F. García Blanco

Analysis of the solvent effect on the photophysics properties of 6-propionyl-2-(dimethylamino)naphthalene (PRODAN).

The absorption and emission spectroscopic properties of 6-propionyl-2-(dimethylamino)naphthalene (PRODAN) have been studied in a large number of protogenic, nonprotogenic, and amphiprotic solvents. The data obtained can be explained by the inclussion of a new term in the Lippert equation which takes into account the acidity of the solvent. This finding indicates that some precaution should be taken when using PRODAN as an indicator of the polarity of protein cavities if the environments involved include acid sites.

Theoretical calculations of β-lactam antibiotics: Part 2. AM1, MNDO and MINDO/3 calculations of some cephalosporins

Abstract The geometries of several cephalosporins were determined by the MINDO/3, MNDO and AM1 semiempirical calculation methods. The geometric parameters of the bicyclic system thus obtained (bond distances and angles, and dihedral angles ) were compared with crystallographic and literature data. Of the three methods used, MINDO/3 provided the best estimations of the geometric values, while MNDO reproduced the pyramidal character of the β-lactam nitrogen with the greatest accuracy and AM1 yielded an intermediate solution. All three methods were used to carry out a comprehensive conformational analysis of the bicyclic system. In this respect, MINDO/3 only detected one minimum, while both MNDO and AM1 yielded two minima, corresponding to two extreme situations (S1-up and C2-up).

Theoretical calculations ofβ-lactam antibiotics: Part 1. AM1, MNDO and MINDO/3 calculations of some penicillins

Abstract MINDO/3, MNDO and AM1 calculations have been carried out in order to calculate the geometry of some penicillins. Theoretical bond lengths, bond angles and dihedral angles have been checked with crystallographic data. Results show that MINDO/3 is the best method for predicting the geometry of the bicyclic system. However, it is not very good in predicting the conformations and pyramidality of the β-lactam nitrogen. In spite of its poor accuracy in predicting the geometry of the antibiotic, the MNDO method reproduces very well the pyramidality of the β-lactam nitrogen. The AM1 method predicts the geometry of the system quite well, except for the S-C and C7-N4 bond lengths which are underestimated and overestimated respectively. In addition, AM1 is very good at treating conformations of the thiazolidine ring.

Theoretical calculations of b-lactam antibiotics. V: AM1 calculations of hydrolysis of cephalothin in gaseous phase and influence of the solvent

A comprehensive study on the gas‐phase alkaline hydrolysis of cephalosporins by using the semiempirical AM1 method was carried out. Cephalothin was the model compound used on account of the presence of a good leaving group at C(3′). According to the results obtained, the hydrolysis process takes place via a twostep reaction mechanism that involves the formation of an intermediate with a fully open β‐lactam ring that still preserves the acetate group. Likewise, the exo methylene end product is chiefly formed by nucleophilic attack on the β‐lactam carbonyl group of cephalosporins containing a good leaving group at C(3′). On the other hand, the alternative mechanism involving hydrolysis of the ester function in the side chain at 3′ and subsequent hydrolysis of the resulting β‐lactam yieds essentially the corresponding enamine. The presence of a first solvation layer consisting of five water molecules showed that, even though some potential barriers are slightly increased, the mechanism involved is identical to that of the gas‐phase hydrolysis of this antibiotic.

Semiempirical and ab initio calculations on the alkaline hydrolysis of the β-lactam ring Influence of the solvent

We used semiempirical and ab initio calculations to investigate the nucleophilic attack of the hydroxyl ion on the fl-lactam carbonyl group. Both allowed us to detect reaction intermediates pertaining to proton-transfer reactions. We also used ab initio calculations and the PM3 semiempirical method to investigate the influence of the solvent on the process. The Ah4SOL method predicts the occurrence of a potential energy barrier of 20.7 kcal mol-’ due to the desolvation of the hydroxyl ion in approaching the p-lactam carbonyl group. Using the supermolecular approach and a water solvation sphere of 20 molecules around the solute, the potential energy barrier is lowered to 17.5 kcal mol-‘. Ab initio calculations using the SCRF method predict a potential energy barrier of 13.6 kcal mol-’ . These three values, especially the last two, are very close to the experimental value of 16.7 kcal mol-‘.

Intrinsic viscosity calculated out of single point measurements for chondroitin-4-sulfate and chondroitin-6-sulfate solutions

The differences in the structure of polymer chain between the chondroitin-4-sulfate (C4-S) and the chondroitin-6-sulfate (C6-S) are reflected in the intrinsic viscosity values calculated starting from the traditional methods of Huggins, Kraemer, Mead and Fouss, and Martin, and by the method for a single-point determination of intrinsic viscosity [eta]. For the range between 0.4 and 0.5% (w/v) concentrations, we get an agreement in the intrinsic viscosity values. The chains of both polymers present a flexible structure and are not ramified between 0.28 and 1.00% (w/v) concentrations.

Alkaline hydrolysis of N-methylazetidin-2-one. Hydration effects

Abstract Semiempirical calculations (PM3) have been used to investigate the reaction mechanism (BAC2) of the alkaline hydrolysis of N-methylazetidin-2-one. This mechanism involves the nucleophilic attack of a hydroxyl ion on the carbonyl carbon to give a tetrahedral complex followed by cleavage of the CN bond and proton transfer to form the final product. The influence of the solvent in this process has been analyzed using the supermolecular approach with a water solvation sphere of 20 molecules around the solute. The results obtained have been compared with those based on a continuum treatment of the solvent with semiempirical and ab initio methodology. The potential barrier of 17.5 kcal mol−1 due to the attack of the nucleophile is very close to the experimental value (16.1 kcal mol−1) and the final product is about 52 and 27 kcal mol−1 more stable than the reactives and the tetrahedral intermediate, respectively.

Stability of Schiff bases of amino acids and pyridoxal-5′-phosphate

SummaryStability of Schiff bases from Pyridoxal-5′-phosphate andα- and nonα-amino acids and amines have been studied in a wide range of pH. Furthermore the transamination process for the PLP-serine Schiff base and the cyclization reaction of PLP-histidine Schiff base have also been studied.Results show that theα-position on carboxyl group of amino acids plays an important role on the mechanism of hydrolysis of imine bond. Absence of ionic groups in the surroundings of that bond seems to be an important fact of stability.In the transamination reaction, the rate-determining step is the isomerization of the Schiff base to ketoimine, since the rate constants for disappearance of Schiff base coincide with the rate constants for PMP formation. This process is catalyzed by the OH−/H2O system and the monoprotonated amino acid.

Semiempirical calculations of the hydrolysis of penicillin G

Abstract A theoretical study of the gas-phase alkaline hydrolysis of penicillin G on the assumption of a B AC2 mechanism is reported. Various semiempirical methods were used to determine the influence of different parameterizations on the process. Among the most salient results obtained, the standard AM1 method predicted opening of the thiazolidine ring to yield the corresponding imine and enamine structures.

Amino acid catalytic effect on the transamination reaction between pyridoxal 5′-phosphate and L-serine

Abstract The kinetic study of Schiff base formation between pyridoxal 5′-phosphate (PLP) and L-serine and its subsequent transamination to yield pyridoxamine 5′-phosphate (PMP) and ketoacidate ion has been carried out over a wide pH range by fluorescence and UV—Vis measurements. The kinetic constants of Schiff base formation are compared with constants of other PLP—amino acid systems, showing the existence of an intramolecular general acid catalysis of PLP and general basic catalysis of the amino acid. The rate-determining step of the schiff base transamination is the isomerization of this compound to ketoimine, since the rate constants for disappearance of Schiff base coincide with the rate constants for PMP formation. This process is catalyzed by the OH−/H2O system and the monoprotonated amino acid.