Structure and Dynamics of Oligonucleotides in the Gas Phase

By combining ion‐mobility mass spectrometry experiments with sub‐millisecond classical and ab initio molecular dynamics we fully characterized, for the first time, the dynamic ensemble of a model nucleic acid in the gas phase under electrospray ionization conditions. The studied oligonucleotide unfolds upon vaporization, loses memory of the solution structure, and explores true gas‐phase conformational space. Contrary to our original expectations, the oligonucleotide shows very rich dynamics in three different timescales (multi‐picosecond, nanosecond, and sub‐millisecond). The shorter timescale dynamics has a quantum mechanical nature and leads to changes in the covalent structure, whereas the other two are of classical origin. Overall, this study suggests that a re‐evaluation on our view of the physics of nucleic acids upon vaporization is needed.     

Synthesis of Piperidine Nucleosides as Conformationally Restricted Immucillin Mimics

The de novo synthesis of piperidine nucleosides from our homologating agent 5,6-dihydro-1,4-dithiin is herein reported. The structure and conformation of nucleosides were conceived to faithfully resemble the well-known nucleoside drugs Immucillins H and A in their bioactive conformation. NMR analysis of the synthesized compounds confirmed that they adopt an iminosugar conformation bearing the nucleobases and the hydroxyl groups in the appropriate orientation.     

Determination of Hyaluronic Acid in a Chitosan-Based Formulation by RP C18 and HILIC LC–ESI-MS: an Evaluation of Matrix Effect

Two simple and fast C18 and HILIC liquid chromatography–electrospray mass spectrometry methods for the determination of hyaluronic acid (HA) in a mucoadhesive chitosan-based formulation were developed and validated. The performances of both methods were compared in terms of validation parameters and matrix effect. A simple sample preparation method based on sulphuric acid-based degradation was optimized for the detection of HA fragments (i.e. m/z 380 2-mer, m/z 759 4-mer, m/z 1,138 8-mer and m/z 1,518 16-mer). By operating under selected ion-monitoring mode, excellent selectivity towards chitosan fragments was obtained. For validation, good linearity, detection limits (<4 μg mL⁻¹) and precision (RSD % < 16 %) were generally obtained on matrix with both columns. However, HILIC column exhibited improved performances in terms of HA fragment separation and selectivity. By analyzing on the C18 column the chitosan-based formulation and sample extracts from pig mucosa treated with the formulation, matrix effects exhibited a dependence of signal suppression degree (ranging from 37 to 83 %) as a function of the HA fragment dimension. The HILIC column afforded instead a significantly reduced suppression degree (ranging from 1 to 16 %) and a better separation. These findings demonstrated the improved performances of the HILIC column with respect to conventional C18 mechanism for the analysis of HA fragments in complex matrices.

     

Infrared Problem for the Nelson Model on Static Space-Times

We consider the Nelson model on some static space-times and investigate the problem of existence of a ground state. Nelson models with variable coefficients arise when one replaces in the usual Nelson model the flat Minkowski metric by a static metric, allowing also the boson mass to depend on position. We investigate the existence of a ground state of the Hamiltonian in the presence of the infrared problem, i.e. assuming that the boson mass m(x) tends to 0 at spatial infinity. We show that if m(x) ≥ C |x|⁻¹ at infinity for some C > 0 then the Nelson Hamiltonian has a ground state.