New Chiral Porphyrins—Syntheses and Molecular Recognition of Amino Acid Esters

Abstract

of these products is clearly demonstrated by their circular dichroism (CD) spectra, which show completely symmetric Cotton effects in the region of the Soret bands. The analogous reaction with 4-nitroisophthaloyl chloride gave, following chromatographic separation, meso-2 and 2/ent-2; the enantiomers could be separated again by HPLC.14] All compounds were characterized by 'H NMR spectroscopy and fast atom bombardment mass spectrometry (FAB-MS).In spite of the slight difference between the bridging positions of 1 (para) and 2 (mefa), the topological structures of these porphyrins were expected to be quite different; the angles between planes of the porphyrin and the bridging benzene units in 1 and 2 are predicted by calculations to be approximately 0" and 70-80", respectively (see Fig. 2 ).I5ISynthetic chiral porphyrins have attracted much interest as model compounds for the chiral environments of heme proteins."' We report herein a new synthetic route to chiral porphyrins and their chiral recognition behavior. Since the required synthetic building blocks are achiral atropisomeric tetraarylporphyrins with ortho-substituted phenyl groups and simple bridging reagents, the route is suitable for the preparation of a series of chiral porphyrins for the systematic investigation of molecular recognition properties. Our synthetic scheme is based on the following strategy (Fig. 1). X = NH2 meso-1 l/ent-1 NO. 2 = CONH C I 0 0 Fig. 1. Schematic representation of the synthesis of chiral porphyrins When the a,a,P$ atropisomers of tetraarylporphyrins are doubly bridged with an unsymmetric, difunctionalized reagent, a mixture of a meso porphyrin and a pair of enantiomeric porphyrins with a C, symmetry axis parallel to the porphyrin plane may result,['] which may be separated by chromatography. For example, the reaction of a,a,P$tetrakis(orfho-aminophenyl) porphyrin with nitroterephthaloloyl chloride in T H F gave two doubly bridged porphyrins, meso-1 and llent-1, which could be purified by silica gel c h r~m a t o g r a p h y .~~~ The product with the larger R, value on a silica gel TLC plate was further resolved into the enantiomers 1 and ent-1 on a chiral HPLC column. The chirality Telefdx: Int. code +(75)753-4979 e c Fig. 2. Ball-and-stick molecular models of one each of the sets of enantiomers lien!-1 (left) and 2/ent-2 (right) (see ref. [5]).We attempted to evaluate the chiral recognition abilities of 1 and 2 by determining the association constants of the adducts formed by their Zn complexes and amino acid methyl esters.[61 Titration experiments indicate that various types of amino acid methyl esters form 1 : 1 complexes with 1-Zn and 2-Zn (Table 1). The following interesting aspects of the molecular recognition are clear: a) coordination of the amino acid to meso-1-Zn is hindered significantly compared with that to TPP-Zn, by the benzene bridge; b) in contrast, meso-2-Zn shows a high affinity for amino acids, while the affinity for corresponding simple amines is low; c) the chiral porphyrins 2 and ent-2 show significant c...

Towards a general model for protein–substrate stereoselectivity

“…However, the basic idea of a three‐point interaction continues to be well accepted (Davankov 1997; Pirkle 1997; Copeland 2000; Ahn et al 2001), and explanations similar to the TPA model have been proposed for a variety of stereoselective receptors. These include enzymatic systems (Fersht 1999; Copeland 2000), H‐2 receptors for histamine (Nederkoorn et al 1996), ligand binding to chiral porphyrins (Kuroda et al 1993), taste receptors for sweetness (Shallenberger and Acree 1967; Suami and Hough 1993), and inclusion complexes in cyclodextrins (Ahn et al 2001). The three‐point interaction model is also often cited to explain the mechanisms behind chromatographic enantioresolutions and to design chiral stationary phases and mobile phases for use in chromatography (Dalgliesh 1952; Davankov and Kurganov 1983; Pirkle et al 1983; Nesterenko et al 1994; Morris et al 1996; Vidyasankar et al 1997).…”

“…land 2000), H-2 receptors for histamine (Nederkoorn et al 1996), ligand binding to chiral porphyrins (Kuroda et al 1993), taste receptors for sweetness (Shallenberger and Acree 1967;Suami and Hough 1993), and inclusion complexes in cyclodextrins (Ahn et al 2001). The three-point interaction model is also often cited to explain the mechanisms behind chromatographic enantioresolutions and to design chiral stationary phases and mobile phases for use in chromatography (Dalgliesh 1952;Davankov and Kurganov 1983;Pirkle et al 1983;Nesterenko et al 1994;Morris et al 1996;Vidyasankar et al 1997).…”

Recognition and Sensing of Chiral Organic Molecules by Chiral Porphyrinoids: A Review

“…The pioneering research concerning the chiral recognition of amino acids and corresponding methyl ester derivatives was from Professor Y. Kuroda's group. In fact, between 1993 and 1995, they reported a systematic synthesis of several chiral porphyrinoids to discriminate amino acid methyl esters (Figure 1a-d, I-IV) [55][56][57][58]. In fact, in amino acids, both amino and carboxyl moieties are expected to behave as sites for hydrogen bonding and electrostatic interactions (Figure 1e), whilst the α-R group may form further binding sites (i.e., van der Waals forces, hydrophobic interactions, steric hindrance).…”

“…Nevertheless, if the host system contains a metal ion, a coordination interaction may occur between the guest amino acid and the host system. As a consequence, Kuroda et al, designed Zinc(II)-porphyrin derivatives having two (Figure 1c, III) or three (Figure 1d, IV) recognition elements (i.e., metal coordination, hydrogen bond donor, and hydrogen bond acceptor-or steric repulsion groups) in order to realize a convergent chiral recognition pocket (Figure 1f) [55][56][57][58]. In particular, chiral doubly bridged free-base tetraarylporphyrins (Figure 1a,b I-II), chiral Zinc(II) porphyrins with three arms (5, 10, 15-meso positions, III) and Zinc(II) with two functional arms (5, 15-meso positions, IV) were synthesized as racemic mixtures and resolved by chiral HPLC.…”

Biological chiral recognition: The substrate's perspective

“…7 -10 As Davankov points out, 7 models that feature two points of attachment 4 also require a third point of interaction to explain chiral recognition. The TPI model has been accepted for biological systems like enzymes 9,11 and receptors, 12 -14 chemical systems such as cyclodextrins, 10 chiral porphyrins, 15 and chromatographic chiral stationary phases and mobile phases. 16 -21 On the other hand, there has also been much controversy over the TPI model, 7,8,22,23 and alternative scenarios have been proposed.…”