Synthesis, Characterization, and Antimicrobial Investigation of a Novel Chlorhexidine Cyclamate Complex

Abstract

The synthesis, crystal structure, and antimicrobial efficacy are reported for a novel material comprising a 1:2 ratio of chlorhexidine (CHX) to N-cyclohexylsulfamate (i.e., artificial sweetener known as cyclamate). The chemical structure is unambiguously identified by incorporating a combination of single-crystal X-ray diffraction (SC-XRD), electrospray ionization mass spectrometry (ESI-MS), 1H nuclear magnetic resonance (NMR) spectroscopy, correlation spectroscopy (COSY), and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR). The new material: (1) is among only several reported structures identified to date incorporating the vital chlorhexidine antimicrobial drug; (2) exhibits broad spectrum antimicrobial activity at concentrations less than 15 μg/mL; and (3) provides a unique delivery method for the essential active pharmaceutical ingredient. Furthermore, substitution of inactive gluconate with bioactive cyclamate counterion potentially provides the additional benefit of improving the taste profile of chlorhexidine.