title: NMR analysis and site-specific protonation constants of streptomycin.
abstract: Streptomycin, the classical aminoglycoside antibiotic, generally considered the most basic drug compound was characterized in terms of protonation macro- and microconstants. ¹H NMR-pH and ¹H-¹³C HSQC-pH titrations were carried out on streptomycin and streptidine, a symmetrical constituent compound of reduced complexity to monitor the proton-binding processes of the basic sites. Accurate, undistorted, electrodeless pH measurement was ensured by a new set of in tube indicators. The microscopic protonation constants of the two guanidino groups of streptomycin were calculated by evaluating the various NMR-pH data and transferring the pair-interactivity parameter from streptidine to streptomycin. Inherent guanidino basicities fall in the range of 13.03-13.39 log k units, which drop to 12.48-12.85 upon protonation of the other site. pH-dependent distribution of the major microspecies and charge-related biological consequences are provided.
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Research Group of Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Budapest H-1092, Hőgyes Endre U. 9, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Orgován
authors.forename: Béla
authors.initials: B
authors.lastname: Noszál
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000737:chemistry; D006146:Guanidines / Q000032:analysis* / Q000737:chemistry; D006595:Hexosamines / Q000032:analysis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D011522:Protons; D013307:Streptomycin / Q000032:analysis* / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D006146:Guanidines; D006595:Hexosamines; D011522:Protons; C005733:streptidine; D013307:Streptomycin