Free Energy Perturbation Calculations for Small Molecules

FREE ENERGY PERTURBATION CALCULATIONS FOR SMALL MOLECULES 

Summarized in the next section are the small-molecule properties reported from free energy calculations. Most of the published results suggest that existing methodology can provide results in good agreement with experimental data. 

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Free Energy Perturbation Calculations for Small Molecules 22S... 

MD simulations of halide anions [X]- and their inclusion complexes [X] c [L4+] with a macrotricyclic tetrahedral host built from four quaternary ammonium sites dissolved in [C4mim][PF6] were carried out [118]. In the dry IL the uncomplexed halides were surrounded by four to five [C4mim]+ cations which bond via hydrogen bonding to facial coordination. The first solvation shell of [Cl]-, [Br], and [I] comprised of three to four cations next to four H20 molecules for the humid system. The solvation of the [L4+] host and of its [X]-1 [L4+] complex mainly involved anions in the dry IL, and additional H20 molecules in the humid IL. Free energy perturbation calculations predicted that in the dry liquid [F] is preferred over [Cl] , [Br] and [I]- in contrast to the aqueous solution where [L4+] was selective for [Cl]-. In the humid liquid no [F] /[C1] discrimination was observed, showing the importance of small amounts of water on the complexation selectivity [118]. 

The perturbation calculations of intermolecular energies are tedious, even for small molecules. On the other hand, the perturbation approach is advantageous (over the variational supermolecule approach, see below) because (i) the small interaction energy is calculated directly rather than as a difference between two large, almost identical, numbers ( ab and a + E ), (ii) the individual contributions to the intermolecular energy have a clear physical meaning, (iii) SAPT terms are free of the basis set superposition error (BSSE, see below) and (iv) each term can be evaluated using a different basis set, the most appropriate and economic for that particular component. 

SAPT avoids the subtraction of large energy values that is necessarily part of a supermolecule ab initio calculation. A supermolecule calculation obtains the interaction energy of monomers A and B, AVab, as Tab - Va - Vb. whereas SAPT finds AVab directly. The interaction evaluated in SAPT is defined so as to be free of BSSE however, the other requirements on basis-set quality and for correlation effects still hold. SAPT has yielded highly accurate interaction data, first for rare gas atoms interacting with small molecules [72 74] and more recently with molecule molecule clusters such as the CO2 dimer [75]. Further examples are the very accurate results achieved for Ne HCN [76] and a parr potential for water [77]. Another example study of perturbative treatment of the interaction potential has been a study of rare gas HCN clusters [78] which included vibrational analysis. 

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