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 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

Host–Guest Interactions of Sodiumsulfonatomethyleneresorcinarene and Quaternary Ammonium Halides: An Experimental–Computational Analysis of the Guest Inclusion Properties

“…The calculated binding enthalpy is high compared to for example the binding energy reported for complex of protonated tetrasulfonatoresorcinarene and molecular zoledronate -32 kcal mol-1, 53 but the difference can be explained by the high negative charge of the host anion that has not been compensated by other cations in the calculated structures here. To qualitatively access the relative strengths of different types of H-G interactions alternative conformations of B3 + @(A3) 4and B5 + @(A3) 4endo-complexes exhibiting N-methyl, N-butyl, Nethyl and N-phenyl guest to host interactions were optimized.…”

Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters

“…In order to rationalize the biological data reported in Table 1 and to gain deeper insights into the possible interaction mode of calix [8]arene-based multivalent clusters with JBα-man, preliminary molecular docking studies were performed (Figures 3-5 and Figures S91, S92). It is noteworthy that docking approaches have been recently reported for small calixarenes [15,[76][77][78][79]. The multivalent cluster structures were optimized by molecular mechanics calculations and molecular dynamics simulations in a box of water molecules using the YASARA program [80] and AMBER force field [81][82][83][84].…”

Anion Recognition by Organometallic Calixarenes: Analysis from Relativistic DFT Calculations

“…In this sense, molecular calixarenes constitute a suitable family of macrocyclic oligomers for anion recognition, owing to their convenient cavity shape. − Specifically, [1 n ]­metacyclophanes, in which the aromatic units of the calixarenes are linked by methylene bridges in ortho position (Figure ). , Their typical framework, which resembles a cone shaped calix, allows their use for a wide range of applications, such as selective removal of ions from aqueous media, − as drug carrier agents, and in the preparation of synthetic ionic channels, , pores and membranes, − besides their use in catalysis. − …”