Novel Chiral “Calixsalen” Macrocycle and Chiral Robson-type Macrocyclic Complexes Jian Gao,* ,² Joseph H. Reibenspies, ‡ Ralph A. Zingaro, ‡ F. Ross Woolley, ² Arthur E. Martell, ‡,§ and Abraham Clearfield ‡ Department of Radiology, UniVersity of Texas Health Science Center, San Antonio, Texas 78229-3900, and Department of Chemistry, Texas A & M UniVersity, College Station, Texas 77843-3255 Received June 23, 2004 A family of novel chiral “calixsalen” Schiff base macrocycles R,R-H 3 L4, R,R-H 3 L5, containing three chiral diamino moieties were synthesized by an efficient self-assembly and characterized by 1 H and 13 C NMR, mass spectrometry, and X-ray diffraction. The systematic synthesis, structure, and coordination properties of the [2 + 2] and [3 + 3] Robson-type Schiff base macrocyclic mono-, di-, tri-, and tetranuclear metal complexes were explored. Introduction The presence of multinuclear sites has long been cited in an attempt to explain the function of many biologically important enzymes. 1 Substantial effort has been devoted to synthesizing model complexes that would permit the reliable simulation of enzyme behaviors experimentally to better understand their function. Schiff base Robson-type macro- cycles containing two bridging phenol groups have been widely used to synthesize homo- and hetero-dinuclear complexes. 2 Most investigations of these metal complexes are an outgrowth of bioinorganic chemistry and enzymatic catalysis research. 3 Typically, Robson-type macrocyclic complexes have been derived from the template condensation of achiral diamines such as ethylenediamine or diethylene- triamine and 2-hydroxy-5-methyl-benzene-1,3-dicarbalde- hyde. However, the use of chiral diamines such as 1R,2R- diaminocyclohexane (R,R-DACH), 1R,2R-diphenylethylene- diamine (R,R-DPEN), and R-1,1′-binaphthalenyl-2,2′-diamine (R-BNDA) (see Scheme 1) in the construction of chiral Schiff base Robson-type macrocycles has received only limited study. Our primary interest in these compounds arises from the combination of the synthetic and structural chemistry of chiral macrocycles and how they differ from their achiral counterparts. 4 Unlike linear ethylenediamine for example, chiral diamine compounds have specific stereogenic con- formation and structural rigidity (see Scheme 1). The conformational stability and shape persistency of chiral cyclic structures have been postulated to arise from the structural rigidity and chirality of their assembly moieties. 5 We speculated that a new type of chiral “calixsalen” macrocycle could be constructed using the characteristic of simultaneous self-assembly of the chiral diamines with 2-hydroxy-5- * To whom correspondence should be addressed. E-mail: gaoj2@ uthscsa.edu. ² University of Texas Health Science Center. ‡ Texas A & M University. § Dr. Martell died suddenly in October of 2003. He laid the foundation that made this paper possible and contributed actively until his untimely passing. (1) (a) Lippard, S. J.; Berg, J. M. In Principles of Bioinorganic Chemistry; University Science Books: Mill Valley, CA, 1994. (b) Cole, A. P.; Root, D. E.; Mukherjee, P.; Solomon, E. I.; Stack, T. D. P. Science 1996, 273, 1848. (c) Solomon, E. I.; Sundaram, U. M.; Machonkin, T. E. Chem. ReV. 1996, 96, 2563. (d) Feig, A. L.; Lippard, S. J. Chem. ReV. 1994, 94, 759. (2) (a) Pilkington, N. H.; Robson, R. Aust. J. Chem. 1970, 23, 2225. (b) Das, R.; Nag, K. Inorg. Chem. 1991, 30, 2831. (c) Bosnich, B. Inorg. Chem. 1999, 38, 2554. (3) (a) Long, R. C.; Hendrickson, D. N. J. Am Chem. Soc. 1983, 105, 1513. (b) Atkins, A.; Black, D.; Blake, A. J.; Marin-Becerra, A.; Persons, S.; Ruiz-Ramirez, L.; Schroder, M. Chem. Commun. 1996, 457. (c) Yoncmura, M.; Usuki, N.; Nakamara, Y.; Ohba, M.; Okawa, H. J. Chem. Soc., Dalton Trans. 2000, 3624. (4) (a) Li, Z.; Jablonski, C. Chem. Commun. 1999, 1531. (b) Chadim, M.; Budesinsky, M.; Hodacova, J.; Zavada, J.; Junk, P. C. Tetrahe- dron: Asymmetry 2001, 12, 127. (c) Kuhnert, N.; Strabnig, C.; Lopez- Periago, A. M. Tetrahedron: Asymmetry 2002, 13, 123. (5) (a) Gawronski, J.; Kolbon, H.; Kwit, M.; Katrusiak, A. J. Org. Chem. 2000, 65, 5768. (b) Ricci, R.; Pasini, D. Org. Biomol. Chem. 2003, 1, 3261. Scheme 1 Inorg. Chem. 2005, 44, 232-241 232 Inorganic Chemistry, Vol. 44, No. 2, 2005 10.1021/ic049181m CCC: $30.25 © 2005 American Chemical Society Published on Web 12/24/2004