments on Thermal Reactions of α-Amino Nitriles The paper extends a previously published report [4] on chemical properties of α-amino nitriles and of members of the C₃H₄N₂ ensemble (Scheme 1) as observed in experiments carried out under non-aqueous conditions. The reactions investigated and the observations made are summarized in some detail in the English footnotes (*) referring to Schemes 1–17 and Fig. 1.     

On Cardioactive Steroids. VIII. The Synthesis of Bufalin and Resibufogenin Isomers

α-Isobufalin

1 Systematic names are given at the titles of the Exper. Part.

( 1 ) and β-isoresibufogenin ( 3 ) have been synthesized from testosterone by a method which features a novel oxidative furan to pyrone transformation.     

Tertiary Phosphane/Tetrachloromethane,a Versatile Reagent for Chlorination,Dehydration, and P?N Linkage

In this review the processes occurring on the treatment of triphenylphosphane with tetrachloromethane are first reported; a key role is played here by (trichloromethyl)phosphonium chloride which reacts with a further amount of the phosphane to give the stable salt [chloro(triphenylphos-phoranediyl)methyl]triphenylphosphonium chloride by way of dichlorophosphorane and (dichloromethylene)phosphorane that is detectable only as an intermediate. The preparative application of the two-component system as a chlorinating, dehydrating, and P—N-linking reagent is ascribable to “phosphorylation”

1 Here and below, “phosphorylation” is used lo mean in general the formation of a phosphorus derivative. In the narrower sense this term denotes the introduction of phosphoryl groups P(O).

of the substrate in question through several reactive species. In these applications the reactions with the substrate compete with reactions of the two-component system with itself, so that the overall course of the reaction is in nearly all cases much more complex than was previously assumed. Nevertheless. very good results can be achieved by the use of this reagent, high yields and mild reaction conditions being characteristic.     

Reactions of the Carbonyl Group in Fluorinated Ketones

The chemistry of polyfluorinated ketones has recently received a great deal of attention.

1 A. Ya. Yakoubovich, Usp. Chim. 25, 3 (1956).

2 H. P. Braendlin and E. T. McBee in: Advances in Fluorine Chemistry. Butterworths, London 1963, Vol. 3, p. 1.

3 The review by Braendlin and McBee [2] does not deal only with perfluorinated ketones; moreover, though published in 1963, it is already outdated. The papers discussed in [1,2] will not be reviewed in the present article.

. The carbonyl and imino groups of the fluorinated ketones and their imines react in many different ways. In particular, the electron-attracting perfluoroalkyl groups intensify the electrophilic properties and weaken the nucleophilic properties of the carbonyl group. The perfluoroalkyl group also hinders the heterolytic removal of the hydroxyl group from adducts by reducing the stability of the carbonium ion . The increased electrophilicity of the carbonyl group and the increased stability of the addition products leads not only to a change in reactivity in the characteristic ketone reactions, but also to numerous new reactions which are not observed with non-fluorinated ketones. Thus it is possible to synthesize a wide variety of fluoroorganic compounds from perfluorinated ketones.

4 We have been concerned mainly with hexafluoroacetone, since in addition to being the most readily available and simplest perfluorinated ketone, this is also a typical representative of this class of compounds.

.     

Reversible protection of oligomeric ethylene glycols by bis (2,4-dinitrophenylation) and basic ethanolysis

Bis-(2,4-dinitrophenyl)glycols are stable in the presence of triethylamine but undergo ethanolysis in the presence of hydroxide ions. The quantitative removal of the DNP blocking group allows an integrated scheme to pure glycols from commercially available polyethylene glycol mixtures

1 Mixtures of ethylene glycol oligomers are obtained by anionic polymerization of ethylene oxide. See, for example, G. O. Curme and F. Johnston, Glycols, Reinhold, New York, 1953. They are commercially available (as PEG-200, PEG-400, etc., to indicate the average molecular weight of the major components).

by bis-dinitrophenylation, chromatographic separation, and end-group removal, using high performance liquid chromatography (HPLC) of the bis-(2,4-dinitrophenyl)glycols for purity monitoring. A facile synthetic method for the production of penta-to dodecaglycols in a mixed, aqueous, dioxane solvent system, with fair yields, is also described. The bis-(2,4-dintrophenyl) protection of glycols is a reversible reaction that can be used as (1) a preparative method for pure glycols from readily available commercial polyethylene glycol mixtures; (2) a highly sensitive and accurate analytical method

2 A. Warshawsky, A. Tishbee, and N. Shoef, J. Liq. Chromatogr., submitted for publication.

coupled with HPLC.     

Heterocyclic Spiro-naphthalenones. Part V. Synthesis of Some 2-Benzazepines from 3,4-Dihydrospiro [furan-2-(5H), 1′(2′H)-naphthalene]-2,5-dione

Compound 2 was rearranged on treatment with 2N NaOH to the 2-benzazepine-3-propanoic

1 See footnote (5) of the preceding paper.

acid 3 . Some aspects of the chemistry of this acid were studied.     

(Perhalogenmethylthio)heterocyclen. XII. Herstellung von Perfluoroalkylsulfonylharnstoff-Derivaten sowie CCl3−nFnX-substituierten Heterocyclen und deren biologische Wirkung

(Perhalomethylthio)heterocycles XII. Preparation of Perfluoroalkylsulfonylurea Derivatives as well as CCl_3?nF_nX-Substituted Heterocycles and Their Biological Activity

1 XI, Mitt., s.[1]

In the presence of CF₃SO₃H (chlorodifluoromethylthio)thiophene 1 reacts with CClF₂SCl to give the 2,5-disubstituted thiophene 2a which on oxidation with 30% H₂O₂-solution yields the corresponding sulfonyl compound 2b · R¹SO₂NCO adds amines to give R¹SO₂NHC(O)NHR 3a – g . Some biological properties of these compounds were investigated.     

The site of radical attack at the furan ring from MNDO calculations

The semi-empirical SCF MNDO method has been used to calculate the radical reactivities for each reaction site in some neutral furan molecules as the average of the HOMO and LUMO probabilities both in 2p_z atomic orbitals 1

1 SCF: Self-consistent field; MNDO: modified neglect of differential overlap; HOMO: highest occupied molecular orbital; LUMO: lowest unoccupied molecular orbital.

. The carbon atoms C⁵ and C² of of the furan ring are the most favoured sites except for the furan derivatives holding a double bond in the substituent group. Also the SOMO 2

2 SOMO: Single occupied molecular orbital.

probabilities of the radicals formed by addition of a hydrogen atom or a vinyl acetate model radical were calculated. Thus, once a radical is added to the C⁵ position the resulting radical can be partially localized on the carbon C². Furthermore, the enthalpy of reaction for several radicals was estimated by using the calculated heats of formation of the neutral furan molecules and their radicals. The radical addition to the carbon C ⁵ resulted in the most exothermic reaction in comparison with other reaction sites of the molecule. However, no correlation was found between the calculated enthalpies and the degradative-transfer kinetic constants experimentally determined for the radical polymerization of vinyl acetate in the presence of the furan compounds under study.     

Interfacial tension measurement with the neumann triangle method

The interfacial tensions between polystyrene (PS) and poly(butylene terephthalate)

1 System. name: poly(tetramethylene terephthalate).

(PBT), PS/poly(methyl methacrylate) (PMMA), and PBT/PMMA pairs have been obtained by employing the Neumann Triangle method (NT). The results are in good agreement with those obtained by the breaking thread method. For the first time, the NT method was applied to a reactive polymer pair with an in-situ compatibilizer to measure the interfacial tension. We found that the interfacial tension of the PS/PBT system with a small amount of poly(styrene-co-glycidyl methacrylate)

2 System. name of glycidyl: 2,3-epoxypropyl.

(PS-GMA) is significantly reduced compared to that without PS-GMA.     

Structure et synthèse de la damascénone (triméthyl-2,6,6-trans-crotonoyl-1-cyclohexadiène-1,3), constituant odorant de l'essence de rose bulgare (rosa damascena Mill.

Damascenone

1 DORICENONE (trade mark applied for by Firmenich & Cie, Geneva).

an odoriferous ketone isolated in minute amounts from Bulgarian rose oil (Rosa damascena Mill.) is shown to be trans-2,6,6-trimethyl-1-crotonoyl-cyclohexa-1, 3-diene (I). A synthesis starting from beta;-cyclocitral is described for this conspicuous constituent of rose oil, which displays a powerful fragrance. The synthesis of four related, more saturated ketones, damascones

2 DORINONE (trade mark applied for by Firmenich & Cie, Geneva).

, is also described.