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),
1
H 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.
The facile synthesis of chlorhexidine dicyclamate yields a material with applications as a broad spectrum antimicrobial agent. The minimum inhibitory concentrations (MICs) of the newly discovered material is comparable to chlorhexidine digluconate for Streptococcus mutans while slightly reducing the overall amount of the drug since cyclamate exhibits a smaller molecular weight than gluconate. Additionally, the substitution of the biologically inert gluconate anion with the bioactive artificial sweetener cyclamate (
i.e.
, N-cyclohexylsulfamate,) counterpart yields a material which can potentially enhance the taste profile.