L. Benedetti

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.

A theoretical and topological study on the electroreduction of chlorobenzene derivatives

The electrochemical behaviour of 12 polychlorobenzene derivatives is discussed on the basis of calculated quantum-mechanical indexes (CNDO/2, MNDO, AM1 methods) and of pure structural parameters reckoned by means of graph theory (Wierner, Balaban, Randic, PID and Wrms numbers). Even the existence of good relationships between reduction potentials and energies of virtual molecular orbitals, π* or σ*(closed-shell calculations), does not account for the details of the electron uptake at the molecular level. Open-shell calculations (MNDO) regarding unrelaxed radical anions are much more promising in this respect, the occurrence of the so-called ‘ortho effect’ can be so justified. The reductive process (at least in the experimental conditions considered here) is shown to be scarcely affected by solvent-shell or internal molecular rearrangements; this view is supported by the good description of the process, strictly on structural grounds regarding the whole of the molecule, provided by the graph-theoretical indexes.

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.

Electrosorption of ‘hard’ and ‘soft’ aromatic derivatives on mercury

An ‘intrinsic’ value of the adsorption Gibbs energy (ΔG°int)∥, not directly proportional to the measured ΔG∥ads, has been evaluated for a set of 28 aromatic, heterocyclic and naphthalenic derivatives. The structural feature of (ΔG°int)∥ is rationalised in terms of a ‘soft’ interaction with mercury at the point of zero charge, on the basis of the parr and Pearson concept, accounting on a quantitative basis for the different adsorbability of the compounds. Moreover, the partial charge-transfer coefficient, λ, has been related in a satisfactory way to ΔN(the fractional number of electrons transferred) calculated taking into account the absolute electronegativitiy, χ, and the hardness, η, both of the adsorbate and of mercury.

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.

Phase transition in the adsorption process of N-dansylglycinate anion on mercury

The adsorption of N-dansylglycine in its monoanionic and dianionic molecular forms has been characterized in aqueous solution (1 M NaClO 4 as base electrolyte) at the mercury electrode, for concentration values lower than 7 mM

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.