Title: Ab initio design of drug carriers for zoledronate guest molecule using phosphonated and sulfonated calix[4]arene and calix[4]resorcinarene host molecules,
Abstract: Monomolecular drug carriers based on calix[n]-arenes and -resorcinarenes
containing the interior cavity can enhance the affinity and specificity of the
osteoporosis inhibitor drug zoledronate (ZOD). In this work we investigate the
suitability of nine different calix[4]-arenes and -resorcinarenes based
macrocycles as hosts for the ZOD guest molecule by conducting {\it ab initio}
density functional theory calculations for structures and energetics of
eighteen different host-guest complexes. For the optimized molecular structures
of the free, phosphonated, sulfonated calix[4]-arenes and -resorcinarenes, the
geometric sizes of their interior cavities are measured and compared with those
of the host-guest complexes in order to check the appropriateness for
host-guest complex formation. Our calculations of binding energies indicate
that in gaseous states some of the complexes might be unstable but in aqueous
states almost all of the complexes can be formed spontaneously. Of the two
different docking ways, the insertion of ZOD with the \ce{P-C-P} branch into
the cavity of host is easier than that with the nitrogen containing heterocycle
of ZOD. The work will open a way for developing effective drug delivering
systems for the ZOD drug and promote experimentalists to synthesize them.