A bimetallic terbium(III)/copper(II) complex (Tb-1·Cu2+) for the time-gated luminescent detection of hydrogen sulfide in aqueous samples is reported. The probe shows excellent selectivity towards HS− over various anions and cations, including the ions common to natural waterways and waste water samples, displaying a 73-fold increase in luminescence in the presence of sulfide. The probe exhibits extremely fast reaction times and a low limit of detection (130 nM). The probe was used to quantify sulfide in an industrial “sour water” sample, with the result in excellent agreement with those from two independent assay methods (methylene blue and AzMC).

Two new bifunctional macrocyclic chelate ligands that form luminescent terbium(III) complexes featuring an alkyne group for conjugation to (bio)molecules via the Cu(I)-catalyzed “click” reaction were synthesized. Upon ligation, the complexes exhibit a significant luminescent enhancement when excited at the λmax of the “clicked” products. To demonstrate the utility of the complexes for luminescent labeling, they were conjugated in vitro to E. coli aspartate/glutamate-binding protein incorporating a genetically encoded p-azido-l-phenylalanine or p-(azidomethyl)-l-phenylalanine residue. The complexes may prove useful for time-gated assay applications.

Several rationally designed pyrimidine-based scaffolds intended to mimic the spatial projection of the i, i+3, and i+7 residues of an α-helix and also possess improved aqueous solubility were prepared. A Biginelli-oxidation process was used to form the central pyrimidine ring of these scaffolds, which was subsequently manipulated to form pyrimidine-based tercyclic α-helix mimetics. A pyrimidine-based scaffold designed to mimic the α-helical BH3 domain of the pro-apoptotic Bak protein was also prepared as a putative inhibitor of the Bcl-xL/Bak protein-protein interaction. The pyrimidine-based tercyclic α-helix mimetics, and the putative Bcl-xL inhibitor, were assessed using a luminescence competition assay, however, none displayed inhibitory activity against Bcl-xL or Mcl-1.

•Lanthanide–azide based sulfide sensors were synthesized and characterized.•The probes have excitation and emission profiles compatible with sulfide-contaminated samples from the petrochemical industry.•A terbium-based probe was used to measure the sulfide concentration in oil refinery wastewater.•A europium-based probe had compatibility with partially refined crude oil samples.A series of lanthanide-based, azide-appended complexes were investigated as hydrogen sulfide-sensitive probes. Europium complex 1 and Tb complex 3 both displayed a sulfide-dependent increase in luminescence, while Tb complex 2 displayed a decrease in luminescence upon exposure to NaHS. The utility of the complexes for monitoring sulfide levels in industrial oil and water samples was investigated. Complex 3 provided a sensitive measure of sulfide levels in petrochemical water samples (detection limit ∼ 250 nM), while complex 1 was capable of monitoring μM levels of sulfide in partially refined crude oil.

Tercyclic scaffolds, designed to have improved synthetic accessibility and aqueous solubility, were evaluated as structural α-helix mimetics by using an iterative in silico approach. The synthesis of these tercyclic scaffolds was accomplished using a modular synthetic approach by employing functionalised methoxyphenyl units which were readily manipulated to allow the introduction of various nitrogen-based heterocycles. The ability of these scaffolds to mimic the key i, i + 3 and i + 7 residues of a polyalanine α-helix was ratified by in silico studies, X-ray crystallographic and NOESY analysis, and their aqueous solubility was measured by a kinetic turbidimetric method.

The first enantioselective total syntheses of the proposed structures of the natural product prevezol B are reported. The reported syntheses complement the previously-reported syntheses of the proposed structures of prevezol C, a stereoisomer of prevezol B. It was previously shown that the structure of the naturally occurring prevezol C had been incorrectly assigned. This work has led us to conclude that the proposed structures of prevezol B are also incorrect and major revision of both of the structures of the prevezols B and C is required. Cytotoxicity studies on the human cervical cancer cell line HeLa revealed that the synthesized prevezol B and C compounds were not active even at the highest concentration used (100 μM). However, one of the synthetic precursors was shown to have modest potency against HeLa cells (IC50 = 23.5 ± 1.8 μM).

The first enantioselective synthesis of the proposed relative structures of Prevezol C is reported in 11 linear steps from readily available materials. The unusual syn bromohydrin was installed via a multistep sequence culminating in a diastereoselective geminal dibromide reduction. Discrepancies in the spectral data of the synthetic materials and the natural sample have led to the conclusion that the proposed structures are incorrect.

(−)-2-epi-Prevezol C was readily accessed from the chirons (−)- and (+)-limonene oxide in a total of nine steps and in 24% yield. This efficient enantioselective synthesis of this complex product utilises a highly stereoconvergent, substrate-controlled allylic alkylation strategy to assemble rapidly the unprecedented diterpene core.(−)-2-epi-Prevezol C was readily accessed from the chirons (−)- and (+)-limonene oxide in a total of nine steps and in 24% yield.

Tercyclic scaffolds, designed to have improved synthetic accessibility and aqueous solubility, were evaluated as structural α-helix mimetics by using an iterative in silico approach. The synthesis of these tercyclic scaffolds was accomplished using a modular synthetic approach by employing functionalised methoxyphenyl units which were readily manipulated to allow the introduction of various nitrogen-based heterocycles. The ability of these scaffolds to mimic the key i, i + 3 and i + 7 residues of a polyalanine α-helix was ratified by in silico studies, X-ray crystallographic and NOESY analysis, and their aqueous solubility was measured by a kinetic turbidimetric method.

The first enantioselective total syntheses of the proposed structures of the natural product prevezol B are reported. The reported syntheses complement the previously-reported syntheses of the proposed structures of prevezol C, a stereoisomer of prevezol B. It was previously shown that the structure of the naturally occurring prevezol C had been incorrectly assigned. This work has led us to conclude that the proposed structures of prevezol B are also incorrect and major revision of both of the structures of the prevezols B and C is required. Cytotoxicity studies on the human cervical cancer cell line HeLa revealed that the synthesized prevezol B and C compounds were not active even at the highest concentration used (100 μM). However, one of the synthetic precursors was shown to have modest potency against HeLa cells (IC50 = 23.5 ± 1.8 μM).

A bimetallic terbium(III)/copper(II) complex (Tb-1·Cu2+) for the time-gated luminescent detection of hydrogen sulfide in aqueous samples is reported. The probe shows excellent selectivity towards HS− over various anions and cations, including the ions common to natural waterways and waste water samples, displaying a 73-fold increase in luminescence in the presence of sulfide. The probe exhibits extremely fast reaction times and a low limit of detection (130 nM). The probe was used to quantify sulfide in an industrial “sour water” sample, with the result in excellent agreement with those from two independent assay methods (methylene blue and AzMC).