An extension 53A6OXY+D to the GROMOS 53A6OXY force field is reported that includes an accurate description of the vicinal diether function. The calibration is based on the model compound 1,2-dimethoxyethane (DXE) and involves a fitting of the relevant torsional-energy parameters against quantum-mechanical (QM) rotational energy profiles for the OCCO and CCOC dihedral angles in vacuum, followed by a validation against experimental conformer populations in the pure liquid and in aqueous mixtures. A systematic comparison between the 53A6, 56A6CARBO, 53A6OXY, and 53A6OXY+D parameter sets is also performed in terms of these properties, as well as in terms of the thermodynamic properties of dimethylether (DME), diethylether (DEE), 1-methoxypropane (MPH), and DXE. Finally, the new parameter set is further validated in the context of polyethers, namely polyethyleneoxide (PEO) and polyethylenegycol (PEG). The 53A6OXY+D set reproduces well the QM rotational profiles of DXE in vacuum (by calibration), the conformational populations of DXE in the pure liquid and in aqueous mixtures, and the experimental thermodynamic pure-liquid and (polar and nonpolar) solvation properties of DME, DEE, MPH, and DXE. In particular, it accounts appropriately for the gauche-effect, both in its solvent-independent stereoelectronic component and in its solvent-dependent dielectric-screening component. In contrast to 53A6OXY, it also suggests a higher affinity of DXE for water compared to octanol, in agreement with the experimental partition coefficient. In the context of aqueous polyethers, the calculated size (Flory) exponent (νg = 0.61) for the molecular-weight dependence of the radius of gyration and persistence length (Lp = 0.39 ± 0.04 nm) agree well with estimates based on experiment or previous simulations with other force fields. The simulations also suggest a picture of aqueous polyethers as "water sponges", in which the diether function "adsorbs" an essentially constant number of water molecules corresponding to first-shell hydrogen-bonded saturation of its oxygen atoms, with a tendency to include other ether oxygen atoms along the chain in the second shell, resulting in "water bridging".
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