transoid and cisoid Conformations in Silver-Mediated Cytosine Base Pairs: Hydrogen Bonding Dictates Argentophilic Interactions in the Solid State.

We have synthesized and structurally characterized examples of the well-known silver-mediated DNA base pair in its simplest possible form, as [AgI-bis-(N3-cytosine)]+. The compounds show differences such as variable coordination geometry, conformation with cisoid and transoid arrangements, and, in one case, intramolecular base pairing. Collectively, these compounds represent three of five permutations of linear/bent coordination geometry and cisoid/transoid arrangement of the cytosine ligands and contain the global minimum conformation as determined by DFT calculations: bent-transoid. Furthermore, these compounds show no argentophilic intercomplex interactions in the solid state, in marked contrast to alkylated and nucleoside analogues, and so do not form the supramolecular 1D "metallo-DNA" duplex observed in those cases but instead form hydrogen-bonded sheets. This marked difference may be attributed, in part, to the additional hydrogen bond donor site at N1 of the nucleobase that ubiquitously participates in intermolecular interactions.

Evolution of the burden of active hepatitis C virus infection in England from September 2015 to September 2016: a repeated cross-sectional analysis.

OBJECTIVE: To evaluate the impact of treatment with new direct-acting antivirals (DAAs) on the prevalent hepatitis C virus (HCV) population in England. DESIGN: A repeated cross-sectional analysis. SETTING: Four secondary care hospitals in England. PARTICIPANTS: Patients who, in 2015 and/or 2016, had chronic HCV infection and were alive were eligible, regardless of the type of HCV intervention received. OUTCOME MEASURES: Data including intravenous drug use (IVDU) status, HCV genotype, cirrhosis status, HCV treatment history, vital status and treatment outcomes were collected at two time points in 2015 and 2016 using electronic case report forms. RESULTS: There were 1605 and 1355 patients with active chronic HCV in 2015 and 2016, respectively. Between 2015 and 2016, the proportion of patients with current IVDU increased (10.3% vs 14.5%, respectively), while that of patients with cirrhosis (28.2% vs 22.4%) and treatment-experienced patients (31.2% vs 27.1%) decreased. Among patients whose treatment outcome was known by 2016, high cure rates were observed, with an overall sustained virological response rate of 93.2%. From 2015 to 2016, there was a progressive increase in the proportion of treated patients who were non-cirrhotic, with current IVDU and non-liver transplant recipients. CONCLUSIONS: The characteristics of patients with HCV remaining in contact with specialised care evolved with a changing landscape of treatment and related health policy. With increasing access to DAAs in UK, high cure rates were achieved in the study cohort.

Addressing the properties of "Metallo-DNA" with a Ag(i)-mediated supramolecular duplex.

The silver-nucleoside complex [Ag(i)-(N3-cytidine)2], 1, self-assembles to form a supramolecular metal-mediated base-pair array highly analogous to those seen in metallo-DNA. A combination of complementary hydrogen-bonding, hydrophobic and argentophilic interactions drive the formation of a double-helix with a continuous silver core. Electrical measurements on 1 show that despite having Ag···Ag distances within <5% of the metallic radii, the material is electrically insulating. This is due to the electronic structure which features a filled valence band, an empty conduction band dominated by the ligand, and a band gap of 2.5 eV. Hence, as-prepared, such Ag(i)-DNA systems should not be considered molecular nanowires but, at best, proto-wires. The structural features seen in 1 are essentially retained in the corresponding organogel which exhibits thixotropic self-healing that can be attributed to the reversible nature of the intermolecular interactions. Photo-reduced samples of the gel exhibit luminescence confirming that these poly-cytidine sequences appropriately pre-configure silver ions for the formation of quantum-confined metal clusters in line with contemporary views on DNA-templated clusters. Microscopy data reveals the resulting metal cluster/particles are approximately spherical and crystalline with lattice spacing (111) similar to bulk Ag.