An ab initio and AIM investigation into the hydration of 2-thioxanthine

<p>Abstract</p> <p>Background</p> <p>Hydration is a universal phenomenon in nature. The interactions between biomolecules and water of hydration play a pivotal role in molecular biology. 2-Thioxanthine (2TX), a thio-modified nucleic acid base, is of significant interest as a DNA inhibitor yet its interactions with hydration water have not been investigated either computationally or experimentally. Here in, we reported an <it>ab initio </it>study of the hydration of 2TX, revealing water can form seven hydrated complexes.</p> <p>Results</p> <p>Hydrogen-bond (H-bond) interactions in 1:1 complexes of 2TX with water are studied at the MP2/6-311G(d, p) and B3LYP/6-311G(d, p) levels. Seven 2TX^...H₂O hydrogen bonded complexes have been theoretically identified and reported for the first time. The proton affinities (PAs) of the O, S, and N atoms and deprotonantion enthalpies (DPEs) of different N-H bonds in 2TX are calculated, factors surrounding why the seven complexes have different hydrogen bond energies are discussed. The theoretical infrared and NMR spectra of hydrated 2TX complexes are reported to probe the characteristics of the proposed H-bonds. An improper blue-shifting H-bond with a shortened C-H bond was found in one case. NBO and AIM analysis were carried out to explain the formation of improper blue-shifting H-bonds, and the H-bonding characteristics are discussed.</p> <p>Conclusion</p> <p>2TX can interact with water by five different H-bonding regimes, N-H^...O, O-H^...N, O-H^...O, O-H^...S and C-H^...O, all of which are medium strength hydrogen bonds. The most stable H-bond complex has a closed structure with two hydrogen bonds (N(7)-H^...O and O-H^...O), whereas the least stable one has an open structure with one H-bond. The interaction energies of the studied complexes are correlated to the PA and DPE involved in H-bond formation. After formation of H-bonds, the calculated IR and NMR spectra of the 2TX-water complexes change greatly, which serves to identify the hydration of 2TX.</p

High-resolution NMR structure of an RNA model system : the 14-mer cUUCGg tetraloop hairpin RNA

We present a high-resolution nuclear magnetic resonance (NMR) solution structure of a 14-mer RNA hairpin capped by cUUCGg tetraloop. This short and very stable RNA presents an important model system for the study of RNA structure and dynamics using NMR spectroscopy, molecular dynamics (MD) simulations and RNA force-field development. The extraordinary high precision of the structure (root mean square deviation of 0.3 Å) could be achieved by measuring and incorporating all currently accessible NMR parameters, including distances derived from nuclear Overhauser effect (NOE) intensities, torsion-angle dependent homonuclear and heteronuclear scalar coupling constants, projection-angle-dependent cross-correlated relaxation rates and residual dipolar couplings. The structure calculations were performed with the program CNS using the ARIA setup and protocols. The structure quality was further improved by a final refinement in explicit water using OPLS force field parameters for non-bonded interactions and charges. In addition, the 2'-hydroxyl groups have been assigned and their conformation has been analyzed based on NOE contacts. The structure currently defines a benchmark for the precision and accuracy amenable to RNA structure determination by NMR spectroscopy. Here, we discuss the impact of various NMR restraints on structure quality and discuss in detail the dynamics of this system as previously determined

Solution structure and stability of the DNA undecamer duplexes containing oxanine mismatch

Solution structures of DNA duplexes containing oxanine (Oxa, O) opposite a cytosine (O:C duplex) and opposite a thymine (O:T duplex) have been solved by the combined use of 1H NMR and restrained molecular dynamics calculation. One mismatch pair was introduced into the center of the 11-mer duplex of [d(GTGACO6CACTG)/d(CAGTGX17GTCAC), X = C or T]. 1H NMR chemical shifts and nuclear Overhauser enhancement (NOE) intensities indicate that both the duplexes adopt an overall right-handed B-type conformation. Exchangeable resonances of C17 4-amino proton of the O:C duplex and of T17 imino proton of O:T duplex showed unusual chemical shifts, and disappeared with temperature increasing up to 30°C, although the melting temperatures were >50°C. The O:C mismatch takes a wobble geometry with positive shear parameter where the Oxa ring shifted toward the major groove and the paired C17 toward the minor groove, while, in the O:T mismatch pair with the negative shear, the Oxa ring slightly shifted toward the minor groove and the paired T17 toward the major groove. The Oxa mismatch pairs can be wobbled largely because of no hydrogen bond to the O1 position of the Oxa base, and may occupy positions in the strands that optimize the stacking with adjacent bases

Characterization Of Charge Accommodation In Biologically Important Hydrogen-Bonded Clusters

The underlying motivation of chemical physics and physical chemistry is to understand naturally occurring chemical and physical processes from the nanoscopic molecular level to the macroscopic condensed phase. Over the past half-century, experimentalists have developed a number of laser-based analytical techniques to bridge the gap between the bulk phase and the single molecule. Here, we look at bulk phase and gas phase clusters to compare the local hydrogen-bonded network. To better understand the role noncovalent interactions have on biologically relevant building blocks in a natural environment, we compare the microhydration of gas phase cluster ions to condensed phase spectra. The accommodation of excess charge plays an essential character in a number of biochemical processes involving peptides, nucleobases, aerosols, etc. A time-of-flight mass spectrometer was constructed to isolate discrete numbers of solute and solvent molecules for spectroscopic interrogation via light-matter interactions. We also employed high-resolution Raman spectroscopy for vibrational interrogation of temperature dependence in crystalline lattice modes as well as effects of surface-enhanced Plasresonances. Electronic structure methods were employed for accurate spectral assignment and identification of structural motifs

Interactions of Nucleic Acid Bases with Temozolomide. Stacked, Perpendicular, and Coplanar Heterodimers

Temozolomide (TMZ) was paired with each of the five nucleic acid bases, and the potential energy surface searched for all minima, in the context of dispersion-corrected density functional theory and MP2 methods. Three types of arrangements were observed, with competitive stabilities. Coplanar H-bonding structures, reminiscent of Watson–Crick base pairs were typically the lowest in energy, albeit by a small amount. Also very stable were perpendicular arrangements that included one or more H-bonds. The two monomers were stacked approximately parallel to one another in the third category, some of which contained weak and distorted H-bonds. Dispersion was found to be a dominating attractive force, largest for the stacked structures, and smallest for the coplanar dimers

19F NMR studies of the solution structure and dynamics of 5-fluorouracil-substituted valine tRNA from Escherichia coli

Valine tRNA was purified from 5-fluorouracil (FUra) treated E. coli cells and resolved into two isoaccepting species, termed FUra tRNA(,1)(\u27Val) forms (A) and (B), respectively. The (\u2719)F NMR spectrum of the (B) form contains 13 resolved resonances for the 14 incorporated FUra residues dispersed from 1.6 and 8.5 ppm (FUra = 0 ppm). (\u2719)F NMR spectra of the (A) and (B) forms differ in the shift of peak E from ca. 4.3 ppm in form (B) upfield to ca. -15 ppm in form (A). In light of previous sequence studies with FUra tRNA(,F)(\u27Met) and (\u2719)F spectral differences between the two forms of tRNA(,1)(\u27Val), peak E in the NMR spectrum of FUra tRNA(,1)(\u27Val) (B) is assigned to F17. (\u2719)F NMR thermal denaturation, bisulfite modification, pH dependence, and Solvent Isotope Shift studies indicate that downfield NMR peaks (4.8-8.5 ppm) correspond to residues participating in tertiary structure interactions, upfield peaks (1.6-3.8 ppm) correspond to residues located in helical domains, and central-field resonances (3.9-4.5 ppm) correspond to residues in relatively unstructured environments. Thermal denaturation studies allow assignment of peak B in the (\u2719)F NMR spectrum of FUra tRNA(,1)(\u27Val) to F54 and, based on this assignment, demonstrate a thermally-induced low temperature (T(,m) = 36(DEGREES)C) structural transition to a less stacked conformation in the T(psi)C-loop region of the tRNA. Based on a conserved ca. 4 ppm upfield shift of peak A in the (\u2719)F NMR spectra of FUra tRNA(,1)(\u27Val), tRNA(,f)(\u27Met), and tRNA(,m)(\u27Met) upon removal of Mg(\u272+), peak A has been tentatively assigned to F55. (\u2719)F (\u2719)F nuclear Overhauser effect studies with 6-deutero-FUra tRNA(,1)(\u27Val) agree with and enhance the assignment of peaks A and B to F55 and F54, respectively.;(\u2719)F NMR relaxation parameters were measured and interpreted within the diffusion in a cone or two-state jump formalisms in order to derive motional amplitudes, due to pseudorotational fluctuations of the ribose ring, for the individual 5-fluorouridine (FUrd) residues in FUra tRNA(,1)(\u27Val). These motions occur on the nanosecond time scale and the amplitudes may be correlated directly with the environmental domain of the residue. The large chemical shift anisotropy contributions to the (\u2719)F linewidths indicate a maintenance of hydrogen-bonding and/or stacking interactions for all FUrd residues in FUra tRNA(,1)(\u27Val). A correlation between residue mobility and solvent exposure is also demonstrated

Experimental and computational studies of spectroscopic properties of 2-aminopurine and pyrrolocytosine

Pyrrolocytosine (Pc) and 2-aminopurine (2-Ap) are modified fluorescent nucleobases that can respectively replace the non-fluorescent natural nucleobases cytosine (C) and adenine (A) and therefore, can be used to probe the structure and dynamics of nucleic acids. Changes in fluorescence emission intensity of these modified bases as a function of polarity (general solvent effect) were measured. Lippert plots were generated and the difference between the excitation and emission maxima (Stokes shift) wavelengths of Pc and 2-Ap in water and acetonitrile mixtures indicate that the measured Stokes shifts are mainly due to hydrogen bonding (specific solvent effect) rather than polarity. The data of the quantum yield measurements show that the fluorescence intensity of 2-Ap decreases in organic solvents as opposed to that of Pc. The big difference in dipole moment of the bases in the excited and ground state experimentally found may be due to intramolecular charge transfer. Computational studies performed at DFT (Density Functional Theory) level by using the B3LYP functional revealed that the most stable 2-Ap tautomer is the N9H amino tautomer in both gas and liquid phase. In the case of Pc, our results show that the most stable tautomer in the gas phase is the N9H enol tautomer whereas the N1H N9H keto one is the most stable tautomer in solution. The theoretical absorption and emission maxima are in excellent agreement with the experimental data. The optimized geometry of 2-Ap A in the ground state was found to be non-planar, i.e., with an out of plane pyramidal amino group with respect to the purine ring whereas the optimized molecule appears to be planar in the first excited state. When 2-Ap A is explicitly bound to water molecules, the energy gap between the dark state n-π* and the bright state π-π* is bigger than the electronic energy gap between the two states previously predicted in implicit solvent. The quantum yield of 2-Ap in phosphate buffers is lower than the one measured in water. This decrease in fluorescence emission is almost certainly due to dynamic quenching. The fluorescence emission of both 2-Ap and Pc is drastically reduced when the bases are incorporated into single and double-stranded oligonucleotides but, the degree of fluorescence depression is more marked in water than in buffer solutions. Oligonucleotides may form secondary structures in buffers because of the presence of salts; in particular, G-quadruplexes. The spectroscopic data acquired by using UV, fluorescence, CD (circular dichroism), and anisotropy steady-state techniques seem to rule out the presence of G-quadruplex secondary structure in selected fluorescent nucleobase containing oligonucleotides

Studies related to primitive chemistry. A proton and nitrogen-14 nuclear magnetic resonance amino acid and nucleic acid constituents and a and their possible relation to prebiotic

Preliminary proton nuclear magnetic resonance (NMR) studies were made to determine the applicability of this technique for the study of interactions between monomeric and polymeric amino acids with monomeric nucleic acid bases and nucleotides. Proton NMR results for aqueous solutions (D2O) demonstrated interactions between the bases cytosine and adenine and acidic and aromatic amino acids. Solutions of 5'-AMP admixed with amino acids exhibited more complex behavior but stacking between aromatic rings and destacking at high amino acids concentration was evident. The multisite nature of 5'-AMP was pointed out. Chemical shift changes for adenine and 5'-AMP with three water soluble polypeptides demonstrated that significant interactions exist. It was found that the linewidth-pH profile of each amino acid is unique. It is concluded that NMR techniques can give significant and quantitative data on the association of amino acid and nucleic acid constituents