An environmentally benign procedure for the hydrogenation of unprotected indoles is described. The hydrogenation reaction is catalyzed by Pt/C and activated by p-toluenesulfonic acid in water as a solvent. The efficacy of the method is illustrated by the hydrogenation of a variety of substituted indoles to their corresponding indolines which were obtained in excellent yields.

A series of ruthenium polypyridyl complexes are presented incorporating π-extended electron rich derivatives of the 8-oxyquinolate (OQN) ligand. The π-donating property of the OQN ligand introduces covalent character to the Ru(dπ)-OQN(π) bonding scheme enhancing its light harvesting properties and diversifying its redox properties, relative to the classic ruthenium(II) trisbipyridyl complex [Ru(bpy)3](2+). Synthesis and characterization is presented for the complexes [Ru(bpy)2(R-OQN)](PF6), where bpy = 2,2'-bipyridine and R = 5-phenyl, 5,7-diphenyl, 2,4-diphenyl, 5,7-bis(4-methoxyphenyl), 5,7-bis(4-(diphenylamino)phenyl). A comprehensive bonding analysis is presented for the [Ru(bpy)2(OQN)](+) system illustrating the origin of its unique spectroscopic and redox properties relative to [Ru(bpy)3](2+). This model is then extended to enable a consistent interpretation of spectra and redox properties for the π-extended [Ru(bpy)2(R-OQN)](PF6) series. Electronic structures have been probed experimentally by a combination of electrochemical and spectroscopic techniques (UV-vis-NIR absorption, emission, EPR spectroscopy) where (metal-ligand)-to-ligand (MLLCT) charge-transfer properties are described by time dependent-density functional theory (TD-DFT) analysis, at the B3LYP/6-31g(d,p) level of approximation. Substantial mixing, due to bonding and antibonding combinations of Ru(dπ) and OQN(π) orbitals, is observed at the HOMO and HOMO-3 levels for the ruthenium-oxyanion bond in [Ru(bpy)2(OQN)](+), which is responsible for the low-energy MLLCT based electronic transition and destabilization of the HOMO level viz. cyclic voltammetry. This noninnocent π-bonding phenomenon is consistent throughout the series which allows for controlled tuning of complex redox potentials while maintaining panchromatic absorption properties across the visible spectrum. Extensive charge delocalization is observed for the one-electron oxidized species using a combination of UV-vis-NIR, EPR spectroelectrochemistry, and Mulliken spin-density analysis, giving strong evidence for hole-delocalization across the delocalized Ru(dπ)-OQN(π) system, in particular for the electron rich 5,7-bis(4-methoxyphenyl) and 5,7-bis(4-(diphenylamino)phenyl) systems.

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A broad group of structurally diverse small organofluorine inhibitors have been synthesized and evaluated in the self-assembly of amyloid β. The major goal was to generate a diverse library of compounds with the same functional group and observe general structural features that characterize the oligomer and fibril inhibitors, and ultimately find lead structures for further, focused inhibitor design. The common structural motifs in these compounds were the CF3-C-OH or CF3-C-NH groups that were proposed to be a binding unit in our earlier studies. A broad range of potential small molecule inhibitors were synthesized by adding different carbocyclic and heteroaromatic rings with an array of substituents, overall 106 molecules. The compounds were tested by standard methods, such as thioflavine T-fluorescence spectroscopy for following fibril formation, biotinyl-Aβ(1–42) single-site streptavidin-based assay for observing oligomer formation and atomic force microscopy for morphological studies. These assays yielded a number of structures that showed significant inhibition against either fibril or oligomer formation. A detailed analysis on the structure activity relationship of anti-fibril and -oligomer properties is provided. In addition, these data present further experimental evidence for the distinct nature of the fibril vs oligomer formation and that the interaction of the Aβ peptide with chiral small molecules is not stereospecific in nature.

A series of compounds containing an α,β-unsaturated carbonyl moiety, such as chalcones and coumarins were designed, synthesized and tested in a variety of assays to assess their potential as anti-Alzheimers’ disease (AD) agents. The investigations included the inhibition of cholinesterases (AChE, BuChE), the inhibition of amyloid beta (Aβ) self-assembly and the disassembly of preformed Aβ oligomers. Several compounds showed excellent inhibition in multiple assays and thus are potential multifunctional compounds for AD. Docking studies for 16 that performed well in all the assays gave a clear interpretation of various interactions in the gorge of AChE. Based on the results, the long-chain coumarin scaffold appears to be a promising structural template for further AD drug development.