Vibrational Properties of the Phosphate Group Investigated by Molecular Dynamics and Density Functional Theory

The phosphate group (PO₂^–) is an important building block occurring in many components of living matter including nucleic acids. It provides distinct features in vibrational spectra and is useful as a local probe of NA conformation and interactions with the environment. For this purpose, it is desirable to explore in detail various factors influencing spectral shapes of characteristic phosphate vibrations. In the present study, effects of the solvent and conformational averaging are analyzed for simple model molecules, dimethylphosphate, ethylmethylphosphate, and ethylmethylthiophosphate. Infrared absorption (IR) and Raman spectra were measured and calculated using a combination of molecular dynamics (MD) and density functional theory (DFT). To fully understand the link between the structure and the spectra, the solvent has to be explicitly included in the computational modeling. The results indicate that vibrational properties of the phosphate moiety are very sensitive to its conformation and interactions with the aqueous environment indeed. Polarizable continuum solvent models without explicit water molecules provided significantly worse agreement with the experiment. The combined MD/DFT approach captures well spectral characteristics for the model systems and constitutes the most reliable basis for exploration of phosphate vibrational properties in biomolecular structural studies

4‑Toluenesulfonyloxymethyl‑(<i>H</i>)‑phosphinate: A Reagent for the Introduction of <i>O</i>- and <i>S</i>‑Methyl‑(<i>H</i>)‑phosphinate Moieties

The straightforward synthesis of sodium 4-toluene­sulfonyl­oxymethyl-(<i>H</i>)-phosphinate and (<i>H</i>)-phosphino­methyl­isothio­uronium tosylate as new reagents for the preparation of <i>O</i>- and <i>S</i>-methyl-(<i>H</i>)-phosphinic acid derivatives, respectively, is described. The reactivity of both reagents was demonstrated by the preparation of protected 2′-deoxy­ribonucleo­side-<i>O</i>-methyl-(<i>H</i>)-phosphinates in the 5′- and 3′-series and 2′,5′-dideoxy­ribonucleo­side-5′-<i>S</i>-methyl-(<i>H</i>)-phosphinates. These compounds represent a new class of monomers compatible with the solid phase synthesis of oligonucleotides by <i>H</i>-phosphonate chemistry, as it was proved with the synthesis of a fully phosphonate heptamer

Straightforward Synthesis of Purine 4′-Alkoxy-2′-deoxynucleosides: First Report of Mixed Purine–Pyrimidine 4′-Alkoxyoligodeoxynucleotides as New RNA Mimics

Purine and pyrimidine 4′-alkoxy-2′-deoxynucleosides were efficiently prepared from nucleoside 4′-5′-enol acetates in three steps by <i>N</i>-iodosuccinimide promoted alkoxylation, hydrolysis, and reduction followed by conversion to phosphoramidite monomers for the solid-phase synthesis of the oligonucleotides. Fully modified 4′-alkoxyoligodeoxynucleotides, which are characterized by a prevalent <i>N</i>-type (RNA-like) conformation, exhibited superior chemical and nuclease resistance as well as excellent hybridization properties with a strong tendency for RNA-selective hybridization, suggesting a potential application of 4′-alkoxy-oligodeoxynucleotides in antisense technologies

Theoretical and Experimental Study of Charge Transfer through DNA: Impact of Mercury Mediated T‑Hg‑T Base Pair

DNA-Hg complexes may play an important role in sensing DNA defects or in detecting the presence of Hg in the environment. A fundamental way of characterizing DNA-Hg complexes is to study the way the electric charge is transferred through the molecular chain. The main goal of this contribution was to investigate the impact of a mercury metal cation that links two thymine bases in a DNA T-T mismatched base pair (T-Hg-T) on charge transfer through the DNA molecule. We compared the charge transfer efficiencies in standard DNA, DNA with mismatched T-T base pairs, and DNA with a T-Hg­(II)-T base pair. For this purpose, we measured the temperature dependence of steady-state fluorescence and UV–vis of the DNA molecules. The experimental results were confronted with the results obtained employing theoretical DFT methods. Generally, the efficiency of charge transfer was driven by mercury changing the spatial overlap of bases