title: Monte Carlo structure simulations for aqueous 1,4-dioxane solutions.
abstract: Monte Carlo simulations in the NpT ensembles have been performed for the structure exploration of aqueous 1,4-dioxane solutions. Three different systems with all-atom dioxane:TIP4P water molar compositions of 2:500 (code:D2), 8:465 (D8), and 17:425 (D17) modeled solutions of 0.22, 0.88, and 1.86 mol/dm3 concentrations, respectively, at T = 298 K and p = 1 atm. The calculated solution densities increase from 0.992 to 1.002 g/cm3 with increasing dioxane concentration and approach the experimentally determined densities within 1%. This close agreement was achieved by utilizing RESP charges fitted to the in-solution IEF-PCM/B3LYP/6-31G* electrostatic potential of dioxane taken in its chair conformation and recently developed C, H steric parameters for ethers for calculations with a 12-6-1 all-atom potential. Solution structure analyses pointed out that the dioxane molecules arrange in the solutions with favorable distances of 4-8 angstroms for the ring symmetry centers. Within this range not only pairs of rings but triangular triads and tetrads have also been observed with center-center distances <8 angstroms. For the D8 system, about 25% of the sampled configurations included such a triad. In the case of the D17 model, two simulations starting from different solution configuration predicted different degrees for the dioxane aggregation in aqueous solution. In the more aggregated structure 3-21 triads are consistently maintained and 1-2 tetrads are formed in 58% of the configurations. Each dioxane oxygen forms about one hydrogen bond, on average, to a water molecule in the 0.22-1.86 molar range. The most likely O(dioxane)...H(water) hydrogen bond distance is 1.75-1.80 angstroms compared to the optimal distance of 1.72 angstroms in the isolated dimer. The optimal dioxane-water interaction energy of -5.65 kcal/mol indicates a remarkable hydrogen-bond acceptor character for dioxane.
authors.affiliation: Department of Medicinal and Biological Chemistry and the Center for Drug Design and Development, The University of Toledo, Toledo, Ohio 43606-3390, USA. pnagy@utnet.utoledo.edu
authors.forename: Peter I
authors.initials: PI
authors.lastname: Nagy
authors.forename: Gergely
authors.initials: G
authors.lastname: Völgyi
authors.forename: Krisztina
authors.initials: K
authors.lastname: Takács-Novák
mesh_terms: D003198:Computer Simulation; D004146:Dioxanes / Q000737:chemistry*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009010:Monte Carlo Method; D012996:Solutions; D014867:Water
chemical_list: D004146:Dioxanes; D012996:Solutions; D014867:Water; C025223:1,4-dioxane