Photosensitized Thymine Dimerization via Delocalized Triplet Excited States

A new mechanism of photosensitized formation of thymine (Thy) dimers is proposed, which involves generation of a delocalized triplet excited state as the key step. This is supported by chemical evidence obtained by combining one benzophenone and two Thy units with different degrees of freedom, whereby the photoreactivity is switched from a clean Paternò–Büchi reaction to a fully chemo‐, regio‐, and stereoselective [2+2] cycloaddition.     

Light‐Controlled Histone Deacetylase (HDAC) Inhibitors: Towards Photopharmacological Chemotherapy

Cancer treatment suffers from limitations that have a major impact on the patient’s quality of life and survival. In the case of chemotherapy, the systemic distribution of cytotoxic drugs reduces their efficacy and causes severe side effects due to nonselective toxicity. Photopharmacology allows a novel approach to address these problems because it employs external, local activation of chemotherapeutic agents by using light. The development of photoswitchable histone deacetylase (HDAC) inhibitors as potential antitumor agents is reported herein. Analogues of the clinically used chemotherapeutic agents vorinostat, panobinostat, and belinostat were designed with a photoswitchable azobenzene moiety incorporated into their structure. The most promising compound exhibits high inhibitory potency in the thermodynamically less stable cis form and a significantly lower activity for the trans form, both in terms of HDAC activity and proliferation of HeLa cells. This approach offers a clear prospect towards local photoactivation of HDAC inhibition to avoid severe side effects in chemotherapy.     

A Comparison of Three Different Biodegradable Aliphatic Oligoesters (PGA,PLLA, and PCL) with Similar Linear Alkyl End Groups by DSC and SAXS

The biodegradable aliphatic oligoesters polyglycolide (PGA), poly(L-lactide) (PLLA), and poly(?-caprolactone) (PCL) with similar number-average molecular weight M_n values but different linear alkyl end groups [CH₃?[CH₂?CH₂]_m?CH₂?] were compared in terms of their physical properties, parameters such as melting temperature (T_m), crystallinity (x_i), long period (L), and lamella thickness (D). They were analyzed by DSC and SAXS. The effect of a longer and nonpolar alkyl end group such as docosyl [CH₃?[CH₂?CH₂]₁₀?CH₂?] on the long period (L) was more evident for PCL because it was the most nonpolar species in the family of oligoesters analyzed.     

Cholesterol Hydroperoxides as Substrates for Cholesterol‐Metabolizing Cytochrome P450 Enzymes and Alternative Sources of 25‐Hydroxycholesterol and other Oxysterols

The interaction of the primary autoxidation products of cholesterol, namely 25‐ and 20ξ‐hydroperoxides, with the four principal cholesterol‐metabolizing cytochrome P450 enzymes is reported. Addition of cholesterol 25‐hydroperoxide to the enzymes CYP27A1 and CYP11A1 induced well‐defined spectral changes while generating 25‐hydroxycholesterol as the major product. The 20ξ‐hydroperoxides induced spectral shifts in CYP27A1 and CYP11A1 but glycol metabolites were detected only with CYP11A1. CYP7A1 and CYP46A1 failed to give metabolites with any of the hydroperoxides. A P450 hydroperoxide‐shunt reaction is proposed, where the hydroperoxides serve as both donor for reduced oxygen and substrate. CYP27A1 was shown to mediate the reduction of cholesterol 25‐hydroperoxide to 25‐hydroxycholesterol, a role of potential significance for cholesterol‐rich tissues with high oxidative stress. CYP27A1 may participate in the removal of harmful autoxidation products in these tissues, while providing a complementary source of 25‐hydroxycholesterol, a modulator of immune cell function and mediator of viral cell entry.     

Nickel‐Catalyzed Amination of Aryl Chlorides with Ammonia or Ammonium Salts

The nickel‐catalyzed amination of aryl chlorides to form primary arylamines occurs with ammonia or ammonium sulfate and a well‐defined single‐component nickel(0) precatalyst containing a Josiphos ligand and an η²‐bound benzonitrile ligand. This system also catalyzes the coupling of aryl chlorides with gaseous amines in the form of their hydrochloride salts.     

Cooperative Bond Activation and Catalytic Reduction of Carbon Dioxide at a Group 13 Metal Center

A single‐component ambiphilic system capable of the cooperative activation of protic, hydridic and apolar H? X bonds across a Group 13 metal/activated β‐diketiminato (Nacnac) ligand framework is reported. The hydride complex derived from the activation of H₂ is shown to be a competent catalyst for the highly selective reduction of CO₂ to a methanol derivative. To our knowledge, this process represents the first example of a reduction process of this type catalyzed by a molecular gallium complex.     

Olefin‐Directed Palladium‐Catalyzed Regio‐ and Stereoselective Oxidative Arylation of Allenes

An olefin‐directed palladium‐catalyzed oxidative regio‐ and stereoselective arylation of allenes to afford 1,3,6‐trienes has been established. A number of functionalized allenes, including 2,3‐ and 3,4‐dienoates and 3,4‐dienol derivatives, have been investigated and found to undergo the olefin‐directed allene arylation. The olefin moiety has been proven to be a crucial element for the arylating transformation.     

Whole‐Genome Sequencing of a Single Viral Species from a Highly Heterogeneous Sample

Metagenomic studies suggest that only a small fraction of the viruses that exist in nature have been identified and studied. Characterization of unknown viral genomes is hindered by the many genomes populating any virus sample. A new method is reported that integrates drop‐based microfluidics and computational analysis to enable the purification of any single viral species from a complex mixed virus sample and the retrieval of complete genome sequences. By using this platform, the genome sequence of a 5243 bp dsDNA virus that was spiked into wastewater was retrieved with greater than 96 % sequence coverage and more than 99.8 % sequence identity. This method holds great potential for virus discovery since it allows enrichment and sequencing of previously undescribed viruses as well as known viruses.