Chemistry in Nanodroplets: Studies of Protonation Sites of Substituted Anilines in Water Clusters Using FT-ICR Sang-Won Lee, ² Heather Cox, William A. Goddard, III, and J. L. Beauchamp* Contribution from the Beckman Institute, California Institute of Technology, Pasadena, California 91125 ReceiVed March 20, 2000 Abstract: Water clusters of protonated substituted anilines generated by an electrospray ion source have been investigated using a Fourier Transform ion cyclotron resonance mass spectrometer. It is observed that evaporation kinetics and cluster distributions are highly dependent on sites of protonation in the substituted anilines. Based on the examination of the water cluster distributions of protonated aniline derivatives, the site of protonation is postulated to be the amine group for aniline, p-anisidine, p-thiomethylaniline, p-ethylaniline, and m-ethylaniline. The water cluster distributions of these compounds display magic number clusters ([M + nH 2 O] + ) for n ) 20, 27, 50, and 52. However, there is no indication of clusters with special stability for m-anisidine and m-thiomethylaniline, suggesting that these compounds protonate on the ring. DFT calculations have been performed to obtain proton affinities for the different sites of protonation in the substituted anilines and are in good agreement with experimental observation. Introduction Solvated ions in the gas phase are frequently referred to as model systems that provide a bridge between the gas-phase chemistry and structure of an isolated ion and its chemistry and structure in solution. This has led to wide-ranging inves- tigations of the solvation of small ions in the gas phase and the effect of solvent on reactivity using various techniques, including high-pressure mass spectrometry, 1 flow tubes, 2 guided ion beam instruments, 3 and Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. 4,5 Direct structural information on small solvated ions has been obtained by infrared predissociation spectroscopy 6 and by theoretical ab initio calculations. 7 Sites of protonation and proton affinities of gas-phase aro- matic compounds have attracted considerable interest. Informa- tion on the role of solvation in determining the site of proto- nation has been obtained through the comparison of gas-phase proton affinities with solution-phase basicities. Various aromatic compounds have exhibited linear correlations between gas-phase proton affinity and solution-phase basicity; failure to do so occurs when the site of protonation in the gas phase differs from that in solution. In the case of substituted anilines, a comparison of the proton affinity of ammonia (853.5 kJ/mol) with that of benzene (750.2 kJ/mol) would suggest that substituted anilines would prefer- entially protonate on the amine group. However, some substi- tuted anilines, such as m-anisidine, m-thiomethylaniline, and m-ethylaniline, have been observed to protonate on the benzene ring in the gas phase due to the increased electron density (relative to aniline) on the benzene ring. 8 In aqueous solution all of these substituted anilines are amine protonated. Highly localized charge in the protonated amine group of an anilinium ion (1) can be more effectively solvated by water molecules than can the extensively delocalized charge of a benzenium ion (2). These substituted anilines have different protonation sites in the gas phase than they do in the solution phase, so it is of interest to determine both their protonation sites in water clusters and the number of water molecules required for proton transfer to occur. Recently, it has been shown that a carefully optimized electrospray source can be used to produce extensively hydrated molecular ions. The water clusters in this study can contain hundreds of molecules, and so the clusters are nanometer size droplets containing ions of interest. Here we report studies of slow evaporation of the “nanodroplets” containing protonated substituted anilines and their utilization in unambiguous deter- mination of protonation sites in the water cluster. These results ² Current address: Battelle-Pacific Northwest National Laboratories, P.O. Box 999 (K8-98), Richland, WA 99352. (1) (a) Kebarle, P.; Tang, L. Anal. Chem. 1993, 65, 972A-986A. (b) Meot-Ner, M.; Speller, C. V. J. Phys. 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Phys. 1997, 106, 6086-6094. (8) Lau, Y. K.; Tse, N. A.; Brown, R. S.; Kebarle, P. J. Am. Chem. Soc. 1981, 103, 6291-6295. 9201 J. Am. Chem. Soc. 2000, 122, 9201-9205 10.1021/ja0009875 CCC: $19.00 © 2000 American Chemical Society Published on Web 09/08/2000