Cation–Anion Hydrogen Bonds: A New Class of Hydrogen Bonds That Extends Their Strength beyond the Covalent Limit. A Theoretical Characterization

The existence of O–H···O hydrogen bonds having a strength within the −80 to −210 kcal/mol range, that is, in the range of strength of covalent bonds and well beyond the so-called covalent limit (−50 kcal/mol), is reported on complexes where the O–H proton donor and O acceptor groups are located in ions of opposite sign. A complete analysis of short distance O–H···O hydrogen bonds between charged fragments was performed for cases where the OH and O groups are both located on charged molecules. It shows that these interactions (a) are nonsymmetrical for the O–H and H···O distances, (b) have a noncovalent H···O bond critical point, and (c) have a strong and energetically stable electrostatic component when the OH and O groups are located in oppositely charged molecules. These cation–anion O–H···O interactions are energetically stable, satisfy the usual topology for hydrogen bonds, HBs, and also have the same directionality found in other HBs. Therefore, they should be considered as a new class of HBs, the <i>cation–anion hydrogen bonds</i>

Racemic Naproxen: A Multidisciplinary Structural and Thermodynamic Comparison with the Enantiopure Form

Following the computational prediction that (<i>RS</i>)-naproxen would be more stable than the therapeutically used and more studied homochiral (<i>S</i>)-naproxen, we performed an interdisciplinary study contrasting the two compounds. The crystal structure of the racemic compound was solved from powder X-ray diffraction data (<i>Pbca</i>) and showed no packing similarity with the homochiral structure (<i>P</i>2₁). The binary melting point phase diagram was constructed to confirm the nature of the racemic species, and differential scanning calorimetric and solubility measurements were used to estimate the enthalpy difference between the crystals (Δ<i>H</i>_{<i>R</i>+<i>S</i>→<i>RS</i>}^cry) to be −1.5 ± 0.3 kJ·mol^–1 at <i>T</i> ∼ 156 °C and −2.4 ± 1.0 kJ·mol^–1 in the range 10–40 °C. A comparison of the different approximations involved in estimating Δ<i>H</i>_{<i>R</i>+<i>S</i>→<i>RS</i>}^cry implied that the difference in the lattice energies overestimated the stability of the (<i>RS</i>) crystal. The naproxen lattice energy landscape confirmed that all the practically important crystal structures have been found and characterized and provided insights into the crystal growth problems of the racemic form. This highlights the complementarity of computational modeling in investigating chiral crystallization