Correction to: Exploration of selected electronic characteristics of half-sandwich organoruthenium(II) ß-diketonate complexes.

We would like to apologize for a wrong conclusion on the fourth page where the correlation of the Ru-P bond length and possible anticancer activity is discussed.

Exploration of selected electronic characteristics of half-sandwich organoruthenium(II) ß-diketonate complexes.

Based on experimental work, 12 half-sandwich organoruthenium(II) complexes with p-cymene and various substituted ß-diketonates (acac) modified by several functional groups were explored. These complexes were optimized at the B3PW91/6-31 + G(d)/PCM/UFF computational level with the Ru atom described by Stuttgart pseudopotentials. The electron density analysis was performed using the B3LYP/ 6-311++G(2df,2pd)/DPCM/scaled-UAKS model. Electrostatic and averaged local ionization potential were explored and extremes on 0.001 e/a.u.3 isodensity surfaces discussed. Natural population analysis partial charges and electron densities in bond critical point of the key Ru(II) coordination bonds were determined. There was a clear correlation between the results obtained and experimentally known anticancer descriptors. Graphical abstract Top Average local ionization potential (ALIP) of half-sandwich organoruthenium(II) ß-diketonate complex, bottom IC 50 of b-series for ovarian cancer and Ru-P distances (in Å).

Chemical shifts in nucleic acids studied by density functional theory calculations and comparison with experiment.

NMR chemical shifts are highly sensitive probes of local molecular conformation and environment and form an important source of structural information. In this study, the relationship between the NMR chemical shifts of nucleic acids and the glycosidic torsion angle, χ, has been investigated for the two commonly occurring sugar conformations. We have calculated by means of DFT the chemical shifts of all atoms in the eight DNA and RNA mono-nucleosides as a function of these two variables. From the DFT calculations, structures and potential energy surfaces were determined by using constrained geometry optimizations at the BP86/TZ2P level of theory. The NMR parameters were subsequently calculated by single-point calculations at the SAOP/TZ2P level of theory. Comparison of the (1)H and (13)C NMR shifts calculated for the mono-nucleosides with the shifts determined by NMR spectroscopy for nucleic acids demonstrates that the theoretical shifts are valuable for the characterization of nucleic acid conformation. For example, a clear distinction can be made between χ angles in the anti and syn domains. Furthermore, a quantitative determination of the χ angle in the syn domain is possible, in particular when (13)C and (1)H chemical shift data are combined. The approximate linear dependence of the C1' shift on the χ angle in the anti domain provides a good estimate of the angle in this region. It is also possible to derive the sugar conformation from the chemical shift information. The DFT calculations reported herein were performed on mono-nucleosides, but examples are also provided to estimate intramolecularly induced shifts as a result of hydrogen bonding, polarization effects, or ring-current effects.

Guanine bases in DNA G-quadruplex adopt nonplanar geometries owing to solvation and base pairing.

The effect of base pairing and solvation on pyramidalization of the glycosidic nitrogen found in the residues of parallel G-quadruplex with NDB ID UDF062 is analyzed and explained with theoretical calculations. The extent of the pyramidalization depends on the local geometry of the 2'-deoxyguanosine residues, namely on their glycosidic torsion and sugar pucker, which are predetermined by the 3D-architecture of G-quadruplex. Pyramidal inversion of the glycosidic nitrogen found in 2'-deoxyguanosines of G-quadruplex is induced owing to site-specifically coordinated solvent. Different adiabatic structural constraints used for fixing the base-to-sugar orientation of 2'-deoxyguanosine in geometry optimizations result in different extents of pyramidalization and induce pyramidal inversion of the glycosidic nitrogen. These model geometry constraints helped us analyze the effect of real constraints represented by explicit molecular environment of selected residues of the G-quadruplex. The maximal extent of the glycosidic nitrogen pyramidalization found in the high-resolution crystal structure corresponds to the calculation to deformation energy of only 1 kcal mol(-1). The out-of-plane deformations of nucleobases thus provide a way for compensating the site-specific external environmental stress on the G-quadruplex.

Correlating the 31P NMR chemical shielding tensor and the 2J(P,C) spin-spin coupling constants with torsion angles ζ and α in the backbone of nucleic acids.

Determination of nucleic acid (NA) structure with NMR spectroscopy is limited by the lack of restraints on conformation of NA phosphate. In this work, the (31)P chemical shielding tensor, the Γ(P,C5'H5'1) and Γ(P,C5'H5'2) cross-correlated relaxation rates, and the (2)J(P,C3'), (2)J(P,C5'), and (3)J(P,C4') coupling constants were calculated in dependence on NA backbone torsion angles ζ and α. While the orientation of the (31)P chemical shielding tensor was almost independent of the NA phosphate conformation, the principal tensor components varied by up to ~40 ppm. This variation and the dependence of the phosphate geometry on torsion angles ζ and α had only a minor influence on the calculated Γ(P,C5'H5'1) and Γ(P,C5'H5'2) cross-correlated relaxation rates, and therefore, the so-called rigid tensor approximation was here validated. For the first time, the (2)J(P,C) spin-spin coupling constants were correlated with the conformation of NA phosphate. Although each of the two J-couplings was significantly modulated by both torsions ζ and α, the (2)J(P,C3') coupling could be structurally assigned to torsion ζ and the (2)J(P,C5') coupling to torsion α. We propose qualitative rules for their structural interpretation as loose restraints on torsion angles ζ and α. The (3)J(P,C4') coupling assigned to torsion angle ß was found dependent also on torsions ζ and α, implying that the uncertainty in determination of ß with standard Karplus curves could be as large as ~25°. The calculations provided a unified picture of NMR parameters applicable for the determination of NA phosphate conformation.

Evaluating the effects of the nonplanarity of nucleic acid bases on NMR, IR, and vibrational circular dichroism spectra: a density functional theory computational study.

The pyramidalizations of N9/1 glycosidic nitrogens in DNA and RNA nucleosides, recently discovered and analyzed in their ultrahigh-resolution X-ray crystal structures ( Sychrovský ; et al. Nucleic Acid Res. 2009 , 37 , 7321. ), were found to have significant effects on the structural interpretation of the (3)J(C4/2-H1') and (3)J(C8/6-H1') NMR scalar couplings in purine/pyrimidine nucleosides. The calculated effects on IR and vibrational circular dichroism (VCD) spectra were only minor. The calculated structural deformations in nucleosides, depending on sugar-to-base orientation, gave rise to corrections in the phase shift of the Karplus equations for the (3)J(C8/6-H1') and (3)J(C4/2-H1') couplings ranging from -26° to +25° and from -5.7° to +2.0°, respectively. The sign alternation of this correction in syn and anti nucleosides arises from the stereoinversion of the N9/1 glycosidic nitrogen occurring upon reorientation of the glycosidic torsion. The effect was calculated consistently in the dG, dA, dC, dT, rA, and rG nucleosides. Utilization of the calculated phase-shift corrections in the design of Karplus equations for the (3)J couplings was suggested, and the effects on structural interpretation of the experimental couplings were evaluated.

Charge transport in DNA oligonucleotides with various base-pairing patterns.

We combined various experimental (scanning tunneling microscopy and Raman spectroscopy) and theoretical (density functional theory and molecular dynamics) approaches to study the relationships between the base-pairing patterns and the charge transfer properties in DNA 32-mer duplexes that may be relevant for identification and repair of defects in base pairing of the genetic DNA and for DNA use in nanotechnologies. Studied were two fully Watson-Crick (W-C)-paired duplexes, one mismatched (containing three non-W-C pairs), and three with base pairs chemically removed. The results show that the charge transport varies strongly between these duplexes. The conductivity of the mismatched duplex is considerably lower than that of the W-C-paired one despite the fact that their structural integrities and thermal stabilities are comparable. Structurally and thermally much less stable abasic duplexes have still lower conductivity but not markedly different from the mismatched duplex. All duplexes are likely to conduct by the hole mechanism, and water orbitals increase the charge transport probability.

Revisiting the planarity of nucleic acid bases: Pyramidilization at glycosidic nitrogen in purine bases is modulated by orientation of glycosidic torsion.

We describe a novel, fundamental property of nucleobase structure, namely, pyramidilization at the N1/9 sites of purine and pyrimidine bases. Through a combined analyses of ultra-high-resolution X-ray structures of both oligonucleotides extracted from the Nucleic Acid Database and isolated nucleotides and nucleosides from the Cambridge Structural Database, together with a series of quantum chemical calculations, molecular dynamics (MD) simulations, and published solution nuclear magnetic resonance (NMR) data, we show that pyramidilization at the glycosidic nitrogen is an intrinsic property. This property is common to isolated nucleosides and nucleotides as well as oligonucleotides-it is also common to both RNA and DNA. Our analysis suggests that pyramidilization at N1/9 sites depends in a systematic way on the local structure of the nucleoside. Of note, the pyramidilization undergoes stereo-inversion upon reorientation of the glycosidic bond. The extent of the pyramidilization is further modulated by the conformation of the sugar ring. The observed pyramidilization is more pronounced for purine bases, while for pyrimidines it is negligible. We discuss how the assumption of nucleic acid base planarity can lead to systematic errors in determining the conformation of nucleotides from experimental data and from unconstrained MD simulations.

Structural interpretation of J coupling constants in guanosine and deoxyguanosine: modeling the effects of sugar pucker, backbone conformation, and base pairing.

The (3)J(C8-H1'), (3)J(C4-H1'), (1)J(C8-H8), (1)J(C1'-H1'), (1)J(C2'-H2'), and (1)J(C2'-H2'2) indirect scalar coupling constants were calculated with the density functional theory in the deoxyguanosine and riboguanosine molecules. The following geometry descriptors were considered in analysis of the structural dependence of the six J couplings: the glycosidic torsion angle chi and conformation of the hydroxymethyl group at the C4' carbon of sugar mimicking the backbone residue and the sugar pucker (C2'-, C3'-endo). The (3)J(C8-H1') and (3)J(C4-H1') couplings, which are typically assigned to the chi torsion, also depended on the sugar pucker, although the calculated dependence of the latter coupling on sugar pucker was nearly negligible. New parametrization of the Karplus equations, taking into account the stereoinversion effect at the glycosidic nitrogen atom and solvent effects, was calculated for the (3)J(C8-H1') and (3)J(C4-H1') coupling assigned to the chi torsion. The calculated phase shift of chi torsion angle in these new Karplus equations was larger by approximately 10 degrees compared to its commonly accepted value of 60 degrees (Wijmenga, S. S.; van Buuren, B. N. M. Prog. NMR Spectrosc. 1998, 32, 287.). The calculated (1)J(C2'-H2') and (1)J(C2'-H2'2) coupling dominantly depended on the sugar type (deoxyribose or ribose) and its pucker, while the (1)J(C1'-H1') and (1)J(C8-H8) coupling dominantly depended on the glycosidic torsion angle, although quantitatively, all four (1)J couplings depended on both geometry parameters. The dependences of j-couplings on the torsion angle chi calculated in isolated nucleosides were compared with those taking into account the effect of base pairing occurring in the WC/SE RNA base pair family, which appeared to be minor. The calculated (3)J couplings agreed well with available experimental data similarly as the (1)J couplings, although lack of experimental data diminished more reliable validation of the later couplings.

Structure and dynamics of the ApA, ApC, CpA, and CpC RNA dinucleoside monophosphates resolved with NMR scalar spin-spin couplings.

The measured NMR scalar coupling constants (J-couplings) in the XpY, (X,Y = adenine (A) or cytosine (C)) RNA dinucleoside monophosphates (DMPs) were assigned to the backbone (alpha, beta, gamma, delta, epsilon, zeta) and glycosidic (chi) torsion angles in order to resolve the global structure of the DMP molecules. The experimental J-couplings were correlated with the theoretical J-couplings obtained as the dynamical averages of the Karplus equations relevant to the torsion angles. The dynamical information was captured using the molecular dynamics (MD) calculation method. The individual conformational flexibility of the four DMP molecules was thus consistently probed with the NMR J-couplings. The calculated structure and flexibility of the DMP molecules depend on the sequence considered with respect to the 5' and 3' end of the DMP molecules (5'-XpY-3'). The dynamical characteristics of the two nucleosides are not equivalent even for the ApA and CpC homologues. An enhancement of the sampling in the MD calculations was achieved using five different starting structural motives classified previously for the RNA backbone in the solid phase (Richardson et al. RNA 2008, 14, 465-481). The initial structures were selected on the basis of a database search for RNA oligonucleotides. Frequent interconversions between the conformers during the MD calculations were actually observed. The structural interpretation of the NMR spectroscopic data based on the MD simulations combined with the Karplus equations indicates that the dominant conformation of the DMP molecules in solution corresponds to the A-RNA form. For 52% of the total simulation time (1000 ns), the zeta(g-)-alpha(g-)-gamma(g+) backbone topology corresponding to the canonical A-RNA form was observed, with roughly equally populated C2'- and C3'-endo sugar puckers interconverting on the nanosecond time scale. However, other noncanonical patterns were also found and thus indicate their relatively high potential to be populated in the dynamical regime. For approximately 72% of the time portion when the A-RNA of the zeta-alpha-gamma combination occurred, the nucleobases were classified as being mutually stacked. The geometries of the nucleobases classified in this work as stacked were significantly more populated for the DMP molecules with adenosine at the 3' end (ApA and CpA DMPs) than the ApC or CpC RNA molecules with C at the 3' end.

Effect of local sugar and base geometry on 13C and 15N magnetic shielding anisotropy in DNA nucleosides.

Density functional theory was employed to study the dependence of 13C and 15N magnetic shielding tensors on the glycosidic torsion angle (chi) and conformation of the sugar ring in 2'-deoxyadenosine, 2'-deoxyguanosine, 2'-deoxycytidine, and 2'-deoxythymidine. In general, the magnetic shielding of the glycosidic nitrogens and the sugar carbons was found to depend on both the conformation of the sugar ring and chi. Our calculations indicate that the magnetic shielding anisotropy of the C6 atom in pyrimidine and the C8 atom in purine bases depends strongly on chi. The remaining base carbons were found to be insensitive to both sugar pucker and chi re-orientation. These results call into question the underlying assumptions of currently established methods for interpreting residual chemical shift anisotropies and 13C and 15N auto- and cross-correlated relaxation rates and highlight possible limitations of DNA applications of these methods.

Dependence of the L-alanyl-L-alanine conformation on molecular charge determined from ab initio computations and NMR spectra.

The l-alanyl-l-alanine (AA) molecule behaves differently in acidic, neutral, and basic environments. Because of its molecular flexibility and strong interaction with the aqueous environment, its behavior has to be deduced from the NMR spectra indirectly, using statistical methods and comparison with ab initio predictions of geometric and spectral parameters. In this study, chemical shifts and indirect spin-spin coupling constants of the AA cation, anion, and zwitterion were measured and compared to values obtained by density functional computations for various conformers of the dipeptide. The accuracy and sensitivity of the quantum methods to the molecular charge was also tested on the (mono)-alanine molecule. Probable AA conformers could be identified at two-dimensional potential energy surfaces and verified by the comparison of the computed parameters with measured NMR data. The results indicate that, whereas the main-chain peptide conformations of the cationic (AA+) and zwitterionic (AAZW) forms are similar, the anion (AA-) adopts also another, approximately equally populated conformer in the aqueous solution. Additionally, the NH2 group can rotate in the two main chain conformations of the anionic form AA-. According to a vibrational quantum analysis of the two-dimensional energy surfaces, higher-energy conformers might exist for all three charged AA forms but cannot be detected directly by NMR spectroscopy because of their small populations and short lifetimes. In accord with previous studies, the NMR parameters, particularly the indirect nuclear spin-spin coupling constants, often provided an excellent probe of a local conformation. Generalization to peptides and proteins, however, has to take into account the environment, molecular charge, and flexibility of the peptide chain.

Theoretical study of the scalar coupling constants across the noncovalent contacts in RNA base pairs: the cis- and trans-watson-crick/sugar edge base pair family.

The structure and function of RNA molecules are substantially affected by non-Watson-Crick base pairs actively utilizing the 2'-hydroxyl group of ribose. Here we correlate scalar coupling constants across the noncovalent contacts calculated for the cis- and trans-WC/SE (Watson-Crick/sugar edge) RNA base pairs with the geometry of base to base and sugar to base hydrogen bond(s). 23 RNA base pairs from the 32 investigated were found in RNA crystal structures, and the calculated scalar couplings are therefore experimentally relevant with regard to the binding patterns occurring in this class of RNA base pairs. The intermolecular scalar couplings 1hJ(N,H), 2hJ(N,N), 2hJ(C,H), and 3hJ(C,N) were calculated for the N-H...N and N-H...O=C base to base contacts and various noncovalent links between the sugar hydroxyl and RNA base. Also, the intramolecular 1J(N,H) and 2J(C,H) couplings were calculated for the amino or imino group of RNA base and the ribose 2'-hydroxyl group involved in the noncovalent interactions. The calculated scalar couplings have implications for validation of local geometry, show specificity for the amino and imino groups of RNA base involved in the linkage, and can be used for discrimination between the cis- and trans-WC/SE base pairs. The RNA base pairs within an isosteric subclass of the WC/SE binding patterns can be further sorted according to the scalar couplings calculated across different local noncovalent contacts. The effect of explicit water inserted in the RNA base pairs on the magnitude of the scalar couplings was calculated, and the data for discrimination between the water-inserted and direct RNA base pairs are presented. The calculated NMR data are significant for structural interpretation of the scalar couplings in the noncanonical RNA base pairs.

Computational study on spectral properties of the selected pigments from various photosystems: structure-transition energy relationship.

In this study, the most important kinds of pigments (chlorophylls, bacteriochlorophylls, phycobilins, and carotenoids) from various photosystems were explored. For the most stable conformations, electronic transitions were determined at the TDDFT/6-31+G(d) level with the B3PW91 functional and compared to measured spectra. The group of carotenoids was also investigated at the TDA/TDDFT level with the BLYP functional. The energies of Qy transitions are systematically blue-shifted by about 50-100 nm in the case of (bacterio)chlorophyll and pheophytin molecules. Nevertheless, the correct relative order of the Q lines among various chlorophyll types was obtained through comparison with experimental results. Much better agreement was obtained for the Soret band, for which the differences between calculated and measured transitions were at most 35 nm. In the case of phycobilins, the first transition line was estimated to be at lower frequencies (around 500 nm) with a very similar blue shift of about 100 nm from experimental values. The influence of anchoring cysteine side chain(s) was found to be marginal. A dominant effect of the linear polyene chain on the determined spectral lines was found in the case of carotenoids. Nevertheless, the impact of beta-cycles and epoxy and keto groups is clearly visible as well. The high intensity of the first allowed transition matches different characters of the HOMO and LUMO. In the case of fucoxanthin, the TDA method also predicts the Bu- state to lie below the 1Bu+ state. Because the shift of electron transitions is approximately proportional to the size of the pi-conjugated system, the shift of the calculated transitions compared to experimental values is practically constant for the same excitations of (bacterio)chlorophyll and phycobilin molecules. However, this is not true for carotenoids, for which both the transition energy and the shift of the transition vary with the number of conjugated double bonds.

Calculation of structural behavior of indirect NMR spin-spin couplings in the backbone of nucleic acids.

Calculated indirect NMR spin-spin coupling constants (J-couplings) between (31)P, (13)C, and (1)H nuclei were related to the backbone torsion angles of nucleic acids (NAs), and it was shown that J-couplings can facilitate accurate and reliable structural interpretation of NMR measurements and help to discriminate between their distinct conformational classes. A proposed stepwise procedure suggests assignment of the J-couplings to torsion angles from the sugar part to the phosphodiester link. Some J-couplings show multidimensional dependence on torsion angles, the most prominent of which is the effect of the sugar pucker. J-couplings were calculated in 16 distinct nucleic acid conformations, two principal double-helical DNAs, B- and A-, the main RNA form, A-RNA, as well as in 13 other RNA conformations. High-level quantum mechanics calculations used a baseless dinucleoside phosphate as a molecular model, and the effect of solvent was included. The predicted J-couplings correlate reliably with available experimental data from the literature.