On this page, we will briefly summarize features of exciton-coupled circular dichroism (ECCD) pertinent to our studies; more thorough treatments of the spectroscopy can be found elsewhere [1-3]. We will then provide a brief review of the role that ECCD has played in our laboratory's studies of stereodynamic coordination complexes.
Two chromophores present in a molecule in close proximity to one another may experience interaction of the electronic transitions, resulting in differentiation of the energies of the transitions (Figure 1). In such a case, two distinct UV-vis bands may, in principle, be observed, with the difference in energy corresponding to the difference between the two absorption maxima (lambda-max). In practice, UV-vis spectra are broad and two distinct bands are seldom observed. However, in CD spectra, the two coupled absorbances display Cotton effects with opposite signs, resulting in sigmoidal shaped curves. Such exciton-coupled CD spectra are characterized by the shape of the curve, the large amplitude of the spectrum, and the correspondence of the null in the CD spectrum with the lambda-max from the UV-vis spectrum 1, 3, 4. Few other spectroscopic signals report structural aspects of molecular conformation so dramatically as ECCD. By this feature, ECCD can be used to assign absolute configurations of a variety of organic molecules, since in many cases the conformation of the molecule is known and related to the absolute sense of chirality of the molecule.
Figure 1. Exciton interactions give rise to split CD spectra.
Our interest has been drawn to the opportunity to modulate the intensity or sign of the ECCD couplet by coordination chemistry, molecular recognition, or design of compounds with triggered conformations . The amplitude (A, Figure 1) of the ECCD spectrum depends on several factors among which include the strength of the electronic transition, the distance between the chromophores, and the angle between the vectors representing the coupled electronic transition dipoles [1, 3, 4]. Each of these factors is amenable to modulation. In particular, the distance and angle between the chromophores are dependent upon molecular conformation.
Metal complexes of tris(pyridylmethyl)amine (TPA) have been studied extensively . This tripodal ligand, which adopts two rapidly interconverting, enantiomeric conformations (Figure 2, structures 1 and 2) when bound to Cu(II) or Zn(II), has provided the scaffold upon which a variety of stereodynamic metal complexes have been developed . Incorporation of a single chiral center on one of the arms of TPA creates an analogous pair of conformational diastereomers, as in structures 3 and 4 of Figure 2. The pyridines adopt a propeller-like orientation, the direction of which is dictated by the methyl substituent, with the metal and the tertiary nitrogen forming the axis. In this case, the equilibrium is shifted toward the left-handed propeller because the methyl substituent points away from the pyridyl group .
Figure 2: a) Conformational enantiomerism in tripodal ligand complexes of Cu(II), S = solvent or counter ion; b) Incorporation of a single chiral carbon center results in conformational diastereomers.
When pyridines are replaced by quinolines, these complexes give strong ECCD spectra [7, 9]. Figure 3 illustrates one compound that as a free ligand exists in many conformations and therefore gives a weak CD spectrum. Upon complexation with Zn(II), the ligand wraps around the metal ion, and the quinoline chromophores are fixed in an orientation that gives rise to a strong ECCD couplet. The sign of the ECCD couplet reveals the absolute sense of orientation of the quinoline moieties, and therefore the handedness of the propeller. Since the propeller configuration depends on the absolute configuration of the chiral carbon center, the latter can be assigned from the sign of the ECCD couplet. An X-ray crystallographic structure of the Zn(II) complex (Chem-3D structure from X-ray coordinates shown with two views in Figure 3) corroborated the solution CD spectrum. Since then, many other crystallographic structures of similar complexes coupled with solution CD studies have set our understanding of conformations in pyridyl and quinoline tripodal ligand complexes on firm ground . Zinc(II) and Cu(II) complexes give similar CD spectra because they typically form 5-coordinate, trigonal bipyramidal structures with these tripod ligands. Octahedral metals, such as Cd(II) and Fe(II), may not give the proper orientation for ECCD and therefore may not show strong CD spectra as shown in Figure 3 .
Figure 3. The free ligand may obtain many conformations; complexation to Cu(II) causes the ligand to wrap around the metal ion, adopting a propeller shape, and orienting the quinoline chromophores for ECCD. CD spectra of ligand and Cu(II), Zn(II), CD(II), and Fe(II) complexes, micromolar solutions in water; only Cu(II) and Zn(II) complexes give ECCD spectra.
We have reported conformational analysis of additional tripodal metal ion complexes of ligands such as those shown in Figure 4 using solution, solid state, and computational methods. Various primary amines were alkylated with two chromophores, and complexation to Cu(II) created a conformationally defined, asymmetric species featuring a helical configuration dictated by the absolute configuration of the chiral center. Chiral ligands displayed an M (lambda) propeller-like twist when the carbon center was of R configuration and a P (delta) twist for the S carbon center. Several of these compounds were also examined for their ability to induce helicity in liquid crystal nematic phase. An intense difference between the free ligands and the copper complexes and copper complexed in different oxidation states and with different center ions suggests possible use liquid crystal display devices . Molecular recognition of various anions was observable in both CD spectra and helical inducing power determinations.
Figure 4: Tripodal ligands with various alkyl groups and chromophores.
One possible application of this research is in the assignment of absolute configurations of chiral primary amines by analysis of ECCD spectra of the derivatives. Derivatization methods with quinoline have shown to work very well with amino acids and alcohols [11, 13, 14]. A great advantage of the derivatization method is the concurrent assessment of enantiopurity because there is a linear agreement between CD intensity and ee. Figure 5 shows a typical ECCD spectrum for a quinoline derivatized amino alcohol, S-methioninol, which demonstrates that the negative couplet corresponds to the S-isomer and the positive couplet to the R-isomer . Other, complimentary methods have also been reported for assignment of amine absolute configuration by ECCD [16, 17].
Figure 5: ECCD spectra of S- and R-isomers of Cu(II)LCl.
Another area that we have examined is the modulation of ECCD amplitude and sign triggered by redox chemistry [18, 19]. Molecular switching devices can be applied in information technology, where chemical devices rely on assuming on/off states. Helical supramolecular structures, macromolecules, and nanostructures derived from natural or synthetic building blocks that are capable of inverting their handedness upon physical stimulation offer insights into molecular structure and interactions as well as opportunities for device development. The ability to control helicity of supramolecular structures could lead to practical applications in the polymer, electronics, and pharmaceutical industries .
Figure 6 depicts the exciton coupled circular dichroism and UV spectra of the Cu(II) and Cu(I) complexes of S-methionine derivative Cu(L)ClO4 in methanol . In this figure, the complexes give ECCD spectra that are nearly mirror images of each other. The Cu(II) complex involves coordination by the ligand via three nitrogen atoms and an oxygen atom. For the (S)-enantiomer, this results in a negative chiral orientation of the chromophores, and gives rise to a (-)-couplet in the ECCD spectrum. The Cu(I) complex displays coordination to the alkyl sulfide arm instead of the carboxyl group, resulting in the inversion of the twist of the molecule, and yielding a (+)-couplet in the ECCD spectrum. The mirror image CD spectrum for the redox isomer arises from inversion of the configuration of the two chromophores, which invert as a result of the pivot of the chiral arm of the tripod complex. Similar electron-driven chiral inversion was also observed with S-methyl cysteine and methioninol derivatives [21, 22]. The rate of switching was examined recently by scanning electrochemical microscopy and stopped flow circular dichroism .
Figure 6: Redox driven helix inversion. a) Ligand reorganization that occurs upon redox reaction (X = solvent or counter ion); b) : CD and UV spectra of Cu(I) and Cu(II) complexes.
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