R. Garcia Domenech

Prediction and Interpretation of Some Pharmacological Properties of Cephalosporins Using Molecular Connectivity

SummaryA method of molecular connectivity was used to study the pharmacological and antimicrobial properties of 34 cephalosporin antibiotics to verify its applicability to these parameters.By using Kier and Hall connectivity indices (Xi) as well as geometric indices (GIs), good correlation equations were obtained with a low number of variables. In some cases, such as the lethal dose for 50% of group (LD50) values and minimum inhibitory concentration (MIC) values for Pseudomonas aeruginosa, better regression equations were obtained with the GIs alone, confirming their alternative nature with respect to Xi, indices.

Molecular topology and chromatographic retention parameters for benzodiazepines

Abstract The relationship between gas-liquid chromatographic (GLC) retention properties and R F values in thin-layer chromatography (TLC) with molecular connectivity indices, m X t , was investigated for a series of benzodiazepines using multiple correlation coefficients, standard errors of estimate, F -Snedecor function values and Students t -test as the criteria for best equation selection. Regression analyses show that the molecular connectivity model predicts the retention properties in GLC with the polar stationary phase OV-17 at 280°C and the R F values in TLC with the stationary phase silica gel. However, zero- or second-order connectivity indices alone are not sufficient; higher-order indices are shown to be necessary. The effect of the polarity of the mobile phases in TLC was also investigated.

Event-based criteria in GT-STAF information indices: theory, exploratory diversity analysis and QSPR applications

Versatile event-based approaches for the definition of novel information theory-based indices (IFIs) are presented. An event in this context is the criterion followed in the “discovery” of molecular substructures, which in turn serve as basis for the construction of the generalized incidence and relations frequency matrices, Q and F, respectively. From the resultant F, Shannons, mutual, conditional and joint entropy-based IFIs are computed. In previous reports, an event named connected subgraphs was presented. The present study is an extension of this notion, in which we introduce other events, namely: terminal paths, vertex path incidence, quantum subgraphs, walks of length k, Sachs subgraphs, MACCs, E-state and substructure fingerprints and, finally, Ghose and Crippen atom-types for hydrophobicity and refractivity. Moreover, we define magnitude-based IFIs, introducing the use of the magnitude criterion in the definition of mutual, conditional and joint entropy-based IFIs. We also discuss the use of information-theoretic parameters as a measure of the dissimilarity of codified structural information of molecules. Finally, a comparison of the statistics for QSPR models obtained with the proposed IFIs and DRAGONs molecular descriptors for two physicochemical properties log P and log K of 34 derivatives of 2-furylethylenes demonstrates similar to better predictive ability than the latter.

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

Abstract This report studies the binding rate of the radiopharmaceuticals 99m Tc-DTPA, 99m Tc-EDTA and 99m Tc-DMSA to plasmatic proteins. The proteins bind to the tested radiopharmaceuticals in the following sequence: 99m Tc-DTPA 99m Tc-DMSA(C 1 ) 99m Tc-EDTA 99m Tc-DMSA(C 2 ) where C 1 and C 2 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]Ca-Phytate: Some colloidal characteristics related to the optimal preparation conditions

Abstract Some physico-chemical characteristics of the colloidal radiopharmaceutical [ 99 m Tc]Ca-phytate related to optimal preparation conditions have been studied. (1,2) It is demonstrated that the Ca 2+ -phytate stoichiometry is 6:1. Two different Ca-phytate colloids seem to be formed, mainly depending on the Ca 2+ :phytate molar ratio-one of low mycelar size for a 1:1 Ca 2+ :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

Abstract A kinetic study was made of the ligand exchange reaction between [ 99 m Tc]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—[ 99 m Tc]EDTA and [ 99 m Tc]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.

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

Abstract 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 R f ⋍ 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 × 102).