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

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 amongst 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 (API). Furthermore, substitution of inactive gluconate with bioactive cyclamate counterion potentially provides the additional benefit of improving the taste profile of chlorhexidine.