Strategies to control humidity sensitivity of azobenzene isomerisation kinetics in polymer thin films.

Azobenzenes are versatile photoswitches that garner interest in applications ranging from photobiology to energy storage. Despite their great potential, transforming azobenzene-based discoveries and proof-of-concept demonstrations from the lab to the market is highly challenging. Herein we give an overview of a journey that started from a discovery of hydroxyazobenzene's humidity sensitive isomerisation kinetics, developed into commercialization efforts of azobenzene-containing thin film sensors for optical monitoring of the relative humidity of air, and arrives to the present work aiming for better design of such sensors by understanding the different factors affecting the humidity sensitivity.

Azobenzene Photoswitching with Near-Infrared Light Mediated by Molecular Oxygen.

Efficient photoisomerization between the cis and the trans states of azobenzenes using low-energy light is desirable for a range of applications in, e.g., photobiology yet challenging to accomplish directly with modified azobenzenes.

Halogen bonding stabilizes a cis-azobenzene derivative in the solid state: a crystallographic study.

Crystals of trans- and cis-isomers of a fluorinated azobenzene derivative have been prepared and characterized by single-crystal X-ray diffraction. The presence of F atoms on the aromatic core of the azobenzene increases the lifetime of the metastable cis-isomer, allowing single crystals of the cis-azobenzene to be grown. Structural analysis on the cis-azobenzene, complemented with density functional theory calculations, highlights the active role of the halogen-bond contact (N.

Benchmarking DFT methods with small basis sets for the calculation of halogen-bond strengths.

In recent years, halogen bonding has become an important design tool in crystal engineering, supramolecular chemistry and biosciences. The fundamentals of halogen bonding have been studied extensively with high-accuracy computational methods. Due to its non-covalency, the use of triple-zeta (or larger) basis sets is often recommended when studying halogen bonding.

Efficient Light-Induced Phase Transitions in Halogen-Bonded Liquid Crystals.

Here, we present a new family of light-responsive, fluorinated supramolecular liquid crystals (LCs) showing efficient and reversible light-induced LC-to-isotropic phase transitions. Our materials design is based on fluorinated azobenzenes, where the fluorination serves to strengthen the noncovalent interaction with bond-accepting stilbazole molecules, and increase the lifetime of the -form of the azobenzene units. The halogen-bonded LCs were characterized by means of X-ray diffraction, hot-stage polarized optical microscopy, and differential scanning calorimetry.

A Developability-Focused Optimization Approach Allows Identification of in Vivo Fast-Acting Antimalarials: N-[3-[(Benzimidazol-2-yl)amino]propyl]amides.

Malaria continues to be a major global health problem, being particularly devastating in the African population under the age of five. Artemisinin-based combination therapies (ACTs) are the first-line treatment recommended by the WHO to treat Plasmodium falciparum malaria, but clinical resistance against them has already been reported. As a consequence, novel chemotypes are urgently needed.

Synthesis and biological evaluation of 2-arylbenzimidazoles targeting Leishmania donovani.

A set of 56 2-arylbenzimidazoles was designed, synthesized and tested against Leishmania donovani amastigotes. The left- and right-hand side rings of the molecule, as well as the amide linker were modified. Structurally different derivatives were screened on L.

Conformation study of 2-arylbenzimidazoles as inhibitors of Chlamydia pneumoniae growth.

Chlamydia pneumoniae is a worldwide cause of various respiratory track diseases ranging from asymptomatic pharyngeal infection to severe, sometimes fatal pneumonia. We have previously identified 2-arylbenzimidazoles as highly active antichlamydial compounds. In this work the importance of conformational effects on the structure-activity relationship of these compounds was studied.

Design and synthesis of 2-arylbenzimidazoles and evaluation of their inhibitory effect against Chlamydia pneumoniae.

Chlamydia pneumoniae is an intracellular bacterium that responds poorly to antibiotic treatment. Insufficient antibiotic usage leads to chronic infection, which is linked to disease processes of asthma, atherosclerosis, and Alzheimer's disease. The Chlamydia research lacks genetic tools exploited by other antimicrobial research, and thus other approaches to drug discovery must be applied.

Inhibitory effect of the natural product betulin and its derivatives against the intracellular bacterium Chlamydia pneumoniae.

Chlamydia pneumoniae is a universal pathogen that has been indicated to play a part in the development of asthma, atherosclerosis and lung cancer. The complete eradication of this intracellular bacterium is in practice impossible with the antibiotics that are currently in use and studies on new antichlamydial compounds is challenging because Chlamydia research lacks the tools required for the genetic modification of this bacterium. Betulin is a natural lupane-class triterpene derived from plants with a wide variety of biological activities.

Pharmacological characterization of noroxymorphone as a new opioid for spinal analgesia.

Background: Noroxymorphone is one of the major metabolites of oxycodone. Although oxycodone is commonly used in the treatment of acute and chronic pain, little is known about the antinociceptive effects of noroxymorphone. We present an in vivo pharmacological characterization of noroxymorphone in rats.

Eudismic analysis of tricyclic sesquiterpenoid alcohols: lead structures for the design of potent inhibitors of the human UDP-glucuronosyltransferase 2B7.

The epimeric tricyclic sesquiterpenoid alcohols globulol, epiglobulol, cedrol, epicedrol, longifolol, and isolongifolol were investigated in their ability to inhibit the recombinant human UDP-glucuronosyltransferase (UGT) 2B7. The stereoisomers displayed rapidly reversible competitive inhibition, which was substrate-independent. Longifolol and its stereoisomer isolongifolol displayed the lowest competitive inhibition constants (K(ic)) of 23 and 26 nM, respectively.

Potent inhibitors of the human UDP-glucuronosyltransferase 2B7 derived from the sesquiterpenoid alcohol longifolol.

The tricyclic sesquiterpenol (+)-longifolol served as a lead structure for the design of inhibitors of the human UDP-glucuronosyltransferase (UGT) 2B7. Twenty-four homochiral and epimeric longifolol derivatives were synthesized and screened for their ability to inhibit the enzyme. The absolute configuration at the stereogenic center C1' was determined by X-ray crystallography and 2D NMR spectroscopy (gHSQC, gNOESY).

Isoform-selective inhibition of the human UDP-glucuronosyltransferase 2B7 by isolongifolol derivatives.

A set of 48 derivatives of the tricyclic sesquiterpenol alcohol isolongifolol was synthesized. The set comprised homochiral and diastereomeric alcohols, amines, chlorohydrins, as well as carboxylic acids, phosphonic acids, and their corresponding esters. The absolute configuration of the epimeric compounds was assigned by 2D NMR experiments [gradient heteronuclear single quantum correlation (gHSQC) and gradient nuclear Overhauser enhancement spectroscopy (gNOESY)] in agreement with crystallographic data.

Antinociception by spinal and systemic oxycodone: why does the route make a difference? In vitro and in vivo studies in rats.

Background: The pharmacology of oxycodone is poorly understood despite its growing clinical use. The discrepancy between its good clinical effectiveness after systemic administration and the loss of potency after spinal administration led the authors to study the pharmacodynamic effects of oxycodone and its metabolites using in vivo and in vitro models in rats.

Methods: Male Sprague-Dawley rats were used in hot-plate, tail-flick, and paw-pressure tests to study the antinociceptive properties of morphine, oxycodone, and its metabolites oxymorphone and noroxycodone.

Chiral distinction between the enantiomers of bicyclic alcohols by UDP-glucuronosyltransferases 2B7 and 2B17.

The stereoselective binding and transformation of optically pure bicyclic alcohols by human UDP-glucuronosyltransferases from subfamily 2B were investigated. The enantiomers of 1-indanol, 1-tetralol, and 1-benzosuberol were synthesized by asymmetric Corey-Bakshi-Shibata reduction and subjected to glucuronidation assays. The alcohols studied were primarily glucuronidated by UGT2B7 and UGT2B17.

Similarity based virtual screening: a tool for targeted library design.

High throughput screening drug discovery utilizes large and expensive compound libraries. As an alternative, a smaller targeted library can be constructed with the aid of the 3D structure of the target molecule. We used the X-ray crystal structure of a protein homologous to the selected target in creation of a small focused library and evaluated inhibition potential of this library against Chlamydia pneumoniae, a common pathogen recently linked to atherosclerosis and risk of myocardial infarction.

Stereochemical sensitivity of the human UDP-glucuronosyltransferases 2B7 and 2B17.

A set of 28 enantiomers comprising rigid and flexible secondary alcohols was synthesized by the asymmetric Corey-Bakshi-Shibata reduction. The enantiomerically pure alcohols were subjected to enzymatic glucuronidation assays employing the human UDP-glucuronosyltransferases (UGTs) 2B7 and 2B17. Both UGTs displayed high levels of stereoselectivity, favoring the conjugation of the (R)-enantiomers over their respective (S)-stereoisomers at eudismic ratios up to 256.