Showing papers on "Steric effects published in 1974"

Cytochrome P-450 difference spectra: effect of chemical structure on type II spectra in mouse hepatic microsomes.

Abstract: A comprehensive study of the relationship between chemical structure and binding was made with mouse hepatic microsomes The generally reported type II spectrum (peak 424-435 nm, trough 390-410 nm) is correlated with the presence of a nitrogen atom in which sp2 or sp3 nonbonded electrons are "sterically accessible" Structural series showed that as substituents are placed closer to this nitrogen, spectral size is either reduced or eliminated Other nucleophilic atoms with relatively free steric access may also cause a modified type II binding ie, a bathochromic shift Data are also presented to show that minor structural changes affect both size and type of spectrum

13C Nuclear Magnetic Resonance Studies. 34. The 13C Spectra of Several Methylcyclopentanones and -cyclohexanones

Abstract: The 13C spectra of 16 methyl substituted cyclohexanones and 15 methylcyclopentanones have been determined. These series were chosen as model systems for the study of steric and conformation effects...

The Mechanism of the Transition Metal-catalyzed Reaction of 1,1′-Carbonyldipyrazoles with Aldehydes and Ketones

Abstract: The metal-catalyzed reaction of 1,1′-carbonyldipyrazoles with aldehydes or ketones to give 1,1′-alkylidenedipyrazoles and carbon dioxide, the latter being derived from the amide carbonyl group as shown by labeling experiments, is sensitive to electronic and to steric substituent effects. Under comparable reaction conditions, 1,1′-carbonyldiimidazole, N-acetylpyrazole, and 1-pyrazole-N,N-diethylcarbonamide do not react with acetone while pyrazole-1-carbo(N′-phenylhydrazide) yields an anilino isocyanate dimer. These results are interpreted in terms of a mechanism that involves coordination of the metal ion at the 2,2′-nitrogen atoms of the pyrazole rings and heterolytic cleavage of an amide bond, followed by formation of a carbamate intermediate, decarboxylation, and metal ion exchange. Unsymmetrically substituted 1,1′-carbonyldipyrazoles were found to equilibrate thermally with their respective symmetrical analogs by an intermolecular exchange mechanism.

A Carbon-13 Nuclear Magnetic Resonance Investigation of Some Substituted Methyl Phenyl Sulfides, Sulfoxides, and Sulfones

Abstract: Carbon-13 chemical shifts for 33 methyl phenyl sulfides, sulfoxides, and sulfones are reported. Observed trends are discussed in terms of the steric and electronic influences of the substituent gro...

E–Z-isomerism in aldimines

Abstract: A range of ortho-disubstituted C-aryl aldimines has been synthesized. N.m.r. spectroscopic analysis revealed a significant proportion of the Z-isomer at equilibrium in solution. The E–Z-isomer distribution is critically examined in terms of electronic, steric, and solvent effects. The effect of trace amounts of carboxylic acid on imine stereomutation is discussed.

Some Stereochemical Implications of the Molecular Conformation of Collagen

Abstract: A space-filling model of collagen has been constructed in accordance with the conformation found for (Gly.Pro.Pro)n. The model shows that leucyl and phenylalanyl residues can be easily accommodated at position X of the collagen tripeptide sequence Gly.X.Y, but are severely constrained by steric hindrance at position Y. Examination of the model has also led to the suggestion that hydrogen bonding of hydroxyproline OH through a water molecule to glycyl CO on the same polypeptide chain might account for the stabilisation of the triple helix conformation by hydroxyproline.

Carbon-13 Nuclear Magnetic Resonance Studies of ortho-Substituted Anisoles and Diphenyl Ethers

Abstract: Carbon-13 n.m.r. chemical shifts for 8 anisoles and 15 diphenyl ethers are reported. para-Carbon shieldings are found to be sensitive to the degree of steric interference to conjugative electron re...

Conformational studies on the hypothalamic thyrotropin releasing factor and related compounds by 1-H nuclear magnetic resonance spectroscopy.

Abstract: Proton magnetic resonance studies at 220 MHz were carried out on the hypothalamic thyrotropin releasing factor (TRF) and a variety of synthetic analogs designed to yield specific information about side chain–side chain and side chain–backbone interactions. The results show that the very low field resonance position of one of the carboxamide protons observed for TRF dissolved in dimethylsulfoxide is neither caused by a seven-membered nor by a ten-membered hydrogen bonded ring, but rather is due to a short range interaction between the unprotonated histidyl side chain and the carboxamide residue. A systematic study of the preferred histidyl side chain conformation in various TRF analogs is in good agreement with this interpretation. It was demonstrated that this interaction is not strong enough to cause significant changes in the preferred back bone conformation of the hormone. The possibilities for typical dipole–dipole interaction are discussed. No such interaction has been detected in TRF dissolved in water. We conclude that the tertiary structure of TRF in polar solvents is determined primarily by the steric characteristics of the bulky side chains which maintain the molecule preferentially in an extended conformation.

Spectra of synthetic zeolites containing transition metal ions. V.* Π complexes of olefins and acetylene with Co(II)A molecular sieve

Abstract: The electronic spectra of the cobalt(II) ion in anhydrous cobalt(II) zeolite A in the presence of adsorbed unsaturated hydrocarbons demonstrate that olefins and acetylene are π bonded to cobalt in well defined surface complexes. Gravimetric adsorption data show that one ethylene molecule is bound by each cobalt ion with an energy of about −68 kJ mol−1. Theoretical analysis treating the unsaturated hydrocarbon as a low symmetry electrostatic perturbation to a tetrahedral Co(II) ion gives a quantitative interpretation of the band splitting in the electronic spectra. This splitting is distinguished from that occurring through the dynamic Jahn‐Teller effect in purely tetrahedral Co(II) complexes. The low symmetry field contributions to the ligand field stabilization energies have been determined from the fine structure in the experimental spectra and have been found to decrease from ethylene to trans‐2‐butene in accord with increasing steric hindrance from substitutional methyl groups. These contributions are...

Crystal structure of polyisobutylene

Abstract: The crystal structure of polyisobutylene was determined by x-ray analysis. The orthorhombic cell, with a = 6.88 A, b = 11.91 A, c (fiber axis) = 18.60 A (space group: P212121 − D), contains two molecular chains each consisting of eight monomeric units in the fiber identity period. The chain conformation is essentially an (8/3) helix, but deviates appreciably from the exact (8/3) helix symmetry. The symmetry of the molecular chain is only a twofold screw axis in exact sense, and a crystallographic asymmetric unit consists of four monomeric units. The torsional angles are where M denotes the methyl group. The averaged skeletal CCH2C and CCM2C bond angles are 128° and 110°, respectively. The large CCH2C bond angles may be due to steric respulsion between the adjacent methyl groups, giving intramolecular distances larger than 3.09 A.

Carbon-13 nuclear magnetic resonance spectra of some substituted pyrroles

Abstract: The 13C n.m.r. spectra of 55 pyrroles have been recorded and assigned. The pyrrole ring carbon chemical shifts can be predicted, to ca. 0·5 p.p.m., on the basis of additive substituent effects together with contributions due to adjacent substituents (steric compression shifts) and in the case of carbonyl functions in the α-positions, an additional ‘conjugation effect’. The substituent chemical shift parameters obtained are analogous to those for substituted thiophens, and are compared with those obtained from ethylenes and benzene derivatives. The C(2) substituents affect mainly C(3) and C(5)(apart from the directly bonded carbon) and the C(3) substituents mainly C(2), and these directive effects may be rationalised by accepted resonance considerations. The steric compression effects parallel those found for other aromatic and olefinic systems; a buttressing effect of the next-but-one substituent was also identified. Novel conjugation effects were manifest for two α-carbonyl substituents at all the ring carbons.

Photochemical reactions. Part II. Cycloaddition reactions with photoenols from 2-methylbenzaldehyde and related systems

Abstract: On photolysis, 2-methylbenzaldehyde can form the corresponding (E)-photoenol which can be trapped with dienophiles in a highly stereoselective manner Maleic anhydride gives a single adduct (11), the reactions of which have been studied From trapping experiments no evidence for the formation of (Z)-photoenol intermediates could be found Ketones which cannot form (E)-photoenols for steric reasons do not form (Z)-photoenols Both 2-benzylbenzaldehyde and 2-methylbenzoyl cyanide can undergo photoenolisation upon irradiation

Control of modes of intramolecular imidazole catalysis of ester hydrolysis by steric and electronic effects

Abstract: The various mechanisms by which a neighboring imidazolyl nitrogen base (both neutral and anionic) or the conjugate acid imidazolium cation may participate in the hydrolysis of an acetyl ester of a weakly basic or strongly basic phenol have been evaluated (pH 0-13). For this purpose 0-acetyl esters of 2 4 2 ’ and 4‘-hydroxypheny1)imidazoles were prepared (Ia, b, 11, IIIa, b, and IV). Lyate species access to the ester carbonyl carbon is quite similar for Ia, b, 11, and IV as shown by their nearly identical specific acid rate constants (k l , Table 111). For 11 the imidazole is para to the ester bond and therefore anchimeric assistance of hydrolysis is not possible. For esters IIIa and IIIb which possess bulky rert-butyl groups ortho to the ester bond, access by lyate species to the ester carbonyl group is greatly restricted as shown by the fact that the specific acid rate constant is -lo3 less than that determined for the other esters. At low pH (2-4) intramolecular participation by the o-imidazole function of esters Ia and Ib is evidenced by a plateau in the pH-log k o b s d profiles. Arguments presented favor general acid assistance to HzO attack by the neighboring imidazolium cation representing rate enhancements of 25and 150-fold for esters Ia and Ib, respectively. At neutrality a second plateau is observed for esters la, b, IIIa, and IV and is attributed to general base catalyzed H20 attack at the ester bond by neutral imidazole. The discussion correlates this mechanism with the like mechanism proposed elsewhere for the isomeric imidazolyl compound V and also for aspirin. Thus, a nearly 104-fold rate enhancement is seen over the uncatalyzed hydrolysis of Ia and similarly for Ib, IIIb, and IV. At alkaline pH (9-11) additional plateaus in the pH-log k o b s d profiles for esters Ib and IIIb are observed and present evidence for intramolecular acetyl group transfer to the imidazole anion with subsequent hydrolysis of the acetylimidazole intermediate. In the case of IIIb this intermediate is directly observable. Therefore the alkaline plateau regions and the ascending limbs of the pH-log k o b s d profiles in the most alkaline region represent rate-limiting specific base hydrolysis of acetylimidazole intermediates (AH and A, respectively of Scheme 11) derived from Ib and IIIb. The only pathway operable in the hydrolysis of IIIa in the pH range studied (811 5 ) is uia specific base attack on the corresponding acetylimidazole intermediate AH (Scheme 11). For esters Ia, 11, and IV (where IV cannot form an imidazole anion), specific base catalyzed hydrolysis of the ester bond is the preferred mechanism. Thus, depending upon the substituent groups on the phenyl acetate ring, three modes of intramolecular imidazole catalysis of ester hydrolysis can occur: (1) general acid assisted H20 attack, (2) general base assisted HzO attack, and (3) 0-N acetyl transfer to imidazole anion with subsequent hydrolysis of the intermediate acetylimidazole. All three modes of catalysis attain in the single ester Ib. The electronic and steric factors which mediate these different modes are discussed in detail. he implication of an imidazolyl group in the mechaT nism of catalysis by the serine esterases2 has led to extensive investigations of imidazole catalysis of ester hydrolysis. In intermolecular reactions involving phenyl acetates as substrates, bimolecular nucleophilic displacement of phenoxide (eq 1) is the exclusive pathway until the pK, of the conjugate acid of the leaving group exceeds that of imidazolium ion by (ApK,) Ei 3.0. When ApK, > 3 (with phenyl esters) general base assistance of the attack of imidazole by imidazole (eq 2) becomes of importance. When ApK, >> 3 (aliphatic esters), general base assistance of the attack of water by imidazole (eq 3) is the sole mechanism for catalysis of hydrolysis. In eq 1-3 the arrows are for bookkeeping purposes. The actual timing of proton transfer and covalent bond making and breaking processes is of much present concern.4 The changes of mechanism from eq 1 to 2 to 3 on increase in ApK, may be viewed as arising through the necessity of generating a nucleophilic species which is, in basicity, comparable to the leaving group.5 (1) A portion of the material submitted by G. A. Rogers in partial fulfillment of the requirements for the Ph.D. in Chemistry, University of Califorina at Santa Barbara. (2) T. C. Bruice and S. J. Benkovic, “Bioorganic Mechanisms,” Vol. I. W. A. Benjamin, New York, N. Y., 1966, Chapter 11. (3) (a) M. L. Bender and T. W. Turnquist, J. Amer. Chem. SOC., 79, 1956 (1957); (b) T. C. Bruice and G. L. Schmir, ibid., 79, 1663 (1957); (c) see Chapter 1 of ref 2 for a review. (4) W. P. Jencks, Chem. Reo., 72,705 (1972). The dependence of mechanism upon ApK, for intramolecular displacement reactions is amended by steric considerations. Thus, although acetate ion is incapable of displacing phenolate ion directly if ApK, > 2.6,6 in intramolecular reactions the COOgroup may directly displace alkoxide ions (ApK, 10) if a cyclic anhydride is formed and the alkoxide leaving group departs from the acyl product.’,* On the other hand, if the leaving group and COOmoiety are part of a single molecule, as in acetyl salicylate, direct nucleophilic displacement gives way to COOgeneral base catalyzed attack of H 2 0 when ApK, > 0.9 Though intramolecular imidazole catalysis of ester hydrolysis has received less attention than carboxylate intramolecular catalysis, the mechanistic requirements would seem to be similar. Thus, for phenyl esters of y-(4-imidazolyl) butyrate, direct nucleophilic displacement is a very facile process yielding the bicyclic lactam intermediate.l0.l1 For the acetyl ester,12 and presumably sub( 5 ) A tenet of the anthropomorphic rule: W. P. Jencks and J. E. Reimann, J . Amer. Chem. SOC., 88, 3973 (1966). (6) V. Gold, D. G. Oakenfull, and T. Riley, J . Amer. Chem. Soc., 90, 515 (1968). (7) J. W. Thanassi and T. C. Bruice, J . Amer. Chem. SOC., 88, 747 (1966). (8) If steric compression in the ground state is great, displacement may occur when ApK, S 12: A. J. Kirby, J. Chem. SOC., Chem. Commun., 834 (1972). (9) A. R. Fersht and A. J. Kirby, J. Amer. Chem. SOC., 90, 5818, 5826 (1968). Rogers, Bruice 1 Imidazole Catalysis of Ester Hydrolysis

Cytochrome P-450 difference spectra. Type II interactions in insecticide-resistant and -susceptible houseflies.

Abstract: The relationship between chemical structure and the difference spectra obtained with microsomes from the abdomens of insecticide-susceptible and -resistant houseflies was examined. The presence of a "sterically accessible" nitrogen atom with a pair of nonbonded electrons or an accessible oxygen atom in certain configurations appears to be of primary importance in the formation of type II difference spectra. However, factors such as steric hindrance and electronic configuration determine the spectral magnitude. The absorption maxima and minima vary with the ligand and the source of the cytochrome P-450. These data are discussed with reference to possible binding sites and to selectivity of ligands for them.