Prediction of the chemiluminescent behavior of pharmaceuticals and pesticides.

The present paper deals with the first attempt to apply molecular connectivity calculations to predict a chemical property with analytical usefulness: the chemiluminescent behavior of substances when reacted with common oxidants in a liquid phase. Preliminary evidence when searching for new direct CL methods consisted of the examination of analyte reaction with a wide range of oxidants and media. This task, which results in time-consuming and trial-and-error expensive procedures, is necessary due to ensure empirical or theoretical rules for CL prediction are available. On the other hand, in quantitative structure-activity relationship studies, molecular connectivity is a topological method capable of describing the structure of a molecule by means of numbers named indices; subsequent regression in relation to the experimental values of the physical, chemical, or biological properties yields a series of functions called connectivity functions. Discriminant analysis was applied to 200 either chemiluminescent or nonchemiluminescent substances found either bibliographically or in an experimental screening. The method used for the selection of descriptors was a stepwise linear discriminant analysis from the Snedecor F-parameter. The classification criterion used was the minimum value of Mahalanobis. The quality of the discriminant function was calculated through the Wilks U-statistical parameter. Finally, the function was applied to a database including of more than 50,000 structurally heterogeneous compounds. The theoretical predictions were faced with the empirical evidence obtained through a continuous-flow manifold.

Correlation of pharmacological properties of a group of hypolipaemic drugs by molecular topology.

This investigation was undertaken to test the ability of the molecular connectivity model to predict the percentage of plasma protein binding, the percentage of total cholesterol reduction and oral LD50 in rats of a group of hypolipaemic drugs using multi-variable regression equations with multiple correlation coefficients, standard error of estimate, degrees of freedom, F-Snedecor function values, Mallow's CP and Student's t-test as criteria of fit. Regression analyses showed that the molecular connectivity model predicts these properties. Corresponding stability (cross validation) studies were made on the selected prediction models which confirmed their goodness of fit. The results also demonstrated that the presence of substituents and molecular volume, determine the value of these properties in hypolipaemic drugs.

Physico-chemical study of the radiopharmaceuticals 99mTc-DMSA, 99mTc-EDTA and 99mTc-DTPA interaction with plasmatic proteins.

This report studies the binding rate of the radiopharmaceuticals 99mTc-DTPA, 99mTc-EDTA and 99mTc-DMSA to plasmatic proteins. The proteins bind to the tested radiopharmaceuticals in the following sequence: 99mTc-DTPA less than 99mTc-DMSA(C1) less than 99mTc-EDTA less than 99mTc-DMSA(C2) where C1 and C2 represent two different Tc-DMSA complexes. The thermodynamic study suggests a quantitative relationship of radiopharmaceutical:protein = 1:1 and an almost nonexistent influence of the temperature, which means that the interacting forces in this process are relatively weak.

99mTc-tetracycline radiopharmaceutical: physical chemistry study related to the preparation and reaction products and thermodynamic stability.

The labelling of tetracycline hydrochloride with 99mTc at neutral pH, using Sn2+ as reducing agent, has been investigated by chromatography, using a 4:1:5 n-butanol:acetic acid:H2O mixture as developing agent, with Whatman paper No 3. In such conditions, reduced 99mTc remained at the origin, while labelled 99mTc migrates at Rf approximately equal to 0.6. Radiochromatographic and u.v.-visible spectrophotometric results, demonstrated that the higher the tetracycline concentration the higher was the labelling of 99mTc to that ligand, obtaining a 50% labelling when the molar ratio of tetracycline:Sn2+ was approximately 20:1, independent of the Tc concentration level. The Tc oxidation state in the radiopharmaceutical is +4, deduced from iodimetric and radiometric techniques. Furthermore, it seems that time does not influence labelling, while pH does. The maximum labelling level occurs at physiological pH. The thermodynamic study performed with the radiopharmaceutical formation shows that the Tc-tetracycline complex has a 1:1 stoichiometry, thus a low stability constant (about 2 X 10(2)).

[99mTc]Ca-phytate: some colloidal characteristics related to the optimal preparation conditions.

Some physico-chemical characteristics of the colloidal radiopharmaceutical [99mTc]Ca-phytate related to optimal preparation conditions have been studied. It is demonstrated that the Ca2+-phytate stoichiometry is 6:1. Two different Ca-phytate colloids seem to be formed, mainly depending on the Ca2+:phytate molar ratio--one of low mycelar size for a 1:1 Ca2+:phytate molar ratio (cmc = 5.10(-5) M), and another one, with a higher mycelar size for a 6:1 molar ratio (cmc = 8.10(-5) M). This last one it probably better for providing a good quality splenic uptake.

Stability of the radiopharmaceutical [99mTc]DMSA: study of the ligand exchange reaction with [99Tc]EDTA.

A kinetic study was made of the ligand exchange reaction between [99mTc]EDTA and DMSA. The results of this study indicate that this exchange reaction is closely related to temperature and pH. Kinetic and thermodynamic parameters demonstrate that both complexes--[99MTc]EDTA and [99mTc]DMSA--have a similar stability. Furthermore, the existence of an acid-basic catalysis for the global exchange reaction was established, and the catalytic parameters were calculated. These data were obtained by radiochromatography and visible spectrophotometry.