Sila-Ibuprofen

The
synthesis, characterization, biological activity, and toxicology
of sila-ibuprofen, a silicon derivative of the most common nonsteroidal
anti-inflammatory drug, is reported. The key improvements compared
with ibuprofen are a four times higher solubility in physiological
media and a lower melting enthalpy, which are attributed to the carbon–silicon
switch. The improved solubility is of interest for postsurgical intravenous
administration. A potential for pain relief is rationalized via inhibition
experiments of cyclooxygenases I and II (COX-I and COX-II) as well
as via a set of newly developed methods that combine molecular dynamics,
quantum chemistry, and quantum crystallography. The binding affinity
of sila-ibuprofen to COX-I and COX-II is quantified in terms of London
dispersion and electrostatic interactions in the active receptor site.
This study not only shows the potential of sila-ibuprofen for medicinal
application but also improves our understanding of the mechanism of
action of the inhibition process.