Effects of complex formation on vibrational circular dichroism spectra

The determination of absolute configurations of chiral compounds using VCD is performed by comparing measured vibrational circular dichroism (VCD) spectra with calculated spectra. The process is based on two facts: the two enantiomers have rotational strengths of opposite sign, and the absolute configuration of the molecule used in the calculation is known. However, calculations on isolated molecules very often predict VCD intensities of very different magnitude or even different signs compared to the spectra measured in solution. Therefore, we have carefully analyzed what type of changes are induced by complexation of a solvent molecule to a solute. In the theoretical example of benzoyl-benzoic acid (in a particular chiral conformation) hydrogen bonded to the achiral NH3, we distinguish six cases, ranging from no or very small changes in the rotational strengths of solute modes (case A) to changes of sign of rotational strengths (case B), changes in magnitude (case C), nonzero rotational strengths for modes of the achiral solvent ("transfer of chirality", case D), large frequency shifts accompanied by giant enhancements of the IR and VCD intensities of modes involved in hydrogen bonding (case E), and emergence of new peaks (case F). In this work, all of these situations will be discussed and their origin will be elucidated. On the basis of our analysis, we advocate that codes for VCD rotational strength calculation should output for each mode i the angle xi(i) between the electric and magnetic transition dipole moments because only "robust modes" with xi far from 90 degrees should be used for the determination of the absolute configuration.     

Effects of central metal ions on vibrational circular dichroism spectra of tris-(beta-diketonato)metal(III) complexes

Vibrational circular dichroism (VCD) spectra of a series of [M(III)(acac)3] (acac = acetylacetonato; M = Cr, Co, Ru, Rh, Ir, and Al) and [M(III)(acac)2(dbm)] (dbm = dibenzoylmethanato; M = Cr, Co, and Ru) have been investigated experimentally and/or theoretically in order to see the effect of the central metal ion on the vibrational dynamics of ligands. The optical antipodes give the mirror-imaged spectra in the region of 1700-1000 cm(-1). The remarkable effect of the central metal ion is observed experimentally on the VCD peaks due to C-O stretches (1500-1300 cm(-1)) for both [M(III)(acac)3] and [M(III)(acac)2(dbm)]. In the case of Delta-[M(III)(acac)3], for example, the order of frequency of two C-O stretches (E and A2 symmetries) is dependent on the kind of a central metal ion as follows: E (-) > A2 (+) for M = Co, Rh, and Ir, while A2 (+) > E (-) for M = Cr and Ru. In the case of Delta-[M(III)(acac)2(dbm)], the order of frequency of three C-O stretches (A, B, and B symmetries) is as follows: A (-) > B (+) > B (+) for Co(III), B (+) > A (-) > B (-) for Cr(III), and A (-) > B (+) > B (-) for Ru(III). These results imply that the energy levels of C-O stretches are delicately affected by the kind of central metal ion. Since such detailed information is not obtained from the IR spectra alone, the VCD spectrum can probe the effect of the central metal ion on interligand cooperative vibration modes.     

DFT study of vibrational circular dichroism spectra of D-lactic acid-water complexes

This paper presents a discussion of the interaction energies, conformations, vibrational absorption (VA, harmonic and anharmonic) and vibrational circular dichroism (VCD) spectra for conformers of monomeric chiral d(-)-lactic acid and their complexes with water at the DFT(B3LYP)/aug-cc-pVDZ and DFT(B3LYP)/aug-cc-pVTZ levels. A detailed analysis has been performed principally for the two most stable complexes with water, differing by lactic acid conformation. The VCD spectra were found to be sensitive to conformational changes of both free and complexed molecules, and to be especially useful for discriminating between different chiral forms of intermolecular hydrogen bonding complexes. In particular, we show that the VCD modes of an achiral water molecule after complex formation acquire significant rotational strengths whose signs change in line with the geometry of the complex. Using the theoretical prediction, we demonstrate that the VCD technique can be used as a powerful tool for structural investigation of intermolecular interactions of chiral molecules and can yield information complementary to data obtained through other molecular spectroscopy methods.     

Selected deoxyoctanucleotides and their daunomycin complexes: Infrared absorption and vibrational circular dichroism spectra

The infrared absorption (IR) and vibrational circular dichroism (VCD) spectra are reported for six self-complementary deoxyoctanucleotides complexed with the anthracycline drug daunomycin. The oligomers included d(CGCGCGCG)·d(CGCGCGCG), d(CGCATGCG)·d(CGCATGCG) and d(CGCTAGCG)·d(CGCTAGCG), which possess a 5′CGC triplet, and d(CGATATCG)·d(CGATATCG), d(CGTATACG)·d(CGTATACG) and d(CGAATTCG) ·d(CGAATTCG), which have either 5′CGA or 5′CGT triplets. The latter three triplets were said to be favorable intercalation sites for this drug, while the former three were considered to be non-preferred. Changes in the VCD spectra upon drug binding indicate a perturbation of the structure at the base step involving cytosine (Cy) and guanine (Gu), which appears to comprise the daunomycin intercalation site. The VCD spectra also show distinct changes as the drug binds with base sequences that contain 5′CGC triplets compared to those with either 5′CGA or 5′CGT triplets. These differences are attributed to specific binding interactions of the DNA components with the functional groups of the aglycone chromophore and its amino sugar moiety.     

Density functional calculations on electronic circular dichroism spectra of chiral transition metal complexes

Time-dependent density functional theory (TD-DFT) has for the first time been applied to the computation of circular dichroism (CD) spectra of transition metal complexes, and a detailed comparison with experimental spectra has been made. Absorption spectra are also reported. Various Co(III) complexes as well as [Rh(en)(3)](3+) are studied in this work. The resulting simulated CD spectra are generally in good agreement with experimental spectra after corrections for systematic errors in a few of the lowest excitation energies are applied. This allows for an interpretation and assignment of the spectra for the whole experimentally accessible energy range (UV/vis). Solvent effects on the excitations are estimated via inclusion of a continuum solvent model. This significantly improves the computed excitation energies for charge-transfer bands for complexes of charge +3, but has only a small effect on those for neutral or singly charged complexes. The energies of the weak d-to-d transitions of the Co complexes are systematically overestimated due to deficiencies of the density functionals. These errors are much smaller for the 4d metal complex. Taking these systematic errors and the effect of a solvent into consideration, TD-DFT computations are demonstrated to be a reliable tool in order to assist with the assignment and interpretation of CD spectra of chiral transition metal complexes.     

Absolute configuration, predominant conformations, and vibrational circular dichroism spectra of enantiomers of n-butyl tert-butyl sulfoxide

Alkylation of the alpha-carbanion of (R)-(-)-tert-butyl methyl sulfoxide (4) with n-propyl bromide afforded (+)-n-butyl tert-butyl sulfoxide (1) to which the absolute configuration (R) was ascribed. This assignment was confirmed by X-ray analysis of the complex 6 obtained from the enantiomerically pure sulfoxide (-)-1 and mercury chloride. Vibrational absorption and circular dichroism spectra of (+)-1 were measured in CDCl3 solution in the 2000-900 cm(-1) region and compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using the B3LYP/6-31G basis set for different conformers of (R)-1. This comparison indicated also that (+)-1 is of the (R)-configuration.     

Absolute configuration of diterpenoids from Jatropha dioica by vibrational circular dichroism

The absolute configuration of jatropholone A 1 and B 2, including the possibility to observe the vibrational circular dichroism (VCD) capacity to differentiate between two epimeric compounds in the presence of an inherently dissymmetric chromophore, which normally dominates VCD and electronic circular dichroism (ECD) spectra, followed after comparison of their experimental and DFT calculated VCD spectra, allowed us to conclude that although non-local (M/P) chirality generated by atropisomerism dominates over local chirality generated by an (R/S) change, the stereogenic center can confidently be assigned by VCD after DFT calculations. In addition, the absolute configurations of jatrophatrione 3 and citlalitrione 4, a compound proposed as a taxonomic marker for the genus Jatropha, were assigned by contrasting their respective calculated and experimental IR and VCD spectra. The evaluation of Flack and Hooft parameters obtained from the single-crystal X-ray diffraction data of jatropholone B acetate 6, and of 4 independently confirmed the absolute configurations of these molecules.     

Reliability of computed signs and intensities for vibrational circular dichroism spectra

We present in detail a novel measure that improves the reliability of the assignment procedure for vibrational circular dichroism (VCD) spectra extending the useful robustness concept introduced by Nicu and Baerends. This measure enables spectroscopists to single out bands with unreliable VCD intensities that can be disregarded during analysis and determination of absolute configuration. The previously proposed robustness criterion is shown to be gauge dependent and less reliable than the one proposed here.     

Theoretical study on vibrational circular dichroism spectra of tris(acetylacetonato)metal(III) complexes: anharmonic effects and low-lying excited states

The open-shell density functional theory calculations with M06 exchange-correlation functional and all-electron Douglas-Kroll second order scalar relativistic correction were performed to interpret the vibrational circular dichroism (VCD) spectra of four kinds of tris(acetylacetonato)metal(III), [M(III)(acac)(3)] (acac = acetylacetonato, M = Ru, Cr, Co, and Rh). It was deduced that the experimental spectra were well reproduced by the calculation with harmonic approximation in case of [Co(III)(acac)(3)] (d(6); S = 0), [Rh(III)(acac)(3)] (d(6); S = 0), and [Ru(III)(acac)(3)] (d(5); S = 1/2). In case of [Cr(III)(acac)(3)] (d(3); S = 3/2), anharmonic effects should be taken into account to predict the accurate vibrational frequencies of closely located modes. Time-dependent density functional theory calculations were performed to estimate the contribution of excited states in the VCD spectra. As a consequence, the presence of the low-lying excited states was predicted for [Ru(III)(acac)(3)] alone, which agreed with the experimental observation.     

Determination of the absolute configuration of three as-hydrindacene compounds by vibrational circular dichroism

[Structure: see text]. The absolute configurations of three compounds with a rigid 1,8-disubstituted as-hydrindacene skeleton have been determined using vibrational circular dichroism spectroscopy and quantum chemical calculations. Experimental spectra were compared to B3LYP/6-31G and B3LYP/cc-pVTZ level predicted spectra. Based on the agreement between the predicted and experimental spectra, the stereochemistry could be assigned with high confidence. The results were found to be in agreement with ECD determinations and/or predictions based on the applied asymmetric methods in the synthetic route.     

Signatures of counter-ion association and hydrogen bonding in vibrational circular dichroism spectra

We study the effect of counter-ion complexation on the example of Cl(-) ions interacting with the [Co(en)(3)](3+) complex. The H-bonding of the N-H groups of the ethylenediamine (en) ligands with the Cl(-) ions may lead to giant enhancement of the VCD intensity for the N-H stretches, but may also lead to VCD sign changes in the finger print region of N-H wagging, twisting and scissoring motions. Such sign changes should not be mistaken for signatures of the presence of the other enantiomer. We elucidate the mechanism for the sign changes and give a recommendation on how to deal with this problem. We also show that the experimental spectrum is only in good accord with the calculations if complexation of 5 Cl(-) ions (two axial, three equatorial) is assumed, but not with two (axial) or three (equatorial) Cl(-) ions, thus showing the potential of VCD to be used as an experimental probe for complexation.     

Vibrational-electronic interaction in the infrared circular dichroism spectra of transition-metal complexes

The circular dichroism spectra of the quasi-tetrahedral complexes of transition-metal ions with (?)-spartein, [M(l-sp)Cl₂], over the C-H stretching vibration range, show an optical activity which is weak in the Zn(II) case, but enhanced in the Co(II) and Ni(II) analogues through the coupling of the sharp vibrational transition with underlying broad d-d electronic excitation.     

Bile pigment complexes with cyclodextrins: electronic and vibrational circular dichroism study

Chiral recognition of bilirubin IX-α, biliverdin IX-α, and bilirubin ditaurate dianions by cyclodextrins was studied using a combination of vibrational and electronic circular dichroism. Biliverdin forms inclusion complexes with β-cyclodextrin and β-methylcyclodextrin. Bilirubin bonds to both cyclodextrins by means of hydrogen bonds and only shallow inclusions that are restricted by the presence of COO⁻ in the pigment structure. Bilirubin ditaurate complexes are realized by a weak inclusion of the whole molecule, or some part of it, into the cyclodextrin cavity and stabilization of the conformation by hydrogen bonds. Bilirubin and bilirubin ditaurate can be recognized by cyclodextrin and methylcyclodextrin in the form of opposite conformers. Spectroscopic characteristics of the different conformations of the bile pigments were obtained for the first time by vibrational circular dichroism techniques.     

Magnetic vibrational circular dichroism of the haloforms

The magnetic vibrational circular dichroism of the three haloforms, CHCl₃ CHBr₃ and CHI₃, is presented. In the a¹ symmetry C-H stretch B₀/D₀ increases from <10^t̄6 to ≈ 3 × 10⁻⁵/cm⁻¹ from Cl to I. These values are correlated to ΔE for electronic excitation and to the methyl halide results.     

On the equivalence of conformational and enantiomeric changes of atomic configuration for vibrational circular dichroism signs

We study systematically the vibrational circular dichroism (VCD) spectra of the conformers of a simple chiral molecule, with one chiral carbon and an "achiral" alkyl substituent of varying length. The vibrational modes can be divided into a group involving the chiral center and its direct neighbors and the modes of the achiral substituent. Conformational changes that consist of rotations around the bond from the next-nearest neighbor to the following carbon, and bond rotations further in the chain, do not affect the modes around the chiral center. However, conformational changes within the chiral fragment have dramatic effects, often reversing the sign of the rotational strength. The equivalence of the effect of enantiomeric change of the atomic configuration and conformational change on the VCD sign (rotational strength) is studied. It is explained as an effect of atomic characteristics, such as the nuclear amplitudes in some vibrational modes as well as the atomic polar and axial tensors, being to a high degree determined by the local topology of the atomic configuration. They reflect the local physics of the electron motions that generate the chemical bonds rather than the overall shape of the molecule.     

Elucidation of the absolute configuration of rhizopine by chiral supercritical fluid chromatography and vibrational circular dichroism

The absolute configuration of rhizopine, an opine‐like natural product present in nitrogen‐fixing nodules of alfalfa infected by rhizobia, is elucidated using a combination of state‐of‐the‐art analytical and semi‐preparative supercritical fluid chromatography and vibrational circular dichroism spectroscopy. A synthetic peracetylated racemate was fractionated into its enantiomers and subjected to absolute configuration analysis revealing that natural rhizopine exists as a single enantiomer. The stereochemistry of non‐derivatized natural rhizopine corresponds to (1R,2S,3R,4R,5S,6R)‐4‐amino‐6‐methoxycyclohexane‐1,2,3,5‐tetraol.     

Conformational flexibility of Corey lactone derivatives indicated by absorption and vibrational circular dichroism spectra

Infrared absorption and vibrational circular dichroism (VCD) spectra of four Corey lactone derivatives (diol, benzoate, p-phenylbenzoate, and bisbenzoate) were measured and analyzed on the basis of ab initio computations. The analysis interpreted most of the spectral features as well as the differences among individual compounds. Despite the common rigid lactone residue, conformational behaviors and spectral features of the derivatives were found to be different, because of hydrogen bonding and solvent effects. Recognition of common molecular parts in the spectra of different molecules increases the potential of using VCD for monitoring the purity of intermediates in chiral syntheses. For the derivatives, a conserved spectral component corresponding to the lactone skeleton could be identified on the basis of theoretical analysis but was relatively weak in intensity.     

Performance of conventional and range-separated hybrid density functionals in calculations of electronic circular dichroism spectra of transition metal complexes

A number of density functionals, including 'pure' (nonhybrid) functionals, global hybrids, and range-separated hybrids, were used to calculate the electronic circular dichroism (CD) spectra of 10 tris-bidentate transition metal complexes. The results are compared to one another and to experimental CD spectra, in an effort to illustrate the shortcomings of particular approximations in time-dependent density functional theory (TDDFT). The use of an origin invariant formalism to calculate magnetic transition dipole moments with the help of gauge-including atomic orbitals (GIAOs) is also investigated. With valence basis sets of moderate flexibility, good agreement between GIAO results and rotatory strengths calculated from the dipole-velocity representation is obtained for selected test cases. Empirically broadened vertical CD spectra calculated with the global hybrid functionals B3LYP and PBE0 are found to agree overall the best with experimental CD spectra.     

Synthesis and cytotoxic activity of new hexaazadibenzotetracenes derived from trans-1,2-diaminocyclohexane

A one-pot synthesis of N,N'-disubstituted (3bR*,7aR*,10bR*,14aR*)-octadecahydro-1H ,8H-2,3a,7b,9,10a,14b-hexaazadibenzo[fg, op]tetracenes via the catalytic heterocyclization of trans-1,6,7,12-tetraaza-perhydrotetracene with formaldehyde or CH₂(NMe₂)₂ and anilines has been accomplished. Preliminary screening of thus obtained perhydro hexaazadibenzotetracenes for cytotoxic activity has been performed.