Multinuclear Nuclear Magnetic Resonance Spectroscopy Is Used to Determine Rapidly and Accurately the Individual p KaValues of 2-Deoxystreptamine, Neamine, Neomycin, Paromomycin, and Streptomycin

Abstract

Unambiguous assignments have been made for each individual pKa value of the amino group and guanidine substituents on 2-deoxystreptamine, neamine, neomycin, paromomycin, and streptomycin by pH-titration evaluation of their 1H, 13C, and 15N (by 1H-15N heteronuclear multiple-bond correlation (HMBC) spectra) NMR chemical shifts (δXs) as the reporter nuclei. These data require minor revisions of the literature data in terms of the assignment order for neomycin and paromomycin. In situ titrations and NMR spectroscopy are shown to be a powerful combination for rapidly (minutes) obtaining each distinct pKa value of the similar amine and guanidine functional groups, which decorate aminoglycoside antibiotics.