The present study (see ref 1) delineates the scope and limitations of porphyrin chromophores for structural studies by the exciton coupled circular dichroic (CD) method. A distance dependency of the porphyrin coupling was investigated in the range between 10 and 50 Å. Over short interchromophoric distances, significant changes in the conformational distribution introduced by the bulky porphyrin chromophores were observed. Over longer distances, the porphyrins showed ca. 10-fold sensitivity increase over commonly used chromophores, and an effective direction for the interacting porphyrin transition moments was assigned by comparison. Porphyrins at the termini of dimeric steroids and brevetoxin B exhibited exciton coupling over interchromophoric distances up to 50 Å. These results represent the porphyrins as promising reporter chromophores for extending the exciton coupled CD method to structural studies of biopolymers.

Circular dichroism (CD) spectroscopy is widely used to characterize the structures of DNA G-quadruplexes. CD bands at 200-300 nm have been empirically related to G-quadruplexes having parallel or antiparallel sugar-phosphate backbones. We propose that a more fundamental interpretation of the origin of the CD bands is in the stacking interactions of neighboring G-quartets, which can have the same or opposing polarities of hydrogen bond acceptors and donors. From an empirical summation of CD spectra of the d(G)5 G-quadruplex and of the thrombin binding aptamer that have neighboring G-quartets with the same and opposite polarities, respectively, the spectra of aptamers selected by the Ff gene 5 protein (g5p) appear to arise from a combination of the two types of polarities of neighboring G-quartets. The aptamer CD spectra resemble the spectrum of d(G3T4G3), in which two adjacent quartets have the same and two have opposite polarities. Quantum-chemical spectral calculations were performed using a matrix method, based on guanine chromophores oriented as in d(G3T4G3). The calculations show that the two types of G-quartet stacks have CD spectra with features resembling experimental spectra of the corresponding types of G-quadruplexes.

Chiral bis-porphyrins are currently the subject of intense interest as chiral receptors and as probes in the determination of structure and stereochemistry. To provide an improved framework for interpreting the circular dichroism (CD) spectra of bis-porphyrins, we have calculated the CD spectra of chiral bis-porphyrins from three classes: I, where porphyrins can adopt a relatively wide range of orientations relative to each other; II, porphyrins have a fixed relative orientation; III, porphyrins undergo pi-stacking. The calculations primarily utilized the classical polarizability theory of DeVoe, but were supplemented by the quantum mechanical matrix method. Class I was represented by three isomers of the diester of 5alpha-cholestane-3,17-diol with 5-(4'-carboxyphenyl)-10,15,20-triphenylporphin (2-alphabeta, 2-betaalpha, 2-betabeta). Careful analysis of the torsional degrees of freedom led to two to four minimum-energy conformers for each isomer, in each of which the phenyl-porphyrin bonds had torsional angles near 90 degrees. Libration about these bonds is relatively unrestricted over a range of +/-45 degrees. CD spectra in the Soret region were calculated as Boltzmann-weighted averages over the low-energy conformers for each isomer. Three models were used: the effective transition moment model, in which only one of the degenerate Soret components is considered, along the 5-15 direction; the circular oscillator model, in which both Soret components are given equal weight; and the hybrid model, in which the 10-20 oscillator is given half the weight of the 5-15 oscillator, to mimic the effect of extensive librational averaging about the 5-15 direction. All three models predict Soret exciton couplets with signs in agreement with experiment. Quantitatively, the best results are given by the hybrid and circular oscillator models. These results validate the widely used effective transition moment model for qualitative assignments of bis-porphyrin chirality and thus permit application of the exciton chirality model. However, for quantitative studies, the circular oscillator or hybrid models should be used. The simplified effective transition moment and hybrid models are justified by the librational averaging in the class I bis-porphyrins and should only be used with such systems. Two class II bis-porphyrins were also studied by DeVoe method calculations in the circular oscillator model, which yielded good agreement with experiment. Class III bis-porphyrins were represented by 2-alphaalpha, for which the calculations gave qualitative agreement. However, limitations in the conformational analysis with the close contacts and dynamic effects in these pi-stacked systems preclude quantitative results.

The LCAO version of the perimeter model with overlap through second order is used to treat the ππ* electronic absorption and magnetic circular dichroism (MCD) of low-symmetry molecules with a closed-shell ground state and no degenerate states (no threefold or higher order axis) derived from biradical (antiaromatic) parent 4N-electron [n]annulene perimeters by structural perturbations. If a symmetry plane perpendicular to the molecular plane is present, simple explicit algebraic solutions are obtained. Rules are derived for predicting the intensities, polarizations, and MCD signs of low-energy transitions in this class of molecules from the knowledge of relative magnitudes of MO energy differences, which can be frequently deduced by mere inspection of molecular formulas. On the basis of the results, a generalized nomenclature is proposed for low-energy electronic excited states of all even-electron cyclic π systems with a single perimeter.

Investigation of the fungal strain Monodictys putredinis isolated from the inner tissue of a marine green alga led to the isolation of four new monomeric xanthones and a benzophenone. All structures were elucidated by extensive spectroscopic measurements. The relative configuration of compound 1 was determined by X-ray crystal structure analysis, while for 2 and 3 configurations were confirmed by NOE experiments. Absolute configurations for compounds 1-3 were deduced by comparing experimental circular dichroism spectroscopic data with those calculated employing quantum-chemical time-dependent density functional theory (TDDFT). The compounds were examined for their cancer chemopreventive potential. Xanthone 2 was shown to inhibit cytochrome P450 1A activity with an IC50 value of 3.0 microM. Compounds 2 and 3 displayed moderate activity as inducers of NAD(P)H:quinone reductase (QR) in cultured mouse Hepa 1c1c7 cells, with CD values (concentration required to double the specific activity of QR) of 12.0 and 12.8 microM, respectively. Compound 3 showed weak inhibition of aromatase activity.

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Ab initio calculations of the (methylsulfonyl)methyl anion (1), the ((trifluoromethyl)sulfonyl)methyl anion (1T), the (fluorosulfonyl)methyl anion (1F), and the (methylsulfonyl)isopropyl anion (1D) at the HF/6-31+G*//HF/6-31+G* level revealed a significant effect of fluorine substitution upon the structure and energy of α-sulfonyl carbanions. The Cα−S bond in 1T and 1F is shorter and the pyramidalization of the anionic carbon atom is less than in 1. In the anions 1T and 1F the Cα−S bond is shortened and the S−CF3(F) and the S−O bonds are lengthened as compared to the sulfones 3T and 3F. For all anions the staggered conformation (1, 1T, 1F, 1D) is energetically more stable than the eclipsed conformation (2, 2T, 2F, 2D). At the MP2/6-31+G*//HF/6-31+G* level the energy difference between the staggered and the eclipsed conformation is much larger for the fluorinated anions 1T and 1F than for 1 and 1D. The rotational barriers about the Cα−S bond of the fluorinated species 1T and 1F are in accordance with related experimental results significantly higher than the barriers of the non-fluorinated species 1 and 1D. A Fourier series analysis of the rotational potential curves shows the dominance of a positive V 2 term (conjugative overlap effects) which is much higher for 1T and 1F than for 1 and 1D. Negative hyperconjugation (nC−σ*SR) is an important mechanism which determines the conformation of the anions and particularly of the fluorinated anions. In the dimethyl anion 1D, which has a strongly pyramidalized anionic carbon atom, the V 3 term (steric and torsional effects) also contributes significantly to the rotational barrier. The configurational stability of chiral α-sulfonyl carbanions thus depends on the height of the Cα−S rotational barrier which is determined by nC−σ*SR interaction and the steric contribution of the substituents. The calculations suggest that S-(trifluoromethyl) substitution of other S-stabilized carbanions should lead also to derivatives of a higher configurational stability.

CD spectra of bovine pancreatic ribonuclease A (RNase A) and its subtilisin-modified from (RNase S) have been calculated, based upon high-resolution structures from x-ray diffraction. All known transitions in the peptide and side-chain groups, especially the aromatic and disulfide groups, have been included. Calculations have been performed with both the matrix method and with first-order perturbation theory. A newly developed method for treating the electrostatic interactions among transition charge densities and between static charge distributions and transition charge densities is used. The effects of local electrostatic fields upon the group transition energies are included for all transitions. Rotational strengths generated by the matrix method were combined with Gaussian band shapes to generate theoretical CD spectra. The calculated spectra reproduce the signs and approximate magnitudes of the near-uv CD bands of both RNase A and S. Agreement is most satisfactory for the negative 275 nm band, dominated by tyrosine contributions. In agreement with two previous studies by other workers, coupling between Tyr 73 and Tyr 115 is the single most important factor in this band. The positive band observed near 240 nm is dominated by disulfide contributions, according to our results. The far-uv CD spectrum is poorly reproduced by the calculations. The observed 208 nm band, characteristic of alpha-helices, is absent from the calculated spectrum, probably because the helices in RNase are short. A strong positive couplet centered near 190 nm is predicted but not observed. Possible reasons for these incorrect predictions of the current theoretical model in the far-uv are discussed.