NMR analysis and site-specific protonation constants of streptomycin

Gábor Orgován, Béla Noszál

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)78-82
Number of pages5
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume59
Issue number1
DOIs
Publication statusPublished - Feb 5 2012

Keywords

  • Highly basic media
  • Microscopic acid-base properties
  • Microspeciation
  • NMR-pH titration
  • Streptomycin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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