J. Am. Chem. zyxwvut SOC. 1992, 114, zyxwvuts 10647-10649 Scheme I. Solid-Phase Assembly of an N-Substituted Glycine from Two Submonomers 10647 zyxwvutsrqpo 1 - zyxwvutsrqponmlkjih R DMSO S7EP zyxwvutsrqp 1 Table I. Oligo(N-Substituted Glycines) Prepared by the Submonomer Method Oligomer Crude product characteristics purity (%) zyxwvutsrqp a yield ("/.) mass (MH+~ 90 74 79 70 83 83 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 52 63 86d 583.5 753.2 713.4 1204.1 683.3 503.3 1018.4 588.4 2850.9 'Determined by HPLC. )etermined from dry weight. 'Liquid- * Made from Boc-NH- matrix secondary-ion mass spectrometry. (CHA~NHI. Using optimized synthetic conditions2 eight penta(NSGs) were prepared by the submonomer method from a variety of amines, including poorly nucleophilic, sterically-hindered, and side- chain-protected amines. The punty, yields, and mass spectrometry data on the pentamers are shown in Table I. zyxwvutsr All compounds were successfully synthesized as established by mass spectrometry, with isolated crude yields between 52 and 90% and purities generally greater than 85% by HPLCS5 A 25-mer, [(N-butylgIy~ine)~(N-(3-aminopropyl)glycine)] 5, was synthesized by the submonomer method, thereby demonstrating the utility of this method for the preparation of longer oligomers. Mass spectroscopy confirmed the identity of this compound (MH+ = 2850.9), which was obtained in 86% yield and 65% purity by HPLC.5 The efficient synthesis of a wide variety of oligomeric NSGs using robotic synthesis technology, as presented here, makes these polymers attractive candidates for the generation and rapid screening of diverse peptidomimetic libraries. The compatibility of this method with conventional peptide synthesis should allow the incorporation of novel structures into peptides. Furthermore, the solid-phase submonomer method should allow the efficient STEP2 synthesis of a wide variety of novel N-substituted biopolymers. Acknowledgment. The authors thank the following people at Chiron for their assistance with chemistry and laboratory auto- mation: Steven C. Banville, Robert s. Kania, and Dr. Charles K. Marlowe. Bioorganometallic Chemistry. 1. Synthetic and Structural Studies in the Reactions of a Nucleobase and Several Nucleosides with a ($-Pentamethylcyclopentadienyl)rhodium Aqua Complex David P. Smith,+ Eduardo Baralt: Bruce Morales,' Marilyn M. Olmstead,t Marcos F. Maestre,t and Richard H. Fish*st Lawrence Berkeley Laboratory University zyx of California Berkeley, California 94720 Department of Chemistry, University of California Davis, California 95616 Received July 20, 1992 Interactions of metal complexes with DNA/RNA nucleobases, nucleosides, nucleotides, and oligonucleotideshave been extensively studied in order to determine the mode of action of these metal complexes as a consequence of drug activity, as useful tools for molecular biology, and as regulators of gene expression.' The great majority of these bonding studies have been carried out with inorganic complexes,2 while few have utilized organometallic compound^.^ Author to whom correspondence should be addressed. 1 University of California. (1) (a) Tullius, T. D. In Metal-DNA Chemistry; Tullius, T. D., Ed.; ACS Symposium Series 402; American Chemical Society: Washington, D. C., 1989; Chapter 1 and references therein. (b) Barton, J. K. Comments Inorg. Chem. 1985, 3, 321 and references therein. (c) Pyle, A. M.; Barton, J. K. In Progress in Inorganic Chemistry, Bioinorganic Chemistry; Lippard, S. J., Ed.; J. Wiley and Sons: New York, 1990; Vol. 38, p 413 and references therein. (2) (a) Marzilli, L. G. In Progress in Inorganic Chemistry; Lippard, S. J., Ed.; J. Wiley and Sons: New York, 1977; Vol. 23, p 255 and references therein. (b) Howe-Grant, M. E.; Lippard, S. J. Met. zyxw Ions Biol. Syst. 1980, 11, 63 and references therein. (b) Raudaschl-Sieber, G.; Schollhorn, H.; Thewalt, U.; Lippert, B. J. Am. Chem. SOC. 1985, 107, 3591. (c) Reily, M. D.; Hambley, T. W.; Marzilli, L. G. J. Am. Chem. Soc. 1988,110, 2999. (d) Alink, M. A.; Nakahara, H.; Hirano, T.; Inagaki, K.; Hakanishi, M.; Kidani, Y.; Reedijk, J. Inorg. Chem. 1991, 30, 1236 and references therein. (e) Reily, M. D.; Marzilli, L. G. J. Am. Chem. Soc. 1986, 108, 8299. (fJ Qu, Y.; Farrell, N. J. Am. Chem. Soc. 1991,113,4851 and references therein. (g) Caradonna, J. P.; Lippard, S. J.; Gait, M. J.; Singh, M. J. Am. Chem. SOC. 1982, 104, 5793. (h) Marcelis, A. T. M.; den Hartog, J. H. J.; Reedijk, J. J. Am. Chem. SOC. 1982, 104, 2664. (i) Sherman, S. E.; Gibson, D.; Wang, A. H.4.; Lippard, S. J. J. Am. Chem. SOC. 1988, 110, 7368. 6) Mukundan, S., Jr.; Xu, Y.; Zon, G.; Marzilli, L. G. J. Am. Chem. SOC. 1991, 113, 3021. (I) Pneumatikakis, G.; Hadjiliadis, H. J. Chem. Soc., Dalton Trans. 1979, 596. (m) Rainen, L.; Howard, R. A,; Kimball, A. P.; Bear, J. L. Inorg. Chem. 1975, 14, 2752. (n) Torres, L. M.; Marzilli, L. G. J. Am. Chem. SOC. 1991, 113, 4678. (0) Scheller, K. H.; Mitchell, P. R.; Prijs, B.; Sigel, H. J. Am. Chem. Soc. 1981,103, 247. (p) Sigel, H. In Metal-DNA Chemistry; Tullius, T. D., Ed.; ACS Symposium Series 402; American Chemical Society: Washington, D. C., 1989; Chapter 11 and references therein. (9) Hodgson, D. J. In Progress in Inorganic Chemistry; Lippard, S. J., Ed.; J. Wiley and Sons: New York, 1977; Vol. 23, p 211. (3) (a) Kuo, L. Y.; Kanatzdis, M. G.; Marks, T. J. J. Am. Chem. Soc. 1987,109,7207. (b) Toney, J. H.; Brock, C. P.; Marks, T. J. J. Am. Chem. Soc. 1986, 108, 7263. (c) Kuo, L. Y.; Kanatzdis, M. G.; Sabat, M.; Tipton, A. L.; Marks, T. J. J. Am. Chem. SOC. 1991, 113, 9027. Lawrence Berkeley Laboratory. 0002-7863/92/1514-10647$03.00/0 0 1992 American Chemical Society