Received: 18 February 2008, Revised: 30 April 2008, Accepted: 29 May 2008, Published online in Wiley InterScience: 8 July 2008 Ultrasonic detection of hydrophobic interactions: a quantitative approach Ants Tuulmets a * , Jaak Ja ¨rv a , Siim Salmar a and Giancarlo Cravotto b Kinetic effects of sonication on ester hydrolysis and tert-butyl chloride solvolysis, studied in ethanol–water binary solvent, are discussed in terms of quantitative relationships between their magnitude and the hydrophobicity of reagents. A number of conclusions were drawn from the observed linear free-energy (LFE) relationships. Independent of reaction mechanism, the decrease in reaction rates with increasing ethanol content in the solvent is mainly due to hydrophobic stabilization of the ground state. While hydrophobic species can be hidden in the ethanol clusters present in the region X EtOH > 0.15, at lower ethanol contents hydrophobic reagents are weakly solvated and the hydrophobic stabilization can be easily overcome by sonication. Copyright ß 2008 John Wiley & Sons, Ltd. Keywords: ester hydrolysis; hydrophobic interactions; organic–aqueous solutions; sonication effects; solvolysis reactions INTRODUCTION Hydrophobic effects play an important role in many chemical processes in aqueous solutions. Two phenomena can be distinguished: hydrophobic hydration and hydrophobic inter- action (HI). Hydrophobic hydration denotes how apolar solutes affect the organization of water molecules in their immediate vicinity. The HI is the tendency of apolar species to aggregate in aqueous solutions to reduce their contact surface with water. HI can lead to pairwise interactions, known as encounter complexes, to well-defined host–guest complexes, to the formation of small clusters of molecules, or to large aggregates. [1–5] HI between apolar molecules or apolar parts of molecules in water are important noncovalent driving forces for inter- and intramolecular binding and assembly processes, taking place in aqueous chemistry and biochemistry. [1–5] In aqueous systems these interactions can strongly influence chemical equilibria and reaction rates. [3–9] For example, in the hydrolysis of esters, HIs (the formation of hydrophobically stabilized encounter complexes or clusters with co-solutes) make the ester less reactive. [10–14] On the other hand, the Diels–Alder reaction [15] and the benzoin condensation [16] are dramatically accelerated when carried out in water rather than in organic solvents. Such rate enhancements mostly result from the packing of hydrophobic surfaces of these reagents in the transition state, whose energy is lowered as hydrocarbon–water contacts are minimized. [2–5] Although HI can be studied by a large variety of experimental and computational techniques, the determination of chemical reactivity has a special position among them. [4,5,17,18] Indeed, rate constants can usually be determined with so high a precision, that small hydrophobic effects can thus be detected. Our contribution to HI studies consists in applying power ultrasound to kinetic investigation of polar (ionic) homogeneous reactions in solutions, mainly in ethanol–water binary mix- tures. [19–23] Ultrasonic acceleration effects on chemical processes are widely exploited both in the laboratory and industrial prac- tice. [24–26] Sonication mostly affects reaction rates, yields, and in some cases the ratios of reaction products. Besides bringing about mechanical effects, cavitation induced by sonication can promote many homogeneous and heterogeneous reactions by generating free radicals which give rise to chain reactions in solution. Sonication studies of solvolysis/hydrolysis reactions in aqueous– organic binary solvents have brought to light specific solute– solvent interactions and hydrophobic effects that are not manifested in conventional kinetic investigations. [19–23,27–29] It was concluded that in these cases the sonochemical effects may be related to the perturbation of the molecular structure of the solvent and, more critically, to the destruction of hydrophobic solute–solvent interactions. However, conclusions drawn so far have been merely qualitative deductions based on observed sonication effects in reaction kinetics. In this paper, we show that a quantitative correlation of kinetic sonication effects with substrate hydro- phobicity reveals novel details of solvation phenomena and HI in solutions. RESULTS AND DISCUSSION A comprehensive investigation of sonication effects on polar homogeneous reactions was first performed by Mason’s group. [27,28] An unexpectedly complicated dependence of the effect (k son /k) on the composition of ethanol–water binary solvent was found for the solvolysis reaction of tert-butyl chloride. The authors concluded that the application of ultrasound to the reaction disrupted the binary solvent structure, thus permitting a (www.interscience.wiley.com) DOI 10.1002/poc.1415 Research Article * Correspondence to: A. Tuulmets, Institute of Chemistry, University of Tartu, Jakobi 2, 51014 Tartu, Estonia. E-mail: ants.tuulmets@ut.ee a A. Tuulmets, J. Ja ¨rv, S. Salmar Institute of Chemistry, University of Tartu, Jakobi 2, 51014 Tartu, Estonia b G. Cravotto Dipartimento di Scienza e Tecnologia del Farmaco, Universita ` di Torino, Via P. Giuria 9, I-10125 Torino, Italy J. Phys. Org. Chem. 2008, 21 1002–1006 Copyright ß 2008 John Wiley & Sons, Ltd. 1002