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The four-stranded G-quadruplex motif is a conformation frequently adopted by guanine-rich nucleic acids that plays an important role in biology, medicine, and nanotechnology. Although vibrational spectroscopy has been widely used to investigate nucleic acid structure, association of particular spectral features with the quadruplex structure has to date been ambiguous. In this work, experimental IR absorption and vibrational circular dichroism (VCD) spectra of the model quadruplex systems d(G)(8) and deoxyguanosine-5'-monophosphate (5'-dGMP) were analyzed using molecular dynamics (MD) and quantum-chemical modeling. The experimental spectra were unambiguously assigned to the quadruplex DNA arrangement, and several IR and VCD bands related to this structural motif were determined. Involvement of MD in the modeling was essential for realistic simulation of the spectra. The VCD signal was found to be more sensitive to dynamical structural variations than the IR signal. The combination of the spectroscopic techniques with multiscale simulations provides extended information about nucleic acid conformations and their dynamics.

Raman and Raman optical activity spectra of L- and D-proline zwitterionic (PROZW) forms were recorded for H(2)O and D(2)O solutions in a wide frequency range and analyzed with respect to the motion of the proline ring and rotation of the carbonyl group. The solution spectra were additionally compared to Raman scattering of glass and crystalline powder proline. Solution and glass spectral band broadenings are similar and reveal information about the extent of internal molecular motion. Two distinct but equally populated flexible forms were found in the glass and the solution. The equal population is consistent with NMR data, temperature, and concentration dependencies. The molecular flexibility is reduced significantly in the crystal, however, where only one conformer is present. Consequently, the crystal bands are narrow and exhibit minor frequency shifts. The spectra were interpreted with the aid of density functional theory computations involving both continuum and explicit solvent. A two-dimensional potential energy surface pertaining to the five-member ring puckering coordinates was constructed and used for dynamical averaging of spectral properties. Comparison of the computed and experimental bandwidths suggests that the puckering is strongly correlated with the carbonyl rotation. An averaging over these two motions produces similar results. The interpretation of the Raman experiments with the aid of the simulation techniques also indicates that the environment modulates properties of the hydrophobic part of the molecule indirectly by interacting with the ionic group. Such behavior may be important for the reactivity and biological activity of proline-containing peptides and proteins.

Raman and Raman optical activity (ROA) spectra of poly-L-proline were recorded in a wide frequency range and analyzed with respect to the proline side chain conformation. The analysis was based on comparison to ab initio simulations of spectral band positions and intensities. The presence of two conformer states of the five-member ring was found, approximately equally populated in the polypeptide. Additionally, Raman and ROA spectral shapes indicated that the peptide adopts the polyproline II helical conformation, in both aqueous and TFE solutions. The helix, however, is perturbed by fluctuations, which affects the vibrational coupling among amino acid residues and broadens the ROA bands. Contributions of the side and main peptide chains to the polyproline ROA intensities have comparable magnitudes. Thus understanding of the origins of both signals is important for determination of the peptide structure by ROA.

With the aid of labeling with stable isotopes ((15)N and (13)C) a complete set of chemical shifts and indirect spin-spin coupling constants was obtained for the zwitterionic form of L-alanyl-L-alanine in aqueous solution. Different sensitivities of the NMR parameters to the molecular geometry were discussed on the basis of comparison with ab initio (DFT) calculated values. An adiabatic two-dimensional vibrational wave function was constructed and used for determination of the main chain torsion angle dispersions and conformational averaging of the NMR shifts and coupling constants. The quantum description of the conformational dynamics based on the density functional theory and a polarizable continuum solvent model agrees reasonably with classical molecular dynamics simulations using explicit solvent. The results consistently evidence the presence of a single form in the aqueous solution with equilibrium main chain torsion angle values (psi = 147 degrees, varphi = -153 degrees), close to that one found previously in an X-ray study. Under normal temperature the torsion angles can vary by about 10 degrees around their equilibrium values, which leads, however, to minor corrections of the NMR parameters only. The main chain heavy atom chemical shifts and spin-spin coupling constants involving the alpha-carbon and hydrogen atoms appear to be most useful for the peptide structural predictions.

A new, stepwise synthesis of calix[4]phyrins is described. It relies on the condensation of a ketone with pyrrole to form a dipyrromethane containing a quaternary carbon center that is subsequently condensed with an aromatic aldehyde. This methodology, in contrast to the previous rational approach described by this group (involving formation of a trisubstituted dipyrromethane via the condensation of an aldehyde with pyrrole, followed by condensation of this dipyrromethane with acetone), allows for a variety of bulky, ketone-derived substituents to be incorporated into the meso-like positions. The resulting systems, while all containing the same central macrocyclic core, display conformational properties that reflect the nature of these meso-like substituents; these conformational features were independently assessed by X-ray diffraction analysis, NMR spectroscopy, and quantum chemical calculations., (Copyright 2004 American Chemical Society)