title: A Nexus between Theory and Experiment: Non-Empirical Quantum Mechanical Computational Methodology Applied to Cucurbit[n]uril⋅Guest Binding Interactions.
abstract: A training set of eleven X-ray structures determined for 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 ΔGcalcdbinding energies. A novel feature of this work is that the fidelity of the BLYP-D3/def2-TZVPP choice of DFT functional was proven by comparison with more accurate methods. For the first time, the CB[n]⋅guest complex binding energy subcomponents [for example, ΔEdispersion, ΔEelectrostatic, ΔGsolvation, binding entropy (-TΔS), and induced fit Edeformation(host), Edeformation(guest)] were calculated. Only a few weeks of computation time per complex were required by 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 ΔGexptland ΔGcalcdwas achieved without any scaling of the calculated terms (at 298 K). This linear dependence was utilized for ΔGcalcdpredictions of new complexes. The nature of binding, including the role of high energy water molecules, 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'-tetramethyl diamantane-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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Flemingovo náměstí 2, Prague 6, 160 10, Czech Republic.|Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University in Prague, Albertov 6, 12843, Prague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Hostaš
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sigwalt
authors.affiliation: Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Šekutor
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Flemingovo náměstí 2, Prague 6, 160 10, Czech Republic.|Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Palacký University, 77146, Olomouc, Czech Republic.
authors.forename: Haresh
authors.initials: H
authors.lastname: Ajani
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Palacký University, 77146, Olomouc, Czech Republic.
authors.forename: Matúš
authors.initials: M
authors.lastname: Dubecký
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Flemingovo náměstí 2, Prague 6, 160 10, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Řezáč
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Zavalij
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Cao
authors.affiliation: Scientific Computing Unit, Johannes Kepler University Linz, 4040, Linz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Wohlschlager
authors.affiliation: Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.
authors.forename: Kata
authors.initials: K
authors.lastname: Mlinarić-Majerski
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Lyle
authors.initials: L
authors.lastname: Isaacs
authors.affiliation: Institut für Organische Chemie, Johannes Kepler Universität Linz, 4040, Linz, Austria), Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105 (Israel.
authors.forename: Robert
authors.initials: R
authors.lastname: Glaser
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Flemingovo náměstí 2, Prague 6, 160 10, Czech Republic.|Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Palacký University, 77146, Olomouc, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hobza
keywords: BLYP-D3 quantum mechanical calculations; adamantane-/diamantane-skeleton guests; biomimetic complexes; cucurbit[n]uril; host-guest complexes; primary ammonium loops