Efficient techniques for the synthesis of various nanoparticles possessing particle diameters in the nanometer-scale have been developed over the last two decades. Large-scale synthesis of Au- and CdSe-nanoparticles can be achieved by using the solvated metal atom dispersion technique (SMAD) (1). Fe/Au nanoparticles can be synthesized in inverse micelles by sequentially reducing the Fe(II) and then the Au(III) precursors (2). However, these syntheses often lead to nanoparticles that possess either low or non-existent water solubility. The inability to exist and further react in an aqueous environment severely limits the application of nanoparticles in biological and medicinal systems.

Sonication-assisted ligand-exchange reactions of TOPO (trioctylphosphine oxide) or CTAB (cetyl trimethyl ammonium bromide) against 2,2'-bipyridine, 4,4'-bipyridine or ethylene diamine lead to the migration of the nanoparticles from the non-aqueous to the aqueous phase. TEM indicates that the size-distributions of all three types of nanoparticles remained (almost) constant.

It is of special interest that the nitrogen-containing ligand spheres can be easily exchanged against thiol-functions under ambient conditions. We have employed a cysteine mutant of the mycobacterial porin MspA from M. smegmatis to demonstrate the binding of each of the three classes of nanoparticles. As anticipated, they bind to the inner pore of MspA via ligand exchange with the cysteines in the porin's structure.

(1) Stoeva, S.; Klabunde, K. J.; Sorensen, C. M.; Dragieva, I. J. Am. Chem. Soc. 2002, 124, 2305-2311. (2) Cho, S. J.; Jarrett, B. R.; Louie, A. Y.; Kauzlarich, S. M., Nanotechnology 2006, 17, 640-644.