Covalent and non-covalent albumin binding of Au(i) bis-NHCs via post-synthetic amide modification

Recent decades have witnessed the emergence of Au(i) bis-N-heterocyclic carbenes (NHCs) as potential anticancer agents. However, these systems exhibit little interaction with serum proteins (e.g., human serum albumin), which presumably impacts their pharmacokinetic profile and tumor exposure. Anticancer drugs bound to human serum albumin (HSA) often benefit from significant advantages, including longer circulatory half-lives, tumor targeted delivery, and easier administration relative to the drug alone. In this work, we present Au(i) bis-NHCs complexes, 7 and 9, capable of binding to HSA. Complex 7 contains a reactive maleimide moiety for covalent protein conjugation, whereas its congener 9 contains a naphthalimide fluorophore for non-covalent binding. A similar drug motif was used in both cases. Complexes 7 and 9 were prepared from a carboxylic acid functionalized Au(i) bis-NHC (complex 2) using a newly developed post-synthetic amide functionalization protocol that allows coupling to both aliphatic and aromatic amines. Analytical, and in vitro techniques were used to confirm protein binding, as well as cellular uptake and antiproliferative activity in A549 human lung cancer cells. The present findings highlight a hitherto unexplored approach to modifying Au(i) bis-NHC drug candidates for protein ligation and serve to showcase the relative benefits of covalent and non-covalent HSA binding.

Au(i) bis-N-heterocyclic carbenes (NHCs) functionalized using an amide linker were found to bind to human serum albumin (HSA) in covalent and non-covalent fashion. The solubility and in vitro anti-cancer activity of these new conjugates were studied.     

Phase diagram study of CaBr2–CaHBr system

A study of binary, CaBr₂–CaHBr system was carried out by differential thermal analysis (DTA), covering the composition range from 100 % CaBr₂ to 100 % CaHBr between room temperature and 800 °C. From DTA results, the contour of solidus and liquidus temperatures with composition is plotted and the phase diagram of CaBr₂–CaHBr system is constructed. The system shows an eutectic reaction at 576 °C and the eutectic composition is 79.6 mol% CaBr₂. Co-existing phases in different phase fields are characterized by X-ray diffraction analysis.     

ZrOCl2•8H2O-Catalyzed One-Pot Multicomponent Synthesis of β′-Acetamido-β-dicarbonyl Compounds with Special Reference to pref-Selective β′-Acetamido-β-ketoesters

ZrOCl₂ · 8H₂O catalyzes the one-pot synthesis of β′-acetamido-β-dicarbonyl compounds in high yields from aldehyde, enolizable β-dicarbonyl compound, acetyl chloride, and acetonitrile in solvent as well as in solvent-free conditions. β′-Acetamido-β-ketoesters are formed in moderate to exclusive pref-diastereoselectivity.     

Phase diagram study of CaBr2–LiBr system using DTA

The phase diagram of binary LiBr–CaBr₂ system was investigated using differential thermal analysis (DTA) between room temperature and 800 °C. From the DTA results obtained over the entire range of composition from pure LiBr to pure CaBr₂ in steps of ~5 mol%, the phase diagram was constructed and is reported here. The results indicated the possible existence of a compound at 50 mol% LiBr, namely, LiCaBr₃. The compound undergoes peritectic decomposition at 552 °C. The system shows a eutectic reaction at 532 °C between this compound and LiBr phase, and the eutectic composition is close to 80 mol% LiBr. The compound LiCaBr₃ decomposes into CaBr₂ and LiBr phases below 272 °C. Co-existing phases in different phase fields are characterized by X-ray diffraction analysis.     

β-Hydroxy-α-tosyloxy esters as chiral building blocks for the enantioselective synthesis of benzo-annulated oxa-heterocycles: scope and limitations

The enantioselective synthesis of benzo-annulated oxa-heterocycles 2,3-dihydrobenzofuran and 1-benzopyran derivatives is described using β-hydroxy-α-tosyloxy esters as chiral building blocks, which are easily accessible through the regioselective α-tosylation of Sharpless asymmetric dihydroxylation-derived syn-2,3-dihydroxy esters.     

Catechol violet as new, efficient, and versatile ligand for Cu(I)-catalyzed C-S coupling reactions

Combination of CuI and Catechol violet (CuI-CV) was employed as catalyst for the first time in the C-S coupling reaction of a wide variety of aromatic halides, such as aryl iodides, bromo pyridines, activated aryl chlorides, and vinyl iodide with thiols to afford the corresponding thioethers in good to excellent yields. Broad range of functional group tolerance present in both the coupling partners has been observed in this reaction protocol.     

Analysis of fiber optic SPR sensor utilizing platinum based nanocomposites

SPR based fiber optic sensor using nanocomposite is presented. Nanocomposites comprising of Pt nanoparticles with various volume fractions embedded in dielectric matrices of TiO₂ and SnO₂ are considered. Sensitivity enhances with increase in thickness of nanocomposite and volume fraction of nanoparticles for both nanocomposites. Optimized thicknesses are obtained to be 40 and 50 nm for Pt–TiO₂ and Pt–SnO₂ nanocomposites respectively while optimized volume fraction is found to be 0.85 for both nanocomposites. 40 nm thick Pt–TiO₂ nanocomposite based sensor with 0.85 volume fraction possesses utmost sensitivity.     

A small molecule two-photon probe for hydrogen sulfide in live tissues

We report a two-photon probe (FS1) which shows a 21-fold two-photon excited fluorescence enhancement in response to H(2)S and can selectively detect H(2)S in a rat hippocampal slice at a depth of 90-190 μm by using two-photon microscopy.