The Binding Energy of Two Nitrilotriacetate Groups Sharing a Nickel Ion David Tareste, ² Fre ´ de ´ ric Pincet, ² Marie Brellier, ‡ Charles Mioskowski, ‡ and E Ä ric Perez* ,² Contribution from the Laboratoire de Physique Statistique de l’Ecole Normale Supe ´ rieure, 24, rue Lhomond, 75005 Paris, France, and Laboratoire de Synthe ` se Bio-Organique, Faculte ´ de Pharmacie, 74, Route du Rhin, 67401 Illkirch, France Received October 26, 2004; E-mail: perez@lps.ens.fr Abstract: Among the various molecular interactions used to construct supramolecular self-assembling systems, homoliganded metallic NTA-Ni-NTA complexes have received little attention despite their considerable potential applications, such as the connection of different biochemical functions. The stability of this complex is investigated here by using two concordant nanotechniques (surface forces apparatus and vesicle micromanipulation) that allow direct measurements of adhesion energies due to the chelation of nickel ions by nitrilotriacetate (NTA) groups grafted on surfaces. We show that two NTA groups can share a nickel ion, and that the association of a Ni-NTA complex with an NTA group has a molecular binding energy of 1.4 kcal/mol. Binding measurements in bulk by isothermal titration calorimetry experiments give the same value and, furthermore, indicate that the Ni-NTA chelation bond is about five times stronger than the NTA-Ni-NTA one. This first direct proof and quantification of the simultaneous chelation of a nickel ion by two NTA groups sheds new light on association dynamics involving chelation processes and offers perspectives for the development of new supramolecular assemblies and anchoring strategies. Introduction Supramolecular self-assembling systems are generally based on noncovalent cooperative interactions which permit the construction of highly sophisticated structures presenting tailored functions. 1-3 The weak interactions involved in these systems include hydrophobic interactions, hydrogen bonding, π-stacking interactions, metal coordination bonding, and specific ligand- receptor interactions. One of the major goals in supramolecular chemistry is to control the structure and dynamic of matter through self-organization. This includes a characterization, at the molecular level, of the interactions that hold the building blocks together. Recent advances in nanoscale force and adhesion measurements have already allowed the quantification of hydrogen bonding interactions, 4,5 but many other weak interactions, such as metal-ligand binding, remain poorly described. Heteroliganded metallic complexes have received consider- able attention during the past few years since genetically engineered His-tagged proteins were found to bind specifically to Ni-NTA moieties, thus forming a His-Ni-NTA ternary complex. Today, such a complex is extensively used for purification purposes, surface functionalization by proteins, and bidimensional crystallization through Ni-NTA functionalized lipids. 6-11 Homoliganded metallic complexes, such as metal- bis(carboxylate), 12,13 metal-bis(phosphonate), 14,15 and metal- bis(terpyridine), 16-18 have also been used to generate supramo- lecular systems with original structures and novel optical, electric, or magnetic properties. Many potential applications could be derived from the formation of NTA-Ni-NTA ² Laboratoire de Physique Statistique de l’Ecole Normale Supe ´rieure. ‡ Laboratoire de Synthe `se Bio-Organique. (1) Whitesides, G. M.; Mathias, J. P.; Seto, C. T. Science 1991, 254, 1312- 1319. (2) Lehn, J. M. Science 2002, 295, 2400-2403. (3) Dmitriev, A.; Spillmann, H.; Lin, N.; Barth, J. V.; Kern, K. Angew. Chem., Int. Ed. 2003, 42, 2670-2673. (4) Pincet, F.; Perez, E.; Bryant, G.; Lebeau, L.; Mioskowski, C. Phys. ReV. Lett. 1994, 73, 2780-2783. (5) Tareste, D.; Pincet, F.; Perez, E.; Rickling, S.; Mioskowski, C.; Lebeau, L. Biophys. J. 2002, 83, 3675-3681. (6) Hochuli, E.; Bannwarth, W.; Dobeli, H.; Gentz, R.; Stuber, D. Biotechnology 1988, 6, 1321-1325. (7) Schmitt, L.; Dietrich, C.; Tampe, R. J. Am. Chem. Soc. 1994, 116, 8485- 8491. (8) Venien-Bryan, C.; Balavoine, F.; Toussaint, B.; Mioskowski, C.; Hewat, E. A.; Helme, B.; Vignais, P. M. J. Mol. Biol. 1997, 274, 687-692. (9) Wilson-Kubalek, E. M.; Brown, R. E.; Celia, H.; Milligan, R. A. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 8040-8045. (10) Bischler, N.; Balavoine, F.; Milkereit, P.; Tschochner, H.; Mioskowski, C.; Schultz, P. Biophys. J. 1998, 74, 1522-1532. (11) Lebeau, L.; Lach, F.; Venien-Bryan, C.; Renault, A.; Dietrich, J.; Jahn, T.; Palmgren, M. G.; Kuhlbrandt, W.; Mioskowski, C. J. Mol. Biol. 2001, 308, 639-647. (12) Guo, S. W.; Konopny, L.; Popovitz-Biro, R.; Cohen, H.; Porteanu, H.; Lifshitz, E.; Lahav, M. J. Am. Chem. Soc. 1999, 121, 9589-9598. (13) Waggoner, T. A.; Last, J. A.; Kotula, P. G.; Sasaki, D. Y. J. Am. Chem. Soc. 2001, 123, 496-497. (14) Cao, G.; Hong, H. G.; Mallouk, T. E. Acc. Chem. Res. 1992, 25, 420- 427. (15) Benitez, I. O.; Bujoli, B.; Camus, L. J.; Lee, C. M.; Odobel, F.; Talham, D. R. J. Am. Chem. Soc. 2002, 124, 4363-4370. (16) Liang, Y. W.; Schmehl, R. H. J. Chem. Soc., Chem. Commun. 1995, 1007- 1008. (17) Constable, E. C.; Meier, W.; Nardin, C.; Mundwiler, S. Chem. Commun. 1999, 1483-1484. (18) Lohmeijer, B. G. G.; Schubert, U. S. Angew. Chem., Int. Ed. 2002, 41, 3825-3829. Published on Web 02/26/2005 10.1021/ja043525q CCC: $30.25 © 2005 American Chemical Society J. AM. CHEM. SOC. 2005, 127, 3879-3884 9 3879