G. Grandi

Half-wave potential of sulfa drugs as structural index

Abstract The polarographic study of 21 N1-substituted sulfa drugs has shown that the overall reduction process on an Hg electrode depends on the protonicity of the solvent and on the number of substituents on the N1 nitrogen (mono- or disubstituted). However, these features do not appear to influence the E1/2 values as they maintain a strict correlation in aprotic (DMF) vs. protic medium (C2H5OH), regardless of the number of substituents on amidic nitrogen. It has also been shown that the N1-substituents cause large shifts of the half-wave potential, so ΔE1/2 can be used as a kind of “substituent constant”. Correlations with pKa and spectroscopic data, as well as with the antibacterial potency of these compounds, have been obtained and discussed.

Complex formation of zinc(II) ion with glycine, N-acetyl- and N-benzoyl-glycine anions in aqueous and ethanolic solution by polarographic method

The complex formation reactions of glycine, N-acetyl- and N-benzoyl-glycine with the Zn(II) ion were investigated using the polarographic method in aqueous and ethanolic solution to identify the number and type of complex species present in solution and to calculate their stability constants. In aqueous basic solution (pH 6–9), only the glycinate anion reacts with the metal ion forming three complexes of the type ZnL+, ZnL2 and ZnL−3. On the contrary in ethanolic solution all three amino acids react; the N-protected amino acid anions form four complexes of the type ZnL+, ZnL2, ZnL−3 and ZnL2−4, while in the presence of the glycine anion two complexes only of the type ZnL+ and ZnL2 were identified. The results obtained for these systems in aqueous and ethanolic solution, discussed in comparison with those of the corresponding cadmium(II) systems, also suggest an amino acid coordination to the metal ion through different coordination sites in the solvents examined.

The effect of a dansyl group on the co-ordinative ability of N-protected amino acids. Part 1. Behaviour of the copper(II) ion–N-dansylglycinate system in aqueous and methanolic solution

Polarographic, potentiometric, and spectrophotometric measurements show that copper(II) and N-dansylglycine (5-dimethylaminonaphthalene-1-sulphonylglycine) form the same complexes in aqueous and methanolic solution. Mixed-hydroxy complexes are the prevailing species. In aqueous (methanolic) solution up to pH 5(5) no formation of complexes is observed; in the pH range 7–8.5 (8.5–11) a change in the ligand co-ordination from O-co-ordination through the carboxylate group to N,O-bidentate co-ordination through the carboxylate oxygen and the deprotonated amide nitrogen is revealed. There is a low tendency for two N-dansylglycine ligand molecules to coordinate to the CuII ion, probably due to the steric hindrance of the dansyl group. The equilibria in which the prevailing complexes are involved and the reduction processes at the electrode are proposed. The nucleophilic and electrophilic properties of the two solvents are used to explain the solvent effect on the polarographic parameters and on the stability constants of the complexes.

Physico-chemical behaviour of sulpha drugs: VI. Electrochemical behaviour and electronic structure of sulphonamide derivatives

Abstract The electrochemical reduction of OSO2NH2 and its ortho, para and meta amino derivatives was examined in aprotic medium (CH3CN) with varying experimental conditions, i.e. drop time, concentration and temperature. It has been shown that the reduction process is irreversible and controlled by diffusion at small values of concentration and low drop times, while the whole process is controlled by an adsorption step at larger values of concentration and drop times. The reduction mechanism, proposed by Horner for sulphonamides of the type XOSO2NR1R2, was confirmed and shown always to involve the S-N bond cleavage. Half-wave potentials and electrokinetic parameters were correlated with some theoretical and experimental structural indexes. Even if the correlation is fairly good and confirms the validity of the theoretical model assumed, it does not enable the pharmacological behaviour of the three isomers to be differentiated.

Electrochemical reduction of N-substituted benzenesulphonamides and their p-amino derivatives in several solvents

Abstract The polarographic study of a series of N-substituted benzenesulphonamides and their p-amino derivatives, in aprotic and protic media (CH3CN, dimethylformamide, C2H5OH), has shown that the electrochemical reduction of these compounds involves the S−N bond cleavage and follows the mechanism proposed by Cottrell and Mann. It has also been shown that the effect of the substituents on the amidic nitrogen on the half-wave potential is independent of the protonicity of the solvent used, so the E1/2 value can be regarded as a good structural index. From the polarographic data, a series of polar inductive substituent constants is obtained, the validity of which has been proved also by comparison with other experimental physicochemical parameters of these compounds related to their molecular structure.

Comparison of the polographic behavior of the Cd2+-glycine, N-acetyl- and N-benzoyl-glycine systems in aqueous and ethanolic solution

Abstract The complexation reactions of glycine, N-acetyl- and N-benzoyl-glycine with the Cd2+ ion were studied as a model for metal-protein interactions, using polarographic techniques in aqueous and ethanolic solution at 0.1 M NaclO4, as base electrolyte, to identify the number and type of solution complex species and to calculate their stability constants. In aqueous solution three complexes of the forms CdL+, CdL2 and CdL-3 coexist in the pH range 7–10 for the glycine, while the N-protected amino acids do not react under any pH conditions. In ethanolic solution four complexes of the forms CdL+, CdL2, CdL-3 and CdL2-4 coexist for the N-protected amino acids, while for the glycine the CdL2-4 complex prevails. A Hammett relationship is observed between the reversible E 1 2 of β4 (stability constant)values versus the σ constants for the substituents on the amino group. A coordinative hypothesis for the complexes in solution is also suggested.

Adsorption of benzoic acid, N1-phenyl and N1-2-pyrimidinyl benzenesulfonamide derivatives at the mercury-aqueous solution interface

Abstract Adsorptions of ΦCOOH, ΦSO 2 NHΦ and ΦSO 2 NH pyrimidine were studied by a differential capacitance method at pH=12 at the dropping mercury electrode. The interfacial behaviour of each compound was compared with that of the corresponding p -amino derivative: The experimental γ max values are approximately the same, while the experimental −Δ G ads o , at constant potential, are lower by a constant contribution. Moreover, the two oxygen atoms still seem to be directly involved in the adsorption process. Finally, the relevance of the p -NH 2 substitution on the pharmacological properties of these compounds is discussed.

Interfacial behaviour of N1-substituted sulfanilamides at the mercury-solution interface: Adsorption of N1-2-pyrimidinyl and N1-2(4,6-dimethyl) pyrimidinyl derivatives and structural parameters

The adsorption of two N1-sulfanilamide derivatives, N1-2-pyrimidinyl and N1-2(4,6-dimethyl)pyrimidinyl, was studied by a differential capacitance method at pH=12 at the dropping mercury electrode. The area occupied by each molecule of these compounds, adsorbed at the mercury-electrolyte solution interface, corresponds well to the area expected for a molecule adsorbed flat on the electrode with its pNH2O-S moiety. This is confirmed by the correlation between the adsorption free energy (at constant potential) and the polarographic “substituent constant” which reflects the effect of N1-substitution on the electronic structure on the pNH2O-S moiety. Finally, the good linear correlation between ΔGads0 values and the activity parameters related to the biological activity of sulfanilamides suggests the presence of an adsorption step in the mechanism of action able to account for the different bacteriostatic potencies of the compounds.

Effect of the solvent properties on the polarographic behaviour of the Zn2+ and Cd2+ complexes with glycine, N-acetyl and N-Benzoyl glycine

Abstract The polarographic behaviour of Zn2+ and CD2+ and their complexes with glycine, N-acetyl and N-benzoylglycine has been studied in DMSO, CH3CN and DMF; the results have been compared with those previously obtained in H2O and C2H5OH. The effect of the solvent properties on the reduction of those systems has been explained in terms of the electron pair donor (EPD) and of electron pair acceptor (EPA) strength of the solvent itself. The higher the donor number (DN), the more negative the E 1 2 value both of the free metal ions and the complexes. Moreover, the stability constants of the complexes, polarographically determined, seem to be related to the acceptor number (AN) of the solvent.

Electrochemical behaviour of chlorobenzenesulphonamide derivatives at the mercury electrode in non-aqueous solvents

Abstract The analysis of polarographic and coulometric results shows that the overall reduction mechanism of chlorobenzenesulphonamide derivatives occurs with the cleavage of the CCl bond followed by the reduction of the benzenesulphonamide involving the SN bond breaking. However, the E sol1 2 values fit the structural relation E 1 2 -ELUMO for the series of benzenesulphonamides and not that of the cholorobenzene derivatives and the shape of the LUMO of cholorobenzenesulphonamides is similar to that of the benzenesulphonamide, so that it is sensible to suggest that the first step of the reduction mechanism is the same for all the benzenesulphonamide derivatives and involves the CSN moiety of the molecules.