No abstract

Solubility is not the only advantage imparted on iodosylbenzene upon the introduction of intramolecular I⋅⋅⋅O secondary bonds. These bonds also enabled the first single‐crystal structural determination of such a species. The structure of 2‐(tBuSO2)C6H4IO (1) reveals how the intramolecular I⋅⋅⋅O bonds can compete with the intermolecular I⋅⋅⋅O bonds which normally dominate the properties of iodosylbenzene. The structure of the corresponding iodylbenzene shows similar features.

The solubility of organic molecules is of critical importance to the pharmaceutical industry; however, robust computational methods to predict this quantity from first-principles are lacking. Solubility can be computed from a thermodynamic cycle that decomposes standard state solubility into the sum of solid–vapor sublimation and vapor–liquid solvation free energies ΔG solubility ° = ΔG sub ° + ΔG solv °. Over the past few decades, alchemical simulation methods to compute solvation free energy using classical force fields have become widely used. However, analogous methods for determining the free energy of the sublimation/deposition phase transition are currently limited by the necessity of a priori knowledge of the atomic coordinates of the crystal. Here, we describe progress toward an alternative scheme based on growth of the asymmetric unit into a crystal via alchemy (GAUCHE). GAUCHE computes deposition free energy ΔG dep ° = −ΔG sub ° = −k B T ln(V c/V g) + ΔG AU + ΔG AU→UC as the sum of an entropic term to account for compressing a vapor at 1 M standard state (V g) into the molar volume of the crystal (V c), where k B is Boltzmann’s constant and T is temperature in degrees Kelvin, plus two simulation steps. In the first simulation step, the deposition free energy ΔG AU for a system composed of only N AU asymmetric unit (AU) molecule(s) is computed beginning from an arbitrary conformation in vacuum. In the second simulation step, the change in free energy ΔG AU→UC to expand the asymmetric unit degrees of freedom into a unit cell (UC) composed of N UC independent molecules is computed. This latter step accounts for the favorable free energy of removing the constraint that every symmetry mate of the asymmetric unit has an identical conformation and intermolecular interactions. The current work is based on NVT simulations, which requires knowledge of the crystal space group and unit cell parameters from experiment, but not a priori knowledge of crystalline atomic coordinates. GAUCHE was applied to 5 organic molecules whose sublimation free energy has been measured experimentally, based on the polarizable AMOEBA force field and more than a microsecond of sampling per compound in the program Force Field X. The mean unsigned and RMS errors were only 1.6 and 1.7 kcal/mol, respectively, which indicates that GAUCHE is capable of accurate prediction of absolute sublimation thermodynamics.

Iodonium ylides of the form ArINSO 2 Ar′ (Ar ) m-tolyl, Ar′ ) p-nitrophenyl (1); Ar ) m-tolyl, Ar′ ) phenyl (2); Ar ) m-tolyl, Ar′ ) p-tolyl (3); Ar, Ar′ ) p-tolyl (4)) have been prepared and crystallographically characterized. Comparisons to previously structurally characterized members of this class of materials (PhINTs (Ts ) p-toluenesulfonyl), o-TolylINTs, MesINTs) demonstrate that apparently minor perturbations of the aromatic rings have substantial consequences on the supramolecular assemblies of these materials. The structures range from zigzag polymers (PhINTs, MesINTs), linear polymers (o-TolylINTs), layered structures (1), two-dimensional ladders (2, 3, o-TolylINTs), to even three-dimensional stepladders (4). Ab initio calculations for a model molecule, PhINSO 2 -Ph, corroborate the presence of a I-N single bond and show considerable charges being localized on the I, N, S, and O atoms (+, -, +, andcharges, respectively). Extensive attractive networks of I‚‚‚O and I‚‚‚N secondary bonds thus dominate the solid-state polymers. Within the monomeric units of ArINSO 2 Ar′, a U-turn-shaped motif is observed. This structural shape appears to optimize secondary bonding contacts between charged INSO 2 arrays. The structures of ArINSO 2 Ar′ have been systematically characterized.