GLAM/Case studies/Absolute confiuguration by optical activity
'ABSOLUTE CONFIGURATION BY OPTICAL ACTIVITY' An absolute configuration refers to the spatial arrangement of the atoms of a chiral molecular entity (or group) and its stereochemical description e.g. R or S, referring to Rectus, or Sinister, respectively. The determine of the absolute spatial relationship (the chirality or handedness) of the atoms in a dissymmetric coordination compound is a problem that has intrigued inorganic chemists from the days of Warner.the later has none of the physical method now available to determine absolute configuration of dissymmetric complexes. AC for a chiral molecule or complexes (or dissymmetric complexes) are most often obtained by X-ray crystallography. Bijovit was first use X-ray diffraction method to determine the absolute configuration of sodium rubidium d-tartrate.after that the method was applied on {(+)- [Co(en)3]Cl3}.NaCl.6H2O and it was found that (+)- [Co(en)3]3+ ion had the ʌ configuration and the enantiomer of same complex had ∆ configuration. Therefore it was now possible to use this complex as standard to determining the absolute configuration of other cobalt complexes by using Optical Rotatory Dispersion (ORD) and Circular Dichroism (CD). Optical Rotatory Dispersion (ORD) and Circular Dichroism (CD).are very use full to determine the absolute configuration of the complexes and also useful to determine the enantiomer of chiral complexes. Complexes which have similar structure give similar Optical Rotatory Dispersion ORD / Circular Dichroism (CD) spectra, provided that they have same absolute configuration.
Configuration by X-ray diffraction method Max von Laue (1912) suggested that X-rays might be diffracted while passing through a crystal where it acts as a three dimensional diffraction grating and produce interference effect. He realized that the wavelength of X-ray are comparable to the separation of lattice planes (interatomic distances is of the order of 10-8 cm). Laue’s suggestion was confirmed immediately by W.Friedrich and P.Knipping and has grown since then into a technique of extraordinary power. The resolved X Ray diffraction technique make use of synchrotron sources which can emit intense poly chromatic pulses of X-ray radiation with pulse widths varying from 100 ps to 200 ps.The technique in the millisecond can identify a number of structural change that follow electronic excitation of the chromatophore with a ;laser pulse i.e. isomerization, ejection, protonation of the exposed chromophore and a number of amino acids motion. AC for a chiral molecule or complexes (or dissymmetric complexes) are most often obtained by X-ray crystallography. Bijovit was first use X-ray diffraction method to determine the absolute configuration of sodium rubidium d-tartrate.after that the method was applied on {(+)- [Co(en)3]Cl3}.NaCl.6H2O and it was found that (+)- [Co(en)3]3+ ion had the ʌ configuration and the enantiomer of same complex had ∆ configuration. Busing this (+)- [Co(en)3]3+ ion’s X-ray data as a standard and we can determine the absolute configuration of other cobalt complexes by optical activity i.e. (on the basis of ORD/CD).
Determination Of Absolute Configuration By Using Optical Rotatory Dispersion (ORD)
Optical rotatory dispersion is the variation in the optical rotation of a substance with a change in the wavelength of light. Optical rotatory dispersion can be used to find the absolute configuration of metal complexes. For example, when plane-polarized white light from an overhead projector is passed through a cylinder of sucrose solution, a spiral rainbow is observer perpendicular to the cylinder. “When white light passes through a polarizer, the extent of rotation of light depends on its wavelength. Short wavelengths are rotated more than longer wavelengths, per unit of distance. Because the wavelength of light determines its color, the variation of color with distance through the tube is observed.] This dependence of specific rotation on wavelength is called optical rotatory dispersion.”
ORD involves in measuring the variation of optical rotation with wavelength. if the complex is levorotatory, the ORD curve falls to a minimum , rise rapidly to
a maximum and then falls slowly.
If the complex is dextrorotatory the ORD curve rising first to maximum then falling. Levorotatory curve present the positive cotton effect and dextrorotatory curve of ORD represent negative cotton effect. the ORD curve is useful to determine the absolute configuration— Absolute configuration of enantiomers of tris(ethylenediamine)cobalt (iii), tri(alaminato)cobalt (iii) and bis(ethylenediamine)glutamate cobalt(iii)are known from X-ray diffraction technique. It is found that three ʌ-(+)-enantiomers or ʌ -(D)-enantiomers of these complexes have similar ORD spectra. On the basis of ʌ -configuration, these complexes can be assigned to any known configuration in the absence of X-ray data simply on the basis of the similarity of ORD spectra. For ORD spectrum to be instantly recognizable, no other absorption must be nearby. The ORD spectra of ʌ -[Co(en)3]3+, ʌ -[Co(S-ala)3]3+, and ʌ -[Co(en)2(S-glu)]3+ are shown in figure 2. All these complexes represent positive Cotton effect. (Where en refers to ethylenediamine, S-ala refers to the anion of S-(L)-alanine and S-glu refers to the dianion of S-(L)-glutamic acid. All of these complexes have the ʌ or D configuration.)
Figure 2(a)
Figure 2(b)
Figure 2(c)
Although ORD was used extensively at one time because of simpler instrumentation, circular dichroism (CD) is currently much more useful.
Determination of AC using circular dichroism CD Circular dichroism involving circularly polarized light that is the differential absorption of left circularly polarized light εl and right circularly polarized light εr (εl- εr).this phenomenon was discovered by Jean-Baptiste Boit, Augustin Fresnel and Aime cotton in the first half of the 19th century. It is exhibited in the absorption band of optically active chiral complexes and molecules. Complexes having same sigh of CD for a given absorption band will have the same absolute configuration , The absolute configuration of [Co(en)3]3+ is shown in figure given below. The CD spectrum of [Co(en)3]3+ suggest that ʌ - [Co(en)3]3+ isomer shows positive deflections, however ∆-[Co(en)3]3+ isomer shows negative deflections in CD spectrum which also corresponds to the sign of Cotton effect. The CD spectrum of [Co(en)3]3+ also shows the presence of another absorption band at ~24×10-3 cm-1 that is not obvious from the absorption spectrum.
Figure 3(a)
this curve show absorption spectra of circular dichroism of optically active metal complexes.
Figure 3(b) Tris(aminoacido)cobalt complexes were prepared using amino acids. CD spectra of these complexes illustrate the application of circular dichroism for the determination of configuration. If three glycinate ligands are bound to a metal ion, two diastereomers: fac and mer are possible and each of these will have an enantiomer shown in fig given below.
Figure 4 However, if a substituted amino acid such as alanine (R-alanine or S-alanine) is used, complex can still exist as two geometrical isomers both of which are chiral, i.e. fac and mer. The arrangement of ligands about metal ion can result in ʌ or∆ chirality. However, right-handed fac isomer is not enantiomeric with the left-handed fac isomer. For example, the use of S-alanine can give the fac ʌ has isomer shown in figure. A mirror image of this compound cannot be generated with S-alanine because the enantiomer necessarily contains R-alanine. Therefore, fac ∆ isomer is a diastereomer of fac ʌ. This is the same case with mer isomers. The net result is that, if glycine is used while fac and mer isomers have an enantiomeric partner, however, an optically active amino acid will give a diastereoisomer for each chirality of each fac or mer isomer. All the four isomers shown in figure 5 and 6 are diastereomers, easily separable from one another under achiral conditions. Each one of them is having different physical properties.
Figure 5
Figure 6 The fac and mer isomers show distinct spectroscopic properties from one another. The fac isomers give rise to similar UV-visible spectra (Figure 7); similarly mer isomers also give similar UV-visible spectra. The absolute configuration of the optically pure alanine complexes can be assigned by comparing their CD spectra to those for optically pure [Co(en)3]3+. The absorption and CD spectra for the four diastereomers of [Co(S-alaninate)3] are shown in figure. The sign of the Cotton effect for the lowest energy CD band of the fac-(+) and mer-(+) isomers is positive just as it is for ʌ -(+)-[Co (en)3]3+. This result strongly suggests that these complexes have the same absolute configuration, ʌ. The negative sign of the Cotton effect for the lowest energy CD band of the fac-(-) and mer-(-) isomers suggests that they have an absolute configuration opposite to that for the (+)- isomers. This result suggests that these complexes have the same absolute configuration, ∆. It should be noted that CD curves for the (+) and (-) isomers are not exactly mirror images of one another. This is due to the fact that, while complexes have opposite absolute configurations based on the positioning of chelate rings, they are in fact diastereomers as mentioned above, this arises because only S-alaninate was used as a ligand .
Figure 7
Assignment of the Ligand Conformation using Circular Dichroism (CD)
As we are aware that in tris(chelate) octahedral complexes, dissymmetry can also be generated by using dissymmetric ligand. For example, the gauche conformation of ethylenediamine is dissymmetric (Figure 8) and could be resolved were it not for the almost complete absence of an energy barrier preventing racemization. Attachment of the chelate ligand to a metal retains the chirality of the gauche form, but the two enantiomers can still interconvert through a planer conformation at a very low energy, similar to the interconversion of organic ring systems. Thus, although it is possible to have two enantiomers of a complex such as [Co(NH3)4(en)]3+, but it is impossible to isolate them due to rapid interconversion of the ring conformers. In this case, two enantiomers of a complex are possible due to δ or λ chirality of the ethylenediamine-metal ring. Figure 8 If two or more rings are present in one complex, they can interact with each other and certain conformations might be expected to be stabilized as a result of possible decrease in the interatomic repulsions. For example, consider a square planer complex containing two ethylenediamine rings. It can assume three possible structures; Mδλ, Mλλ and Mδλ (or Mδλ). The first two lack a plane of symmetry, but Mδλ is a meso form. Corey and Bailer showed that Mδδ and Mλλ are more stable as compared to Mδλ (meso). This is due to the fact that meso compound has unfavorable H-H interactions of axial-axial and equatorial-equatorial type between the two chelate rings (Figure 9). Figure 9 Similarly for an octahedral tris(chelate) complex we might expect to have Mδδδ, Mδλλ, Mδδλ and Mλλλ forms. All these forms are optically active, so there can be in total eight isomers, but only two isomers have been isolated. This stereoselectivity is most easily followed by using a chiral ligand such as propylenediamine (pn), CH3CH(NH2)CH2NH2. The configuration of the (+) enantiomer of the ligand has been shown to be S (Figure 10). If the molecule in this configuration is attached to a metal, two conformations are possible (Figure 11). The conformation with the CH3 group in an equatorial position (i.e., δ) is more likely as compared to one with the CH3 group in axial position (i.e., λ). Note that the S-pn δ conformation is the mirror image of the R-pn λ conformation (Figure 12); therefore, if the diamine or R configuration is used, the conformation of greater stability should be λ. Figure 10
Figure 11
Figure 12 If R-pn is treated with cobalt(III) sulfate and oxygen, two isomers of empirical formula [Co (R-pn)3]3+ are isolated and they are not enantiomeric to one another. Instead of having equal and opposite rotations as expected for enantiomers, they have specific rotation of - 24˚and +214˚. S-pn also gives two diastereoisomers, but these have rotation of +24˚ and -214˚. It is clear that R-pn and S-pn have given two pairs of enantiomers, one pair having R- or S- ligands with specific rotation ±24˚and another pair, again with R- or S- ligands with specific rotation ±214˚. An X-ray analysis of the (–)-[Co (S-pn)3]3+ isomer indicates that
1. All the three chelate methyl groups are cis to one another 2. The absolute configuration is ∆ 3. The pn chelate rings are in the expected δ conformation.
Complex configuration ligand conformation specific rotation[α] [Co(S-pn)3]I3H2O ʌ δδδ +24˚ [Co(R-pn)3]I3H2O ∆ λλλ - 24˚ [Co(S-pn)3]I3H2O ∆ δδδ - 214˚ [Co(R-pn)3]I3H2O ʌ λλλ +214˚
Therefore, assuming that methyl groups are cis to one another in all of the complexes, the enantiomeric (+)-[Co(R-pn)3]3+ must have ʌ configuration with rings arranged in λ conformation. Likewise, the configurations and ring conformations of the remaining isomers are given in table 1. The authenticity of this analysis can be confirmed by the CD spectrum of (+)-[Co (S-pn)3]3+, which is similar to that of ʌ-(+)-[Co (en)3]3+ (Figure 13); in contrast, the CD spectrum of (-)-[Co (S-pn)3]3+, is opposite to that of ʌ (+)-[Co(en)3]3+.
Figure 13
Summary In this module, we discussed that
The absolute configuration in dissymmetric complexes is determine by X-ray crystallography. Bijovit was first use X-ray diffraction method and it was found that (+)- [Co(en)3]3+ ion had the ʌ configuration and the enantiomer of same complex had ∆ configuration This (+)- [Co(en)3]3+ complex used as standard to determining the absolute configuration ( in the absence X-ray crystallography )of other cobalt complexes by using Optical Rotatory Dispersion (ORD) and Circular Dichroism (CD). CD and ORD spectra can be used to identify two enantiomers of a chiral complex. Compounds with similar structures give similar ORD/CD spectra if they have the same absolute configuration. The essence of the method is to recognize that molecules of identical configuration should have the same Cotton effect for electronic transitions of the same origin, whereas enantiomers will have mirror image Cotton effects. If two or more rings of the ligands are present in one complex, they can interact with each other and certain conformations might be expected to be stabilized as a result of possible reductions in interatomic repulsions.