Metal ion-tetracycline interactions in biological fluids. Part 8. Potentiometric and spectroscopic studies on the formation of Ca(II) and Mg(II) complexes with 4-dedimethylamino-tetracycline and 6-desoxy-6-demethyl-tetracycline.

摘要: Effects of metal ion-tetracycline (TC) interactions on both gastrointestinal absorption and pharmacological activity these drugs are well documented. In particular, recent simulation studies based newly determined complex stability constants have drawn attention to the potential influence Ca2+ Mg2+ ions bioavailability various TC derivatives in blood plasma. Contrary previous thoughts, it was demonstrated that fraction antibiotic not bound proteins almost exclusively occurs as calcium magnesium complexes. Among this fraction, predominant binuclear species electrically charged, such cannot passively diffuse through cell membranes. It thus postulated partial blocking one coordination sites molecule, which would favor formation neutral mononuclear complexes, should result a better tissue penetration drug. Such correlations were recently established for specific derivatives. Before possible modifications molecule can be envisaged, is necessary all chelating involved relevant complexes properly assigned. As tetracyclines very ligands, present paper first deals with two simpler parent substances, i.e., 4-dedimethylamino-tetracycline (DTC) 6-desoxy-6-demethyl-tetracycline (DSC). After quantitative investigation proton equilibria involved, UV circular dichroism spectroscopies used study corresponding structural aspects. DTC BCD ring system acts exclusive site metals. For DSC, however, N4 atom plays leading role binding only donor 1:1 species; ML2 second ligand thought bind system.