Exciton chirality

Simonyi M, Bikadi Z, Zsila F, and Deli J. 2003. Supramolecular exciton chirality of carotenoid aggregates. Chirality 15(8) 680-698. 

The configuration of the 4R,5R-dihydrodiol was established by application of the exciton chirality method (6). To minimize undesired interactions between the electric transition dipoles of the two j>-N,N-dimethylaminobenzoate chromophores and the dihydrodiol chromo-phore, a 4,5-dihydrodiol enantiomer was first reduced to 1,2,3,3a,4,5,7,8,9,10-decahydro and 4,5,7,8,9,10,11,12-octahydro derivatives (6). We found that it is not necessary to reduce the chrysene chromophore of a BaP 4,5-dihydrodiol enantiomer (Figure 2). Similarly, the absolute configurations of the K-region dihydrodiol enantiomers of BA (7), 7-bromo-BA (8), 7-fluoro-BA (9), 7-methyl-BA (10). and 7,12-dime thy 1-BA (DMBA) (7 ) can also be determined by the exciton chirality method without further reduction. 

The absolute configuration of the 7,8-dihydrodiol metabolite was also established to be 7R,8R by the exciton chirality method (11.12), Our result (Figure 2) is in agreement with those reported earlier (11.12). 

The absolute configuration of the 9,10-dihydrodiol metabolite was established to be 9R,10R both by nuclear magnetic resonance spectroscopy and by the structures of the hydrolysis products formed from the svn and anti 9,10-dihydrodio 1-7,8-epoxides which were synthesized from the same 9,10-dihydrodiol enantiomer (13). The absolute configuration of a BaP trans-9.10-dihvdrodiol enantiomer, after conversion to a tetrahydro product, can also be determined by the exciton chirality method (Figure 2) (19.20). 

Figure 2. The exciton chirality CD spectra of bis-p-N,N-dimethyl-aminobenzoyl derivatives of BaP 7.8.9.lO-tetrahvdro-trans-7.8-diol (1.0 A fc/ml, derived from BaP trans-7.8-dihvdrodiol metabolite),...

We have tried to express the results of Weigang s treatment in pictorial form (Scheme 6), applying the language of the exciton chirality rulesld to the coupling of the chromophore transition dipole moments with those induced in the nearby bonds. These are regarded... 

For a system containing two chromophores i and j, the exciton chirality (positive or negative) governing the sign and amplitude of the split Cotton effect can be theoretically defined as below59 ... 

Figure 1-17. Exciton chirality of acyclic allylic benzoates and the sign of the predicted benzoate Cotton effects. The thick line denotes the electric transition moment of the benzoate group. Reprinted with permission by Am. Chem. Soc., Ref. 61. 

Harada N, Nakanishi K, Exciton chirality method and its application to configurational and conformational studies of natural products, Accounts Chem Res 5 257-263, 1972. 

The Cotton effects may be classified into three types168 those arising from chirally perturbed local achiral chromophores (ketones, /i.y-unsaturated ketones, double bonds, benzoates, aromatic compounds) those arising from inherently achiral chromophores, such as conjugated dienes or a,/3-unsaturated ketones those arising from interaction of the various electric transition moments when two or more chromophores which are chirally disposed are positioned nearby in space, intra- or intermolecularly (exciton chirality method)169. 

A useful method for the establishment of the absolute configurations of chiral primary amines involves formation of their salicylidene derivatives and application the salicylidcnamino chirality rule 172. Other procedures for primary amines are based on, either the CD of their V-(2,4-diniirophenylsulf enyl)- V-(4-methylphenylsulfonyl) derivatives as described in Section 4.3.4.I.5.251, or on the exciton chirality method313. 

Recently, a method was developed which allows assignment of the configuration around a secondary carbinol center combining kinetic resolution and the exciton chirality CD method241 (see Section 4.3.4.1.4., p 458). 

In special cases of nonracemic compounds, both relative and absolute configuration can be determined by means of circular dichroism. Thus, the relative and absolute configurations of acyclic 1.2-, 1,2,3-, 1,2,3,4-, and 1,2,3,4,5-polyols can be determined by the bichromophoric exciton chirality method after a two-step derivatization [primary and secondary hydroxy groups are selectively esterified with 9-anthroyl chloride (2) and ( )-3-(4-methoxyphenyl)-2-propenoyl chloride (4), respectively] and comparison of the CD curves with references curves265. 

For example, compounds 5 obtained from 1,2,3-triols of type 1 provide CD spectra which distinguish characteristically and predictably between stereoisomers (bichromophoric exciton chirality method). Thus, relative and absolute configuration of such 1,2,3-triols can be deduced from a single measurement180. 

The following discussion is divided into three subsections the ketone chromophore (Section 4.4,1.1.), for which configurational assignments are based on the effect of ring dissymmetry and substitution pattern on the rotatory power of the n-rt transition. For conjugated chro-mophores (Section 4.4.1.2.) it is both the helicity of the chromophore and the vicinal substituent effect that determines the rotatory power of the 71-71 transition. Finally, the versatile stereochemical method, exciton chirality method (Section 4.4.2.), is based on the chiral interaction between the electric dipoles of the allowed transitions in two or more chromophores. 

For non-coplanar electric transition dipole moments pi0a and pj0a of the two chromophores at Rjj interchromophoric distance the exciton chirality is nonzero and defined by ... 

Figure 13. Definition of exciton chirality. Summation of the two Cotton effects (broken lines) separated by Davydov splitting A). gives the curves shown in solid lines. Adapted from N. Harada, K. Nakanishi. Circular Dichroic Spectroscopy - Exciton Coupling in Organic Stereochemistry, University Science Books. Mill Valley, California. 1983...

Many chromophores are suitable for use in the exciton chirality method. One of the features required for such a chromophore is its planarity or near-planarity. Nonplanar (inherently dissymmetric) chromophores would contribute to the CD spectra by other mechanisms. The other limiting factor is the position of the transition in the spectral region studied. For example, the 1B transition in the alkyl-substituted benzene chromophore appears near the short-wavelength recording limit around 200 nm, making its use in the exciton chirality method less attractive. Furthermore, the direction of polarization of the lB transition in alkyl-substituted benzene derivatives is not readily determined. In such cases calculation of the rotatory strength is more reliable than qualitative analysis. 

Table 7 lists some of the most common chromophores used in stereochemical studies by the exciton chirality method. 

Table 7. Chromophores and Polarization of Transitions Useful for Application in the Exciton Chirality Method...

The power of the exciton chirality method lies in its applicability to molecules having functional groups which are not chromophores in the usual sense (such as hydroxy, amino or thiol groups), but can be converted to a chromophoric derivative, such as an unsaturated or aromatic acyl derivative. This procedure is extremely useful for the determination of the absolute configuration of products of stereoselective synthesis having a hydroxy, amino or thiol group at the stereogenic center. 

The dibenzoate chirality rule 155, 156 extends the application of the exciton chirality method to molecules containing no suitable chromophore, but, rather two hydroxy groups which can be converted to benzoates or cinnamates. For example, the dibenzoate 1, obtained by benzoy-lation of the ra-diol, from microbial oxidation of ethylbenzene, displays a negative exciton Cotton effect and is hence assigned the 1 S.2R configuration157. 

The absolute configuration of a molecule bearing three or more hydroxy groups attached to the acyclic skeleton can also be determined in a nonempirical way through application of the exciton chirality method. The amplitude of the polybenzoate exciton Cotton effect is a sum of amplitudes of Cotton effects of the component pairs of benzoates. This additivity relationship allows characterization of pyranoses through their 4-bromobenzoate exciton Cotton effects168 (Figure 20). 

The pairwise additivity principle when applied to bichromophoric exciton-coupled systems, such as those composed of 4-bromobenzoate (BB) and 4-methoxycinnamate (MC) derivatives of cyclic polyols, yields more information from the CD spectra of complex molecules173. In such systems both degenerate ( homo") interactions, i.e., BB/BB and MC/MC, and nondegenerate ("hetero") interactions, i.e., BB/MC, contribute to the exciton CD spectra. As the homo exciton Cotton effects arc well separated (BB 236/253 nm, MC 287/322 nm) a unique pattern of CD curves is obtained for each derivative of cyclic tri- or tetraol. This method is particularly useful in identification of glycopyranosides174, a procedure essential for microscale structure determination of oligosaccharides by the exciton chirality method175. 

The secondary structure of poly(iV-alkynylamides) is influenced by the position of the chiral center and amide group.The position of the chiral center mainly affects the helical pitch, which becomes short when the chiral center is positioned away from the main chain. The stability of the helical structure is also influenced by the position of the amide group. Based on molecular orbital study, it is concluded that poly(iV-propargylamides) with right-handed helical structure display a plus Cotton effect around 390 nm. This is also confirmed by the exciton chirality method using porphyrin as a chromophore. ... 

In an effort to obtain a salvinorin derivative possessing an oe-diol system which can be transformed into the dibenzoate ester required for the exciton chirality CD method, salvinorin A (1) or B (2) was treated with sodium borohydride in various protic solvents. The products having the la,2a-diol group were obtained in high yield. However, this reduction was accompanied by extensive isomerization at C-8. While mechanistic details for this unexpected observation remain to be established at this time, the isomerization at C-8 appears to be the result of the base-promoted clevage of the C-8/9 bond under the reaction conditions followed by the reclosure to provide the 8-epimer prior to the reduction of the 1-ketone. Furthermore, attempts to obtain the 1,2-dibenzoate derivative of the major reduction product 3 under various benzoylating conditions invariably produced only the 2-monobenzoate. 

Application of the exciton chirality rule has allowed the assignment of configuration (+ )-trans-(4R,5R) to dihydroxy-4,5-dihydrobenzo[a]pyrene (357), a mammalian metabolite of benzo[a]pyrene.217 Thus the prominent enantiomer of the 4,5-dihydrodiol formed from benzo [a] pyrene by rat-liver microsomes has the configuration (4R,5R) in contrast to the earlier report that the configuration was the opposite one.218 Consequently, ( + )-(358) has a (4S,5R) configuration. This epoxide is a better substrate for epoxide hydrolase than its enantiomer and has 1.5-5.5-fold less mutagenic activity as compared to the (—) enantiomer. 

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