Streptomycin Hydrazone Derivatives: Synthesis and Molecular Recognition in Aqueous Solution

Abstract

Five hydrazone derivatives of streptomycin were synthetized (D0h, D1ph, D2bt, D3dctf, D4ag) and characterized by IR, ¹H and ¹³C NMR spectroscopy, mass spectrometry and elemental analysis. Protonation constants were determined by potentiometry for all derivatives. D1ph and D2bt derivatives were investigated as receptors of dicarboxylates and adenine nucleotides in aqueous solution by potentiometric and ¹H NMR titrations. D1ph and D2bt derivatives have the highest affinity with AMP and ATP, respectively, which shows that electrostatic forces are not always the dominant factor in binding of streptomycin derivatives with nucleotides, but the conformational fit between them. Calculated structures at the DFT level of the D1ph derivative bonded with either AMP or ADP showed that the complexes are stabilized by the formation of multiple interactions with the receptors. The antibiotic activity of the derivatives was explored and compared with native streptomycin.