Deciphering Internal and External π-Conjugation in C3 -Symmetric Multiple Azobenzene Connected Systems in Self-Assembly.

Two tripodal C3 -symmetric photoswitchable molecular systems T1 and T2 are reported that have extended conjugation at external and internal positions using an acryl group. The influence of the extended π-bonds in their absorption properties, thermal relaxation of the photoisomers and their propensities in forming supramolecular self-assemblies have been explored through spectroscopy, and microscopic studies. In particular, the investigations on the self-assembly have been carried out using scanning electron microscopy (SEM), transmission electron microscopy (TEM), polarized optical microscopy (POM), X-ray diffraction studies (XRD) and atomic force microscopy (AFM). Remarkably, the position of the acryl group influences the behaviour of the two target molecules in supramolecular assembly, and also in the formation of photoresponsive organic hydrogels or microcrystals.

Tuning of Bistability, Thermal Stability of the Metastable States, and Application Prospects in the C3 -Symmetric Designs of Multiple Azo(hetero)arenes Systems.

Light-responsive molecular systems with multiple photoswitches in C3 -symmetric designs have enormous application potential. The design part of such molecular systems is critical due to its influence in several properties associated with the photoswitches. In order to tune, and in the evaluation of the design-property relationship, we synthesized 18 tripodal systems with variations in the core, linkers, connectivity, and azo(hetero)arene photoswitches. Through extensive spectroscopic and computational studies, we envisaged the factors controlling near-quantitative photoisomerization in both the directions (bistability) and the thermal stability of the metastable states. Furthermore, we also evaluated the impact of designs in obtaining reversible photo-responsive sol-gel phase transitions, solvatochromism, photo- and thermochromism.

Metal Compounds against Neglected Tropical Diseases.

Many first-line treatments for neglected tropical diseases identified by the World Health Organization (WHO) are limited by one or more of the following: the development of drug resistance, toxicity, and side effects, lack of selectivity, narrow therapeutic indices, route of administration, and bioavailability. As such, there is an urgent need to develop viable alternatives to overcome these limitations. The following review provides an overview of all existing metal complexes studied and evaluates the status of these complexes on the respective disease of choice.

Increased Lipophilicity of Halogenated Ruthenium(II) Polypyridyl Complexes Leads to Decreased Phototoxicity in†vitro when Used as Photosensitizers for Photodynamic Therapy.

In the fight against cancer, photodynamic therapy is generating great interest thanks to its ability to selectively kill cancer cells without harming healthy tissues. In this field, ruthenium(II) polypyridyl complexes, and more specifically, complexes with dipyrido[3,2-a:2',3'-c]phenazine (dppz) as a ligand are of particular interest due to their DNA-binding and photocleaving properties. However, ruthenium(II) polypyridyl complexes can sometimes suffer from low lipophilicity, which hampers cellular internalisation through passive diffusion. In this study, four new [Ru(dppz-X2 )3 ]2+ complexes (X=H, F, Cl, Br, I) were synthesized and their lipophilicity (logP), cytotoxicity and phototoxicity on cancerous and noncancerous cell lines were assessed. This study shows that, counterintuitively, the phototoxicity of these complexes decreases as their lipophilicity increases; this could be due solely to the atomic radius of the halogen substituents.

The benzylperoxyl radical as a source of hydroxyl and phenyl radicals.

The benzyl radical (1) is a key intermediate in the combustion and tropospheric oxidation of toluene. Because of its relevance, the reaction of 1 with molecular oxygen was investigated by matrix-isolation IR and EPR spectroscopy as well as computational methods. The primary reaction product of 1 and O2 is the benzylperoxyl radical (2), which exists in several conformers that can easily interconvert even at cryogenic temperatures. Photolysis of radical 2 at 365 nm results in a formal [1,3]-H migration and subsequent cleavage of the O-O bond to produce a hydrogen-bonded complex between the hydroxyl radical and benzaldehyde (4). Prolonged photolysis produces the benzoyl radical (5) and water, which finally yield the phenyl radical (7), CO, and H2O. Thus, via a sequence of exothermic reactions 1 is transformed into radicals of even higher reactivity, such as OH and 7. Our results have implications for the development of models for the highly complicated process of combustion of aromatic compounds.

Interactions of aromatic radicals with water.

The interactions of the benzyl radical (1), the anilinyl radical (2), and the phenoxyl radical (3) with water are investigated using density functional theory (DFT). In addition, we report dispersion-corrected DFT-D molecular dynamics simulations on these three systems and a matrix isolation study on 1-water. The radicals 1-3 form an interesting series with the number of lone pairs increasing from none to two. The anilinyl and benzyl radicals can act as Lewis base through their unpaired electrons, the lone pairs of the heteroatoms, or the doubly occupied π orbitals of the aromatic system. Matrix isolation experiments provide evidence for the formation of a π complex between 1 and water. By combining computational and experimental techniques we identify the possible interactions between the aromatic radicals 1-3 and water, predict the structure and vibrational spectra of the resulting complexes, and analyze the effects of substitution and temperature.

The phenoxyl radical-water complex--a matrix isolation and computational study.

The phenoxyl radical 1 was generated in high yields by flash vacuum pyrolysis of allyl phenyl ether 2 with subsequent trapping of the products in argon at 3 K. In water-doped argon matrices, an OH···O complex between 1 and water is formed that could be characterized by IR spectroscopy. Several isotopomers of the complex were generated, and the IR spectra compared to results of density functional theory calculations. Other dimers between 1 and water were not found under these conditions. QM/MM calculations in simulated argon matrices reveal that an OH···π complex is unstable even at a time scale of picoseconds. This finding has implications on the related interaction between the tyrosyl radical and the water in biological systems.

Ferrocenyl, Ruthenocenyl, and Benzyl Oxamniquine Derivatives with Cross-Species Activity against Schistosoma mansoni and Schistosoma haematobium.

Schistosomiasis is a parasitic disease that affects more than 250 million people annually, mostly children in poor, tropical, rural areas. Only one treatment (praziquantel) is available, putting control efforts at risk should resistance occur. In pursuit of treatment alternatives, we derivatized an old antischistosomal agent, oxamniquine (OXA). Four organometallic derivatives of OXA were synthesized and tested against Schistosoma mansoni in vitro and in vivo. Of these, a ferrocenyl derivative, 1, killed larval and adult worms 24 h postexposure in vitro, in contrast to OXA, which lacks in vitro activity against adult worms. A dose of 200 mg/kg of 1 completely eliminated the worm burden in mice. Subsequently, a ruthenocenyl (5) and a benzyl derivative (6) of OXA were synthesized to probe the importance of the ferrocenyl group in 1. Compounds 1, 5, and 6 were lethal to both S. mansoni and S. haematobium adults in vitro. In vivo, at 100 mg/kg, all three compounds revealed S. mansoni worm burden reductions of 76 to 93%, commensurate with OXA. Our findings present three compounds with activity against S. mansoni in vitro, comparable activity in vivo, and high activity against S. haematobium in vitro. These compounds may possess a different binding mode or mode of action compared to OXA and present excellent starting points for further SAR studies.