First Principles Investigation of Noncovalent Complexation: A [2.2.2]‐Cryptand Ion‐Binding Selectivity Study

Abstract

A first principles methodology, aimed at understanding the roles of molecular conformation and energetics in host-guest binding interactions, is developed and tested on a system that pushes the practical limits of ab initio methods. The binding behavior between the [2.2.2]-cryptand host (4,7,13,16,21,24-hexaoxa-1,10-diaza-bicyclo[8.8.8]hexacosane) and alkali metal cations (Li(+), Na(+), and K(+)) in gas, water, methanol, and acetonitrile is characterized. Hartree-Fock and density functional theory methods are used in concert with crystallographic information to identify gas phase, energy-minimized conformations. Gas phase free energies of binding, with vibrational contributions, are compared to solution-state binding constants through relative binding selectivity analysis. Calculated relative binding free energies qualitatively correlated with solution state experiments only after gas phase metal desolvation is considered. The B3LYP exchange-correlation functional improves theoretical correlations with experimental relative binding free energies. The relevance of gas phase calculations towards understanding binding in condensed phases is discussed. Natural bond orbital methods highlights previously unidentified intramolecular and intermolecular M(+)(222) chemistries, such as an intramolecular n'(O)-->sigma*(CH) hydrogen bond.

A theoretical thermodynamic investigation of cascade reactions in dinuclear octa-azacryptates involving carbon dioxide

“…Among quantum chemical methods for computational modelling of macrocyclic ligands and their complexes, DFT has been successfully applied to the calculation of the thermodynamic parameters for the cryptate formation reaction [26][27][28]. Since hydrogen atoms usually have low X-ray scattering factors and, as a result, their coordinates are not generally determined, structures from crystal data were subject to proton optimisation at the B3LYP/6-31G Table S1).…”

“…The second considers a solvated metal cluster, such as hexa-aqua metal complex [M(H2O) 6 ] 2+ , instead of the bare metal [27]. The third approach combines the first two [28], wherein the first step is the desolvation of the metal ion according to 9 scheme (11) and the second is the bare metal reaction with the cryptand as in scheme (1). Then, the free energy of the reaction is the sum of both steps (∆ 1 + ∆ ).…”

“…This is the difference in the free energy change ∆∆́, as given by eqn. 5, using the following equations [28]. The experimental relative binding selectivity can be expressed as:…”

(4,7,13,16,21,24-Hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane)sodium perchlorate

“…For general background to the macrocyclic polyether 4,7,13,16,21,24-hexaoxa-1,10-diaza-bicyclo[8.8.8]hexacosane, see: Izatt et al (1985); Tait et al (1997); Varga et al (1994); Trend et al (1993); Hamacher et al (1986); Su & Burnette (2008). For related structures, see: Belaj et al (1997); Tehan et al (1974).…”

“…Varga et al (1994) synthesized functionalized 222 for 85 Sr 2+ decorporation in the rat and mouse. J. E. Trend and co-workers (1993) (Su & Burnette, 2008).…”