engleski

A Nexus between Theory and Experiment: Non-empirical Quantum Mechanical Computational Methodology Applied to Cucurbit[n]uril•Guest Binding Interactions

A training set of eleven X-ray structure determined biomimetic complexes between cucurbit[n]uril (CB[7 or 8]) hosts and adamantane-/diamantane-ammonium/aminium guests were studied with DFT-D3 quantum mechanical computational methods to afford ΔGcalcd binding energies. Each of the binding geometries is illustrated in 3D virtual reality graphical representations. A novel feature of this work is that the high fidelity of the BLYP-D3/def2-TZVPP choice of DFT functional was proven by comparison with more accurate methods like FN-DMC, CCSD(T)/CBS and MP2.5/CBS, e.g. an MP2.5 interaction energy benchmark calculation (utilizing the kernel energy method) afforded only less than a 2% ΔGcalcd error relative to the protocol's BLYP-D3 in-vacuo value. For the first time, the CB[n]-guest complex binding energy subcomponents [e.g. ΔEdispersion, ΔEelectrostatic, ΔGsolvation, binding entropy (–TΔS) and induced fit Edeformation(host), deformation(guest)] were calculated. These ΔE = Ecomplex – [Ehost + Eguest] binding interactions have yet to be elucidated for CB[n]-guest complexes, and their values provide insight into the role of analogous processes in biological systems. Only a few weeks of computation time were required using this protocol. The deformation (stiffness) and solvation properties (with emphasis on cavity desolvation) of cucurbit[n]uril (n = 5, 6, 7, 8) isolated host molecules were also explored by means of the DFT-D3 method. A high ρ2 = 0.84 correlation coefficient between ΔGexptl and ΔGcalcd was achieved without any scaling of the calculated terms. This linear dependence was utilized for ΔGcalcd predictions of new complexes. The nature of binding, including the role of high energy waters, was also studied. The utility of introduction of tethered [–(CH2)nNH3]+ amino loops attached to N, N-dimethyl-adamantane-1-amine and N, N, N', N'-tetramethyldiamantane-4, 9-diamine skeletons (both from an experimental and a theoretical perspective) is presented here as a promising tool for the achievement of new ultra-high binding guests to CB[7] hosts. Predictions of not yet measured equilibrium constants are presented herein.

DFT ; host-guest complexes ; cucurbit[n]uril ; adamantane-/diamantane-skeleton guests

Znanstveni projekt HAZU - Diamantoidni amini – novi ligandi u supramolekulskim sustavima ; voditelj: Marina Šekutor