Soto-Delgado et al. studied the reaction of cyclopentadiene and methyl vinyl ketone in both water and methanol, using a combined QM/MM-MD approach . The activation free-energy barrier in methanol is 2.1 kcal/mol higher than in water, which is within 0.1 kcal/mol from the experimental difference (a rate deceleration of 2 orders of magnitude). Again, the ability of the solvent and transition state to hydrogen bond, which is stronger and longer-lived in water than in methanol, contributes to this effect. Kiselev et al. compared reaction rates of 9-(hydroxymethyl)anthracene and 9,10bis(hydroxymethyl)anthracene with maleic anhydride, N-ethylmaleimide and N-phenylmaleimide, in organic and water-1,4-dioxane cosolvents . It was found that even those reactants which do not hydrogen-bond with water experienced reaction rate acceleration in water, depending on the structure of the diene. The organic cosolvents reduced the reaction rate, also depending on the polarity of the reactants.