Shape-Selective Discrimination of Small Organic Molecules

Abstract

Over the past few decades there has been remarkable progress in the synthesis of molecular scaffolds based on superstructured porphyrins.1 A number of these modified porphyrins have been synthesized to mimic various aspects of the enzymatic functions of heme proteins, especially oxygen binding (myoglobin and hemoglobin), and substrate oxidation (cytochrome P-450).1,2 The notable property of many heme proteins is their remarkable substrate selectivity; the development of highly regioselective synthetic catalysts, however, is still at an early stage. Discrimination of one site on a molecule from another and distinguishing among many similar molecules presents a difficult and important challenge to both industrial and biological chemistry.3 Although the axial ligation properties of simple synthetic metalloporphyrins are well documented in literature,4 size and shape control of ligation to peripherally modified metalloporphyrins has been largely unexplored, with few notable exceptions, where only limited selectivities have been observed.5 We report here the synthesis, characterization, and remarkable shape-selective ligation of silyl ether-metalloporphyrin scaffolds derived from the reaction of 5,10,15,20-tetrakis(2′,6′-dihydroxyphenyl)porphyrinatozinc(II) with tert-butyldimethylsilyl chloride, whereby the two faces of the Zn(II) porphyrin were protected with six, seven, or eight siloxyl groups. This results in a set of three porphyrins of nearly similar electronics but with different steric encumbrance around the central metal atom present in the porphyrin. Ligation to Zn by classes of different sized ligands reveals shape selectivities as large as 107. A family of siloxyl-substituted bis-pocket porphyrins were prepared according to the process in Scheme 1.6 Zn[(OH)6PP] and Zn[(OH)8PP] were obtained5a from demethylation7 of corresponding free base methoxy compounds followed by zinc(II) insertion. The methoxy porphyrins were synthesized by acid catalyzed condensation of pyrrole with respective benzaldehydes following Lindsey procedures.8 Metalation was done in methanol with Zn(O2CCH3)2. The tert-butyldimethylsilyl groups were incorporated into the metalloporphyrin by stirring a DMF solution of hydroxyporphyrin complex with TBDMSiCl in the presence of imidazole.9 The octa (Zn(Si8PP)), hepta (Zn(Si7OHPP)), and hexa (Zn(Si6PP)) silyl ether porphyrins were obtained from Zn[(OH)8PP] and Zn[(OH)6PP], respectively. The compounds were purified by silica gel column chromatography and fully characterized by UV-visible, 1H NMR, HPLC, and MALDI-TOF MS. The size and shape selectivities of the binding sites of these bis-pocket Zn silyl ether porphyrins were probed using the axial ligation of various nitrogenous bases of different shapes and sizes in toluene at 25 °C. Zn(II) porphyrins were chosen for this study because, in solution, they generally bind only a single axial ligand. Successive addition of ligand to the porphyrin solutions caused a red-shift of the Soret band typical of coordination to zinc porphyrin complexes. There is no evidence from the electronic spectra of these porphyrins for significant distortions of the electronic structure of the porphyrin. The binding constants (Keq) and binding composition (always 1:1) were evaluated using standard procedures.10 The Keq values of the silyl ether porphyrins with nitrogenous bases of different classes are compared with the sterically undemanding Zn(TPP) in Figure 1. It is worth noting the parallel between shape selectivity in these equilibrium measurements and prior kinetically controlled epoxidation and hydroxylation.2,11 While direct comparisons are not yet available, the selectivity for equilibrated ligation appears to be substantially larger than that for irreversible oxidations of similarly shaped substrates. The binding constants of silyl ether porphyrins are remarkably sensitive to the shape and size of the substrates relative to Zn(TPP) (Figure 1). The binding constants of different amines could be controlled over a range of 101 to 107 relative to Zn(TPP). We believe that these selectivities originate from strong steric repulsions created by the methyl groups of the tert-butyldimethylsiloxyl substituents. The steric congestion caused by these bulky silyl ether groups is pronounced eVen for linear amines and small cyclic amines (e.g., azetidine and pyrrolidine). There are very large differences in Keq for porphyrins having three versus four silyl ether groups on each face (e.g., hexavs