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D B Boyd

Publications and source records attributed to D B Boyd.

At least 37 records · Page 2Linked to original sources
PubMed1986

Examination of model enzyme and penetration systems in relation to antibacterial activity.

Recent work has shown that the activity of cephalosporins in inhibiting exocellular DD-peptidases from Streptomyces R61 and Actinomadura R39 are, at best, only poorly related to minimum inhibitory concentrations against pathogenic isolates. Taking into account the rate at which cephalosporins diffuse through porin channels, such as exist in certain Gram-negative organisms, does not help in establishing a relationship between MIC data and the kinetic data on the model enzymes. Most published cell wall permeability studies, the porin ones being a principal exception, have not examined long enough series of structurally related compounds to establish property-activity relationships.

Acyltransferases↗
PubMed1984

Electronic structures of cephalosporins and penicillins. 15. Inductive effect of the 3-position side chain in cephalosporins.

Induction appears to be the primary means by which the side chain at position 3 of the cephem nucleus influences the chemical reactivity of the beta-lactam ring. In vitro antibacterial activity data suggest that when the cephalosporin is in the active site of the target bacterial enzymes, the presence of a leaving group in the side chain can promote inhibition.

Cephalosporins↗
PubMed1984

Correlations between CNDO/2 charge distribution and 13C NMR chemical shift in 7-acylamino side chains of cephalosporins.

Molecular orbital calculations by the CNDO/2D method yield charge distributions which correlate well with the observed 13C NMR chemical shift for the amide carbon of acylamino side chains of cephalosporins. Acyl groups that withdraw electrons from the amide C-N bond and concomitantly make the amide nitrogen more negatively charged increase the chemical shift. The trends are related to the degree of amide resonance. No direct correlation was found between the chemical shift of the amide carbon and the antibacterial activity of the cephalosporins.

Carbon Isotopes↗
PubMed1984

Conformational flexibility of the methyltetrazolethiomethyl side chain of beta-lactam antibiotics. A computer graphics study.

Analysis of X-ray crystallographic data for cephalosporins and 1- oxacephalosporins shows that, although the 1-methyl-1H- tetrazol -5- ylthiomethyl side chain at position 3 of a bicyclic beta-lactam nucleus has certain conformational preferences, it also has considerable flexibility. Both the C4 = C3-C3'-S and C3-C3'-S-C5" torsional angles are frequently observed in the vicinity of +/- 90 degrees. The distance between the tetrazole ring carbon C5" and the 4-carboxyl carbon ranges from 4.07 to 5.65 A. Mean bond lengths and bond angles for the 3 and 4 side chains are tabulated.

Anti-Bacterial Agents↗
PubMed1983

Substituent effects in cephalosporins as assessed by molecular orbital calculations, nuclear magnetic resonance, and kinetics.

For cephalosporins with different side chains at position 3, the quantum mechanically computed charge distribution in the beta-lactam carbonyl group can be correlated with observables, such as carbon-13 chemical-shift differences at C3 and C4 of the dihydrothiazine ring and alkaline rates of hydrolysis of the beta-lactam. The relationship of these properties and the theoretical transition-state energy (TSE) corroborate the fact that chemical reactivity is one important determinant affecting inhibitory activity of cephalosporins against peptidoglycan-regulating enzymes.

Cephalosporins↗
PubMed1979

Conformational analogy between beta-lactam antibiotics and tetrahedral transition states of a dipeptide.

The three-dimensional structures of various penicillins and cephalosporins are compared to the spatial characteristics of glycylglycine and the tetrahedral adducts formed when a nucleophile attaches to the amide carbonyl carbon of this dipeptide. The dipeptide is taken to model the D-alanyl-D-alanine terminus of the precursors of bacterial cell-wall peptidoglycan cross-links. Least-squares fitting shows that the spatial match between the dipeptide and the antibiotic depends on the thiazolidine or dihydrothiazine ring conformation, as well as the conformation of the dipeptide. In general, the tetrahedral adducts fit somewhat better than the parent dipeptide. A previously unobserved 3-cephem conformer is found by molecular mechanics calculations to be less stable than the usual crystallographically observed conformer.

Cephalosporins↗
PubMed1979

Electronic structures of cephalosporins and penicillins. 9. Departure of a leaving group in cephalosporins.

Molecular orbital calculations by the CNDO/2 method are used to study the potential energy surface for the stretching and rupturing of the CH2-OAc bond in a model cephalosporin structure, 7-amino-3-(acetoxymethyl)-3-cephem. The bond is easier to stretch and break when a nucleophilic group is in the vicinity of or attached to the beta-lactam carbonyl carbon (C8). The rate of acylation by a beta-lactam antibiotic at the receptor sites in bacterial cell-wall enzymes will be enhanced by a suitable leaving group at the 3' position. An orientational specificity is predicted for the direction of departure of the leaving group. Regardless of the direction the nucleophile approaches C8, the CH2-OAc bond is easiest to break when the acetate group departs from the alpha face of the molecule.

Cephalosporins↗
PubMed1978

A note on the description of pain and its causes.

The adjectives used by 72 psychiatric patients to describe pain were examined. Patients with physical lesions tended to have physical precipitants and physical relieving factors. Patients with psychologically based pain often recognized both physical and emotional preciptation. Most adjectives used were sensory rather than affective or evaluative.

Female↗
PubMed1977

Transition state structures of a dipeptide related to the mode of action of beta-lactam antibiotics.

The tetrahedral adducts formed during nucleophilic attack by a hydroxyl ion on the carbonyl carbon of a model dipeptide, glycylglycine, were studied by modified-intermediate-neglect-of-differential-overlap molecular orbital calculations. This dipeptide is taken to represent the D-alanyl-D-alanine terminus of the polypeptides involved in the cross-linking transpeptidation reaction of peptidoglycan in bacterial cell walls. It was found that nucleophilic attack on one face of the carbonyl carbon leads to a transition intermediate species structurally similar to that afforded by the bicyclic nucleus of penicillins and cephalosporin antibiotics. The results support the concept that the beta-lactam antibiotics, which are known to inhibit various bacterial cell wall enzymes, may act as transition state analogs. Also, the structure formed from nucleophilic attack on the so-called alpha face of the dipeptide is more similar to the antibiotic structures than is that from attack on the opposite face. In agreement with other types of experiments, the results suggest that the alpha face may be the one approached by a nucleophile in the receptor site(s) of the appropriate cell wall enzymes.

Cephalosporins↗
PubMed1975

Electronic structures of cephalosporins and penicillins. 4. Modeling acylation by the beta-lactam ring.

Molecular orbital calculations by the CNDO/2 method are used to study the molecular and electronic details involved in the initial phases of the opening of the beta-lactam ring of a model cephalosporin structure, 7-amino-3-acetoxymethyl-3-cephem. The effect of a simple nucleophile, OH-, approaching the carbonyl carbon center of the beta-lactam ring is monitored by following the charge redistributions that occur in the bicyclic system and in the 3 side chain. A migration of electron density to the ester oxygen of the CH2OAc group is observed with concomitant weakening of the CH2-OAc bond. The results are discussed in relation to the mechanism of acylation of bacterial cell wall enzymes by beta-lactam antibiotics and in relation to the hydrolysis of these molecules. The results indicate that the ability of the 3' substituent of cephalosporins to stabilize electron density transferred to it, i.e., the leavability of the 3' moiety, can be an important factor in activating the beta-lactam toward nucleophilic attack.

Acylation↗