Luminescent Cyclometallated Ir(III) Complexes: Synthesis, Characterisation and Applications

A range of luminescent Ir(III) complexes [Ir(C^N)2(X^Y)]n+ (n = 0, 1) containing different cyclometallated (C^N) and ancillary (X^Y) ligands has been synthesised. All new compounds were fully characterised by 1H and 13C NMR spectroscopy, mass spectrometry and elemental analyses and several compounds have been structurally characterised by X-ray crystallography. The photophysical and electrochemical properties of the complexes were also studied. Chapter one provides an introduction to luminescent transition metal complexes, in particular Ru(II) and Ir(III) complexes and gives an overview of the factors controlling the emission wavelengths of cyclometallated Ir(III) complexes and their applications, particularly as biological labels and probes. Chapter two discusses the synthesis and properties of [Ir(C^N)2(bipy)]+ and shows that substituents para to the metal on the cyclometallated phenyl have a significant effect on the emission wavelength. Chapter three describes complexes [Ir(C^N)2(X^Y)]n+ (n = 1, X^Y = pyridine imine; n = 0, X^Y = pyrrolylimine) and the effect of substituents on the redox properties and emission wavelength. Some of these complexes have been employed in live-cell imaging. In Chapter four the synthesis, characterisation and application of [Ir(C^N)2(phencat-OH)]+ complexes as molybdate sensors is discussed. Chapter five describes the synthesis of [Ir(C^N)2(X^Y)]n+ (n = 0, 1) containing a homochiral X^Y ligand i.e. (S)-soxH, (S)-pepH, (S)-phglyH, (+)-tfacH and (S)-ppea. The complexes are all formed as 1:1 mixtures of diastereomers with Δ or Λ chirality at the metal. Diastereomers containing the (S)-sox and (S)-pep ligands can often be separated via crystallisation or column chromatography. Treatment of a single diastereomer (ΛS or ΔS) with an appropriate acid removes the sox or pep ligand hence provides a route to complexes with only metal-centred chirality, for example Λ- and Δ-[Ir(ppz)2(bipy)]+

Protein-protein interaction diagram of annotated proteins up regulated above 1.5 fold and down regulated below 0.9 fold with ANOVA value less than 0.05.

Protein-protein interactions between the proteins were analyzed by using STRING database. Here the thickness of the lines represents the strength of the association between two proteins. The mode of interaction of each protein is represented by different colours. Also, the directionality of action is represented by the presence of dots at the end of connecting lines.</p

Coexpression analysis of different proteins form the protein-protein interaction network.

<p>The coexpression analysis was performed by using STRING based on the data available from different species including <i>O</i>. <i>sativa</i>, <i>A</i>. <i>thaliana</i>, <i>S</i>. <i>cerevisiae</i>, <i>M</i>. <i>musculus</i>, <i>P</i>. <i>falciparum</i>, <i>D</i>. <i>melanogaster</i>, <i>C</i>. <i>elegans</i>, <i>D</i>. <i>rerio</i>, <i>G</i>. <i>gallus</i>, <i>S</i>. <i>pombe</i>, <i>M</i>. <i>mulatta</i>, <i>R</i>. <i>norvegicus</i>.</p

Quantitative Proteome Analysis of <i>Leishmania donovani</i> under Spermidine Starvation

<div><p>We have earlier reported antileishmanial activity of hypericin by spermidine starvation. In the current report, we have used label free proteome quantitation approach to identify differentially modulated proteins after hypericin treatment. A total of 141 proteins were found to be differentially regulated with ANOVA P value less than 0.05 in hypericin treated <i>Leishmania</i> promastigotes. Differentially modulated proteins have been broadly classified under nine major categories. Increase in ribosomal protein S7 protein suggests the repression of translation. Inhibition of proteins related to ubiquitin proteasome system, RNA binding protein and translation initiation factor also suggests altered translation. We have also observed increased expression of Hsp 90, Hsp 83–1 and stress inducible protein 1. Significant decreased level of cyclophilin was observed. These stress related protein could be cellular response of the parasite towards hypericin induced cellular stress. Also, defective metabolism, biosynthesis and replication of nucleic acids, flagellar movement and signalling of the parasite were observed as indicated by altered expression of proteins involved in these pathways. The data was analyzed rigorously to get further insight into hypericin induced parasitic death.</p></div

Cladogram showing phylogenetic analysis of different proteins form protein protein interaction network.

<p>The phylogenetic correlation between proteins from protein protein interaction network has been analysed by using Clustal W2. The closely related proteins are clustered together whereas distanly related proteins are placed distantly in the cladogram.</p

Distribution of up regulated proteins after hypericin treatment into major categories.

Any increase above fold 1 indicates up-regulation. The table includes up-regulated proteins with ANOVA value less than 0.05.</p

Bar diagram showing percentage of up-regulated and down-regulated (up-regulated above 1.5 fold and down-regulated below 0.9 fold with ANOVA value less than 0.05) proteins of <i>Leishmania donovani</i> after hypericin treatment based on their functional classification.

<p>Bar diagram showing percentage of up-regulated and down-regulated (up-regulated above 1.5 fold and down-regulated below 0.9 fold with ANOVA value less than 0.05) proteins of <i>Leishmania donovani</i> after hypericin treatment based on their functional classification.</p

Pie chart showing relative distribution of differentially modulated proteins (up regulated above 1.5 fold and down regulated below 0.9 fold with ANOVA value less than 0.05) of <i>Leishmania donovani</i> after hypericin treatment.

<p><b>(A)</b> Pie chart of total proteins being altered after hypericin treatment showing their relative distribution among 9 major categories. <b>(B)</b> Pie chart of up regulated proteins after hypericin treatment showing their relative distribution. <b>(C)</b> Pie chart of down regulated proteins after hypericin treatment showing their relative distribution.</p

Distribution of down-egulated proteins after hypericin treatment into major categories.

<p>Any decrease below fold 1 indicates down-regulation. The table includes down-regulated proteins with ANOVA value less than 0.05.</p

<i>In silico</i> modeling of <b>β</b>-carbonic anhydrase inhibitors from the fungus <i>Malassezia globosa</i> as antidandruff agents

<p>A quantitative structure–activity relationship (QSAR) study of sulfonamide inhibitors targeting the β-carbonic anhydrase (CA, EC 4.2.1.1) from the fungus <i>Malassezia globosa</i> is reported. A large set of PRECLAV descriptors has been used to obtain four parametric models. This study presents QSAR data on a pool of 28 compounds. The quality of prediction is high enough (SE = 0.3446, <i>r</i>² = 0.8687, <i>F</i> = 39.6921, <i>Q</i> = 0.7446). A heuristic algorithm selected the best multiple linear regression (MLR) equation which showed the correlation between the observed values and the calculated values of activity. The proposed prediction set included new, not yet synthesized, 23 molecules having various structures. Many compounds in the prediction set seem to possess higher computed activity compared to the presently available <i>M. globosa</i> β-CA inhibitors.</p