Emerging avenues for the management of cerebral malaria.

OBJECTIVES: Cerebral malaria (CM) is a lethal complication of Plasmodium falciparum infection. The multifactorial pathogenesis of the disease involving parasitic invasion of erythrocytes and sequestration of infected erythrocytes within the cerebral blood vessels leading to neuroinflammation and blood-brain barrier (BBB) disruption demands a multi-pronged treatment strategy. This article gives a brief overview of the pathogenesis of CM, challenges associated with its treatment and potential strategies to combat the same. KEY FINDINGS: There are several roadblocks in the successful treatment of CM. Resistance to artemisinin-based therapies has been reported in malaria-endemic regions. The paucity of targeted delivery to the brain necessitates the administration of antimalarials such as quinine in large doses causing toxic effects. There is a need for compounds to prevent oxidative stress, neuroinflammation and BBB disruption to decrease the menace of neurological sequelae associated with CM. SUMMARY: Extensive research endeavours are now oriented towards investigating compounds that can act against neuroinflammation; developing brain-targeted nanocarriers to selectively deliver therapeutics against CM; and repurposing existing drugs and a combination of antimalarial and anti-inflammatory or immunomodulatory molecules for the treatment of CM. Protocols for evaluating novel proposed therapies against CM should be revisited to integrate monitoring of neurological parameters in parallel with the estimation of parasite load and survival.

Hydrogen-Generating Ru/Pt Bimetallic Photocatalysts Based on Phenyl-Phenanthroline Peripheral Ligands.

Recent studies on hydrogen-generating supramolecular bimetallic photocatalysts indicate a more important role of the peripheral ligands than expected, motivating us to design a Ru/Pt complex with 4,7-diphenyl-1,10-phenanthroline peripheral ligands. Photoinduced intra- and inter-ligand internal conversion processes have been investigated using transient absorption spectroscopy, spanning the femto- to nanosecond timescale. After photoexcitation and ultrafast intersystem crossing, triplet states localised on either the peripheral ligands or on the bridging ligand/catalytic unit are populated in a non-equilibrated way. Time-resolved photoluminescence demonstrates that the lifetime for the Ru/Pt dinuclear species (795±8 ns) is significantly less than that of the mononuclear analogue (1375±20 ns). The photocatalytic studies show modest hydrogen turnover numbers, which is possibly caused by the absence of an excited state equilibrium. Finally, we identify challenges that must be overcome to further develop this class of photocatalysts and propose directions for future research.

Mild synthesis of silyl ethers via potassium carbonate catalyzed reactions between alcohols and hydrosilanes.

A method has been developed for the silanolysis of alcohols using an abundant and non-corrosive base K2CO3 as a catalyst. Reactions between a variety of alcohols and hydrosilanes generate silyl ethers under mild conditions. The use of hydrosilanes leads to the formation of H2 as the only byproduct thus avoiding the formation of stoichiometric strong acids. The mild conditions lead to a wide scope of possible alcohol substrates and good functional group tolerance. Selective alcohol silanolysis is also observed in the presence of reactive C-H bonds, lending this method for extensive use in protection group chemistry.

Enhancing Photocatalytic Hydrogen Generation: the Impact of the Peripheral Ligands in Ru/Pd and Ru/Pt Complexes.

The synthesis, photophysical properties and photocatalytic efficiency of a range of novel supramolecular assemblies of the type [Ru(dceb)2 (µ-bisbpy)MCl2 ][PF6 ]2 and [Ru(bpy)2 (µ-bisbpy)MCl2 ][PF6 ]2 (M=Pd or Pt, dceb=diethyl 2,2'-bipyridine-4,4'-dicarboxylate, bpy=2,2'-bipyridine and bisbpy=2,2':5',3'':6'',2'''-quaterpyridine) are reported. Photocatalytic hydrogen generation was dependent on the nature of the peripheral ligand, on the catalytic centre and on the amount of water present in the photocatalytic mixture. The best catalytic conditions were obtained with the dceb peripheral ligand (turnover numbers up to 513 after 18 h). The experimental data and DFT calculations on both the bpy- and dceb-based compounds indicated that the peripheral dceb ligands participated in the photocatalytic process.

Carboxy derivatised Ir(III) complexes: synthesis, electrochemistry, photophysical properties and photocatalytic hydrogen generation.

In this contribution the synthesis and characterisation of a series of novel mixed ligand iridium(iii) complexes, functionalised with a carboxy ester or phosphonate groups are reported. These groupings are introduced on the 4-position of either the phenyl pyridine or the 2,2'-bipyridyl ligands. A low temperature high yield synthesis for the precursor [Ir(ppy-COOEt)2(µ-Cl)]2 was developed. The photophysical and electrochemical properties of these compounds are also described, together with their behaviour as photosensitisers for the generation of hydrogen from water.