Showing papers on "Steric effects published in 1981"

Stereochemistry of Nucleophilic Addition to Cyclohexanone. The Importance of Two-Electron Stabilizing Interactions

Abstract: A theory of charge-transfer stabilization of the transition state for nucleophilic addition to a carbonyl group by electron donors is proposed. It is postulated, using the Bell-Evans-Polanyi principle, that the feature of this transition state critical for stereoselectivity of the reaction is the existence of a low-lying vacant orbital u** associated with the u bond being formed in the reaction and that electron delocalization into that orbital will stabilize the transition state and may thereby enhance the reaction rate: the kinetic anomeric effect and the kinetic a effect are considered as the examples of such a stabilizing interaction. Stereochemistry of nucleophilic addition to cyclohexanone is determined by two factors according to this model: steric hindrance which favors the equatorial approach and electron donation from the cyclohexanone ucc and ucH bonds into the u** orbital, which favors the axial approach since the carbon-hydrogen bonds are better electron donors. Consequently, nucleophile structure, metal cations complexing the carbonyl oxygen, solvent, and counterions or other solutes may influence stereoselectivity of the reaction by changing the e(.**). Furthermore, it is shown that this model offers a simple and consistent way to rationalize kinetic and stereochemical effects of the so-called "remote polar substituents" which cannot be explained in terms of steric or electrostatic interactions but appear to be controlled by the overlap and energy gap between the remote electron-donor orbitals and the u** orbital.

Neutron diffraction reveals oxygen-histidine hydrogen bond in oxymyoglobin.

Abstract: Myoglobin (Mb) reversibly binds molecular oxygen in vertebrate muscle and consists of a polypeptide chain of 153 residues and one haem, which closely resembles one subunit of a haemoglobin (Hb) tetramer. In oxygenated myglobin (oxyMb) the iron atom is coordinated by four porphyrin nitrogen atoms, Ne of the invariant ‘proximal’ histidine (F8), and molecular oxygen1. The oxygen molecule lies in a tight pocket, bounded by two hydrophobic groups (Phe CD1 Val E11) and the side chain of the ‘distal’ histidine (E7). This histidine is present in Hb and Mb of many different organisms, with substitution by glutamine or leucine found in only a few cases. The function of the residue is not clear, although it does present steric hindrance to linear ligands such as carbon monoxide and favours ‘bent’ ones, such as O2. We report here that the imidazole stabilizes bound molecular oxygen with a hydrogen bond, as revealed by neutron diffraction analysis.

Transport and reactivity of hydrocarbon molecules in a shape-selective zeolite

Abstract: For the catalytic cracking of C6 to C9 hydrocarbons on ZSM-5, we demonstrate quantitatively the contributions of each of two mechanisms for molecular shape selectivity. Using crystallites of different sizes and activities, and classical methods for evaluating diffusion inhibition of the reaction rate, we separate the effects of mass-transport-induced selectivity from that created by steric inhibition by the size of a reaction complex. The selective cracking of n-paraffins compared to monomethyl paraffins (from C6 to C9) is due to a higher intrinsic rate constant of the n-paraffin, with diffusional mass transport playing no appreciable role. In contrast, dimethyl paraffin cracking is strongly diffusion-inhibited. The methyl paraffin/n-paraffin discrimination is a result of steric constraint on the sizeable methyl paraffin/carbonium ion reaction complex. This structural selectivity is shown to be absent for the corresponding olefins where such complexes do not arise. The diffusivities at reaction conditions have been determined. For the linear hydrocarbon, diffusivity notably exceeds that expected from the Knudsen model. This reminds us to review assumptions of conventional concepts of mass transport. The availability of zeolites now allows us to probe many basic phenomena in catalysis, molecular configuration and dynamics, including mass transport.

Potential antitumor agents. 34. Quantitative relationships between DNA binding and molecular structure for 9-anilinoacridines substituted in the anilino ring

Abstract: In an investigation of the structure-activity relationships in the 4'-(9-acridinylamino)methanesulfonanilide (AMSA) tumor inhibitory analogues, the DNA-binding properties of a series of simple 9-anilinoacridines were examined. Positional numbering as in the AMSA series has been employed. DNA binding was determined by drug competition with the fluorochrome ethidium for available sites. The decrease in fluorescence of a DNA-ethidium complex by the addition of drug is due to both drug displacement of bound ethidium and quenching of the fluorescence of bound ethidium by bound drug; measurement of both factors allows drug-DNA association constants (K) to be determined. DNA binding is augmented by 1' or 2' electron donor substituents, and significant correlation equations have been derived with Hammett's sigma p or sigma m constants. Group molar refractivity (MR) for 1'-substituents is an additional significant regression equation term for binding, while the values for 2' and 3' groups play no significant role. Most 3'-substituents decrease binding, presumably as a result of steric inhibition of entry of the acridine nucleus into intercalation sites. A 3'-NHSO2CH3 and 3'-NHCOCH3 substituent confer selectivity of binding to poly[d(G-C)] and poly[d(A-T)], respectively. It is suggested that a combination of H-bond formation and stereochemical features, coupled with steric hindrance, provides the selectivity observed. Binding data are consistent with a model in which the acridine nucleus occupies an intercalation site and the noncoplanar 9-anilino ring resides in the DNA minor groove.

The Chemistry of the Thermal Degradation of Zinc Dialkyldithiophosphate Additives

Abstract: A mechanism for the thermal decomposition of zinc dialkyldithiophosphate additives has been proposed that accounts for the major degradation products and their dependence on the nature of the alkyl group. The proposed mechanism generally follows well-known rules of phosphorus chemistry. The major points are as follows. (1) The decomposition is initiated by a general migration of alkyl groups from oxygen atoms to sulfur atoms. The rate of this reaction is governed by the ease with which nucleophilic substitution can take place at the α-carbon atom of the alkyl group. The well-established correlation between decreasing number of β-hydrogen atoms and increasing thermal stability is, therefore, explicable in terms of increasing steric hindrance, by the β-subtituents, of nucleophilic attack on the α-carbon atom. (2) Olefin elimination successfully competes with substitution where the alkyl group structure is favorable (i.e. secondary alkyl groups), leading to the formation of phosphorus acids. (3) Nucleophilic...

Bonding in metal-borohydride complexes

Abstract: From the tabulation it appears that an ionic radius of approx. 1.6 +- 0.1 A can be assigned to the borohydride ligand when it forms a bidentate bridge to the metal atom and approx. 1.36 +- 0.06 A when it forms a tridentate bridge to the metal atom. The difference in energy between the various possible modes of bonding is small, and the coordination number of the metal ion and the steric hindrance by other ligands appear to determine which mode of attachment will prevail for the borohydride ligand.

The separation of polar and steric effects. Part 14. Kinetics of the reactions of benzoic acid and of ortho-substituted benzoic acids with diazodiphenylmethane in various alcohols

Abstract: The main results now discussed are rate coefficients for the reactions of benzoic acid and 32 ortho-substituted benzoic acids with diazodiphenylmethane (DDM) at 30.0 °C in 11 alcohols including 2-methoxyethanol. The reaction involves a rate-determining proton transfer. The results have been subjected to correlation analysis in two ways. (a) For the reactions of a given acid in the various alcohols, the log k values are correlated through multiple regression on appropriate solvent parameters. (b) For reactions in a given alcohol, the log k values for the various acids are correlated by using the appropriate form of the extended Hammett equation involving inductive, resonance, and steric parameters. Analyses of type (a), as in earlier work, involve the σ* value of the group R in the alcohol ROH, the Kirkwood function of dielectric constant, f(Iµ)=(Iµ– 1)/(2Iµ+ 1) and nγH, the number of hydrogen atoms in the γ-position in the alcohol. These correlations yield information on the influence of ortho-substituents on the relative importance of specific and non-specific solvent effects. In analyses of type (b) the correlation equations are established with a limited set of substituents (up to 18), whose characteristic parameters σI, σR, and v(determined by Charton) are well established, and are unlikely to show effects due to hydrogen-bonding or substituent conformation. The results for other substituents are then interpreted by comparing log k(calc). from a correlation expression with log k(obs.).

Steric accessibility of reactive centers in B‐DNA

Abstract: A method for calculating the “static” steric accessibilities of atoms within macromolecules for various probes is presented and an application is made to the accessibility of atoms within B-DNA. Changes in accessibility in passing from the individual subunits of the nucleic acid to a single helical strand and then to a double helix are discussed. The influence of various base sequences is also investigated. The present methodology and results are compared to earlier attempts at the calculation of steric accessibilities and their significance for the interpretation of chemical reactivity is substantiated by an illustrative example.

The molecular electrostatic potential and steric accessibility of A-DNA

Abstract: The molecular electrostatic potential and steric accessibility of A-DNA are computed for base sequences (dG.dC)n and (dA.dT)n. An interpretation of the results in terms of the structure of A-DNA is provided and differences with respect to other forms of DNA, namely B-DNA and Z-DNA, are discussed.

Dependence of the γ carbon‐13 shielding effect on the dihedral angle

Abstract: The γ effects on 13C shielding have been examined for a series of rigid molecules containing the substituents CH3, OH, NH2, F, Cl, Br or I. Plots of the γ effect vs the CC-αC-βX dihedral angle are well scattered if the plots do not distinguish modes of substitution. For the series in which the resonating carbon is CH2, however, fairly linear correlations are observed for XCH3, OH, NH2, Cl and Br. It is concluded that within a structurally defined and substitutionally homogeneous series, there is a reasonably linear stereochemical dependence. Although substitution at C-α does not seriously alter the linear relationship, hybridization of the intermediate carbons may be important. The slopes of the plots for the γ effect vs dihedral angle are remarkably similar. Neither a strictly steric (van der Waals) nor a strictly polar source can be the cause of the linear relationship, since our series of substituents ranges widely with respect to both size and electronegativity. The only two factors that are constant within the series are the removal of the hydrogen atom (CCCH to CCCX) and the addition of the bonding and nonbonding orbitals on X that were not present on H.

Reduction by a Model of NAD(P)H. 33. Steric and Electronic Effects on Asymmetric Reduction of 2-Acylpyridines

Abstract: Series of alkyl and fluorinated alkyl 2-pyridinyl ketones have been reduced by a chiral NAD(P)H-model (Me2PNPH) in the presence of magnesium ion in acetonitrile. Optical yield decreases in the order of substituent: CH3>C2H5>C(CH3)3>CH(CH3)2 and CH3>CH2F>CHF2>CF3. The results have been interpreted in terms of conformation of the substrates for alkyl 2-pyridinyl ketones and of electronic competitional effect between two substituents for fluorinated alkyl 2-pyridinyl ketones. Magnesium ion freezes intermolecular arrangement at the transition state of the reduction.

Phosphorus-31 nuclear magnetic resonance as a method of predicting ligand basicity and rates of homogeneous catalysis

Abstract: Variations in CPC bond angles caused by bulky substituents on phosophines change the shielding on the phosphorus nucleus and can often mask correlations between chemical reactivity and /sup 31/P NMR chemical shifts. With use of the chemical shift of the tetrahedral oxide of the parent compound the steric effects are minimized, thus allowing the chemical shift to provide successful correlations with the reactivity of the parent compound. Group contribution effects of the substituents attached to phosphorus suggest a new linear free energy relationship, and the direct relationship between reactivity and chemical shift of the phosphine oxide can aid in the choice of ligands for homogeneous catalysis. The correlations of the chemical shift of the phosphine oxides with ligand basicity and infrared and NMR data of metal-phosphine complexes indicate the influence of both sigma and ..pi.. bonding between the metal and the phosphine ligands.

High field nuclear magnetic resonance spectra of hydroxyl protons of aldoses and ketoses

Abstract: The hydroxyl protons of 23 monosaccharides in their pyranoid from (α or β) are examined by proton NMR at 250 MHz in DMSO-d6 solutions. Intramolecular hydrogen bonding in sugar anions seems to be the major factor in accounting for the lack of parallelism between the pK values and the chemical shifts of the anomeric protons. Another important factor is the possibility of steric hindrance to the solvation of the acidic hydroxyls by the basic DMSO solvent molecules. Equatorial hydroxyls have, as a general rule, lower field chemical shifts (with some exceptions) and larger vicinal HOCH coupling constants, 3J, than axial hydroxyls. Moreover, equatorial hydroxyls are sensitive to the equatorial or axial position of their neighbours, in sharp contrast with axial hydroxyls. Long-range 4J couplings are observed whenever a zig-zag arrangement but a necessary condition is a simultaneous axial position of the OH and CH bonds in the above fragment. In this case, the combined use of vicinal (Karplus-type equation) and long-range coupling constants allows the description of the stereochemistry of the OH bond in a semiquantitative fashion.

Fluorinated lignands in HPLC

Abstract: The chromatographic behaviour of C6F5(CH2)3SiCl3, C6H5(CH2)3SiCl3, CF3(CF2)7CH2CH2SiCl3 and n-C10H21SiCl3 as well as the bonding of these ligands to silica is described. Phases with partially fluorinated ligands show entirely different chromatographic characteristics to analogous phases, where hydrogen replaces fluorine. The silica with the pentafluorophenyl-3-n-propyl-C6F5(CH2)3-ligand has higher k′-values and a better selectivity for aromatic hydrocarbons than that with phenyl-3-n-propyl C6H5(CH2)3-groups, whereas the phase with the fluorinated carbon chain is less useful than the silica modified with n-decyltrichlorosilane n-C10H21SiCl3. The first effect can be explained by complex formation, and the second may be due to a different contact area between the ligand and the solute. The normal hydrocarbon chains hinder each other sterically and expose many adsorption sites, in contrast the perfluorinated chains are sterically fixed and are the first example of “real brushes” in HPLC.