Acyclic nucleoside phosphonates with unnatural nucleobases,favipiravir and allopurinol,designed as potential inhibitors of the human and Plasmodium falciparum 6-oxopurine phosphoribosyltransferases

Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) is a key enzyme of the purine salvage pathway and its activity is crucial for the survival of certain parasites e.g. Plasmodium falciparum (Pf). Acyclic nucleoside phosphonates (ANPs) containing either guanine or hypoxanthine as the purine base are inhibitors of this enzyme. In this part of a SAR study, these two naturally-occurring nucleobases attached to an acyclic moiety were replaced by allopurinol or favipiravir. Both allopurinol and favipiravir ANPs were prepared via Mitsunobu reaction. The alkylation of favipiravir was optimized to yield both N- and O- regioisomers but the N-regioisomers were unstable under deprotection conditions. Thus, only the ANPs containing the O-isomer of favipiravir and those containing allopurinol were evaluated as potential inhibitors of human HGPRT and PfHGXPRT. Two ANPs with allopurinol as the base have K_i values of 10?μM and 30?μM for PfHGXPRT but do not inhibit human HGPRT activity at concentrations of 100–150?μM.     

An efficient microwave-assisted synthesis and biological properties of polysubstituted pyrimidinyl- and 1,3,5-triazinylphosphonic acids

Polysubstituted pyrimidinylphosphonic and 1,3,5-triazinylphosphonic acids with potential biological properties were prepared in high yields by the microwave-assisted Michaelis–Arbuzov reaction of trialkyl phosphite with the corresponding halopyrimidines and halo-1,3,5-triazines, respectively, followed by the standard deprotection of the phosphonate group using TMSBr in acetonitrile. 4,6-Diamino-5-chloropyrimidin-2-ylphosphonic acid (7a) was found to exhibit a weak to moderate anti-influenza activity (28–50 μM) and may represent a novel hit for further SAR studies and antiviral improvement.     

Yb3+ as an origin of the strong anti-Stokes luminescence in NIR FT-Raman spectra of some lanthanide sesquioxides

Strong anti-Stokes bands observed in FT-Raman spectra of Y2O3, Gd2O3 and Lu2O3 are explained by NIR luminescence of Yb3+ impurities present in sesquioxides after the excitation with the 1064 nm line of an Nd:YAG laser. Samples of Y2O3:Yb, Ga2O3:Yb, CeO2:Yb, Gd2O3:Yb and Lu2O3:Yb were prepared by solution combustion synthesis procedure using urea. All materials were investigated by FT-Raman and FT-NIR spectroscopy and characterized by X-ray powder diffraction.     

Polysubstituted 5‐Phenylazopyrimidines: Extremely Fast Non‐ionic Photochromic Oscillators

Photochromic systems with an ultrahigh rate of thermal relaxation are highly desirable for the development of new efficient photochromic oscillators. Based on DFT calculations, we designed a series of 5‐phenylazopyrimidines with strong push–pull character in silico and observed very low energy barriers for the thermal (Z)‐to‐(E) isomerization. The structure of the (Z)‐isomer of the slowest isomerizing derivative in the series was confirmed by NMR analysis with in situ irradiation at low temperature. The substituents can tune the lifetime of thermal back isomerization from hundreds of microseconds to several nanoseconds (8 orders of magnitude). The photoswitching parameters were extracted from transient absorption techniques and a dominant rotation mechanism of the (Z)‐to‐(E) thermal fading was proposed based on DFT calculations.     

Surface-enhanced Raman study of the interactions between tripodal cationic polyamines and polynucleotides

Raman and surface-enhanced Raman spectra of new DNA/RNA-binding compounds consisting of three imidazole (Im) and three pyridine (Py) rings connected by tripodal polyaminomethylene linkages were obtained by the near-infrared excitation at 1064 nm. Study of interactions of Im and Py polyamines with single-stranded RNA polynucleotides (poly?A, poly?G, poly?C, poly?U), double-stranded DNA polynucleotides (poly?dAdT-poly?dAdT, poly?dGdC-poly?dGdC) and calf thymus DNA (ct-DNA) by surface-enhanced Raman spectroscopy (SERS) reveals unambiguous enhancement of the Raman scattering from the small molecules as well as appearance of new bands in spectra associated mainly with nucleobases. The SERS experiments point toward comparable interactions of Im and Py polyamines with single-stranded purine and pyrimidine polynucleotides. Furthermore, SERS experiments with double stranded polynucleotides reveal the base-pair dependent selectivity of Im and Py, whereby interactions within both, major and minor groove are indicated for poly?dAdT-poly?dAdT, at variance to preferred binding of Im and Py to only major groove of poly?dGdC-poly?dGdC. SERS spectra of Im and Py with ct-DNA imply that protonated amino groups of these compounds preferentially interact with N7 atoms (adenine, guanine) while nitrogen in aromatic rings of polyamines might be attracted to C6-NH(2) (adenine), all sites being located at the major groove of the DNA helix. Wavenumber downshift of the imidazole (Im) and pyridine (Py) ring vibrations supports aromatic stacking interactions of imidazole and pyridine aromatic moieties with DNA base-pairs.     

The efficient synthesis of 2-arylpyrimidine acyclic nucleoside phosphonates using Liebeskind-Srogl cross-coupling reaction

A series of novel acyclic nucleoside phosphonates with various aryls attached to the C-2 position of the pyrimidine moiety has been prepared using the Liebeskind-Srogl cross-coupling protocol. The reactions of highly functionalised 2-(methylsulfanyl)pyrimidines with various arylboronic acids were studied and optimised.     

Surface-enhanced Raman scattering on molecular self-assembly in nanoparticle-hydrogel composite

Surface-enhanced Raman scattering has been applied to study weak intermolecular interactions between small organic gelling molecules involved in the silver nanoparticle-hydrogel composite formation. Assembly and disassembly of the gelator molecules in close vicinity to embedded silver nanoparticles were followed by changes in Raman intensity of the amide II and carboxyl vibrational bands, whereas the strength of the bands related to benzene modes remained constant. This implied that the gelator molecules were strongly attached to the silver particles through the benzene units, while participating in gel structure organization by intermolecular hydrogen bonding between oxalyl amide and carboxyl groups.     

Restoration of the magnetic hc/e-periodicity in unconventional superconductors

We consider the energy of the filled quasiparticle's Fermi sea of a macroscopic superconducting ring threaded by an hc/2e vortex, when the material of the ring is of an unconventional pairing symmetry. The energy relative to the one for the hc/e vortex configuration is finite, positive, and inversely proportional to the ring's inner radius. We argue that the existence of this energy in unconventional superconductors removes the commonly assumed degeneracy between the odd and the even vortices, with the loss of the concomitant hc/2e-periodicity in an external magnetic field as a consequence. This macroscopic quantum effect should be observable in nanosized unconventional superconductors with a small phase stiffness, such as deeply underdoped YBCO with Tc<5 K.     

HF dimer in small helium clusters: interchange-tunneling dynamics in a quantum environment

We present diffusion quantum Monte Carlo calculations of the interchange tunneling splitting of (4)He(n)(HF)(2) clusters, n = 1-10. The tunneling splitting decreases rapidly for n = 1-4 clusters, and much more slowly for n>4. The decrease calculated for (4)He(n)(HF)(2) represents 74% of the reduction in the tunneling splitting measured recently for HF dimer in nanodroplets of more than 2000 He atoms. The first four He atoms quench the interchange tunneling very efficiently by virtue of occupying the equatorial ring which encircles the C(2h) transition state of the tunneling pathway.     

Charge modulation, spin response, and dual Hofstadter butterfly in high-Tc cuprates

The modulated density of states observed in recent STM experiments in underdoped cuprates is argued to be a manifestation of the charge-density wave of Cooper pairs (CPCDW). CPCDW formation is due to superconducting phase fluctuations enhanced by Mott-Hubbard correlations near half-filling. The physics behind the CPCDW is related to a Hofstadter problem in a dual superconductor. It is shown that CPCDW does not impact nodal fermions at the leading order. An experiment is proposed to probe coupling of the CPCDW to the spin carried by nodal quasiparticles.