Molecular dynamics investigation of the interaction between DNA and distamycin

The complex of the minor groove binding drug distamycin and the B-DNA oligomer d-(CGCAAATTTGCG) was investigated by molecular dynamics simulations. For this purpose, accurate atomic partial charges of distamycin were determined by extended quantum chemical calculations. The complex was simulated without water but with hydrated counterions. The oligomer without the drug was simulated in the same fashion and also with 1713 water molecules and sodium counterions. The simulations revealed that the binding of distamycin in the minor groove induces a stiffening of the DNA helix. The drug also prevents a transition from B-DNA to A-DNA that was found to occur rapidly (30 ps) in the segment without bound distamycin in a water-free environment but not in simulations including water. In other simulations, we investigated the relaxation processes after distamycin was moved from its preferred binding site, either radially or along the minor groove. Binding in the major groove was simulated as well and resulted in a bound configuration with the guanidinium end of distamycin close to two phosphate groups. We suggest that, in an aqueous environment, tight hydration shells covering the DNA backbone prevent such an arrangement and thus lead to distamycin's propensity for minor groove binding.     

A quantum chemical investigation of structures,vibrational spectra and electron affinities of the radicals of quinone model compounds

In the present study, the first quantum chemical calculations of structures and vibrational spectra of radicals of 1,4-naphthoquinone and 2-methoxy-1,4-benzoquinone that account for electron correlation are presented. In the case of 1,4-naphthoquinone a good agreement between calculated vibrational frequencies and ¹⁸O-shifts of the 1,4-naphthoquinone radical (protonated radical anion) with experimental data of a species detected after irradiation of vitamin K₁ in solution is found. Our calculations, thus, support the previous assignment. In the case of 2-methoxy-1,4-benzoquinone we have localized the stable conformations with respect to the orientation of the methoxy group and we have determine the harmonic force fields for these structures. Our calculation suggest that, while the frequencies of the two conformers are similar, the ¹⁸O-shift of the most intensive absorptions in the spectral region between 1400 and 1700 cm^–1 of the two conformers differ significantly and might serve as a tool to distinguish between the two conformers. The applied DFT method is shown to predict electron affinities which are systematically underestimated by 10%.     

Site-specific isotope labeling demonstrates a large mesomeric resonance effect of the methoxy groups on the carbonyl frequency in ubiquinones

The splitting of the carbonyl infrared bands of 2-methoxy-1,4-benzoquinone in solution can be related to a mesomeric resonance phenomenon leading to a conformation of the O-CH₃ bond coplanar to the quinone ring. The delocalization of the electron density induces a frequency downshift of the C₄=O carbonyl compared to 1,4-benzoquinone. This in turns decouples the two carbonyls leading to an upshift of the C₁=O vibration. Using selective ¹³C-labeling of Q₀ (2,3-dimethoxy-5-methyl-1,4-benzoquinone), we show that the effect of mesomeric resonance is an essential determinant of the carbonyl frequencies of ubiquinone in solution.