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Download fileIntercalation of Benzoxaborolate Anions in Layered Double Hydroxides: Toward Hybrid Formulations for Benzoxaborole Drugs
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posted on 2015-02-24, 00:00 authored by Saad Sene, Sylvie Bégu, Christel Gervais, Guillaume Renaudin, Adel Mesbah, Mark E. Smith, P. Hubert Mutin, Arie van der Lee, Jean-Marie Nedelec, Christian Bonhomme, Danielle LaurencinBenzoxaboroles are a family of cyclic
derivatives of boronic acids,
whose reactivity makes them interesting candidates for the development
of novel drugs. In this study, we describe the preparation of the
first hybrid organic–inorganic materials involving benzoxaboroles,
as a first step toward their use as new formulations for such drugs.
The materials were prepared by intercalation of the simplest benzoxaborole
(C7H6BO(OH), BBzx) or of its fluorinated analogue
(C7H5FBO(OH), AN2690, a recently developed antifungal
drug), both taken under their anionic form (benzoxaborolate), into
a biodegradable inorganic matrix (a Mg–Al layered double hydroxide).
Extensive characterization was carried out on the materials, notably
by powder X-ray diffraction and multinuclear (11B, 27Al, 13C, 19F, 25Mg, and 1H) solid state NMR, in order to describe their structure,
particularly in the vicinity of the organoboron species. Three crystalline
phases involving benzoxaborolate anions in association with Ca2+ or Mg2+ cations were also prepared as part of
this work (Mg(C7H6BO(OH)2)2·10H2O, Mg(C7H6BO(OH)2)2·7H2O and Ca3(C7H6BO(OH)2)5(C7H6BO2)·3H2O), in order to assist in the
interpretation of the spectroscopic data. A DFT computational model
of the interlayer space was proposed, which is consistent with the
experimental observations. Several properties of the materials were
then determined with a view of using them as part of novel formulations,
namely the maximum loading capacity toward benzoxaborol(at)es, the
optimal storage conditions, and the release kinetics in simulated
physiological media. All in all, this study serves as a benchmark
not only for the development of novel formulations for benzoxaborole
drugs, but more generally for the preparation of a novel class of
organic–inorganic materials involving benzoxaborol(at)es.