A one-step route to azomethine ylides via chloroiminium salts

A new, one-step procedure for the generation of azomethine ylides, 4 and 20, via chloroiminium salts, 3 and 19, is reported. The generation of the azomethine ylides was confirmed by their trapping with dimethyl acetylenedicarboxylate (DMAD) which, upon spontaneous 1,4-dehydrochlorination, gave the corresponding pyrroles 17 and 21.     

The synthesis,structural characterization and biological evaluation of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives as potential anticancer agents

A series of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i and 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i have been synthesized by coupling ferrocenylmethyl amine 3 with various substituted N‐(fluorobenzoyl) amino acid derivatives using the standard N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride, 1‐hydroxybenzotriazole protocol. The amino acids employed in this study were glycine and L‐alanine. All of the compounds were fully characterized using a combination of ¹H NMR, ¹³C NMR, ¹⁹F NMR, distortionless enhancement by polarization transfer (DEPT)‐135, ¹H–¹H correlation spectroscopy (COSY) and ¹H–¹³C COSY (heteronuclear multiple‐quantum correlation) spectroscopy. The compounds were biologically evaluated on the oestrogen‐positive MCF‐7 breast cancer cell line. Compounds 4g , 4i , 5h and 5i exhibited cytotoxic effects on the MCF‐7 breast cancer cell line. N‐(Ferrocenylmethyl‐L‐alanine)‐3,4,5‐trifluorobenzene‐carboxamide ( 5h ) was the most active compound, with an IC₅₀ value of 2.84 μm . Compounds 4i , 5h and 5i had lower IC₅₀ values than that found for the clinically employed anticancer drug cisplatin (IC₅₀ = 16.3 μm against MCF‐7). Guanine oxidation studies confirmed that 5h was capable of generating oxidative damage via a reactive oxygen species‐mediated mechanism. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and testing of chromogenic phenoxazinone substrates for beta-alanyl aminopeptidase

Novel 7-N-(beta-alanyl)aminophenoxazin-3-one salts 27a-d have been synthesized and tested as chromogenic substrates for beta-alanyl aminopeptidase, which is present in Pseudomonas aeruginosa, the most common respiratory pathogen in patients with cystic fibrosis. The biological results show that 7-N-(beta-alanyl)amino-1-pentylphenoxazin-3-one trifluoroacetate salt 27a is a chromogenic substrate for this bacterium, with a low degree of diffusion in nutrient media for growing bacterial cultures and a bright red colour, making it easily distinguishable from the agar background.     

Negative Temperature Sensitive Hydrogels in Controlled Drug Delivery

Summary: PVP/PNIPAAm copolymers exhibit a temperature sensitive nature that makes them an attractive candidate for controlled drug delivery devices. Diclofenac sodium was added to the monomeric mixture, which included an initiator and crosslinking agent (where appropriate), prior to UV photopolymerisation. It was found that the xerogels retained similar properties as the original samples (not containing drug) at lower levels of drug integration. In all cases, drug dissolution analysis showed that the active agent was released at a slower rate at temperatures above the Lower Critical Solution Temperature (LCST). Interestingly, the drug release trends were almost identical for both the physically and chemically crosslinked hydrogels, when the decrease in transition temperature caused by the incorporated crosslinking agent is taken into consideration. It is believed that both types of copolymers reached a constant maximum swollen weight at a set of temperatures above their transition temperatures. When this swollen plateau is attained, the hydrophilic-hydrophobic interactions are balanced, thus the gel does not swell or shrink further and the drug diffuses out at a constant rate.     

Synthesis and evaluation of halogenated nitrophenoxazinones as nitroreductase substrates for the detection of pathogenic bacteria

The synthesis and microbiological evaluation of 7-, 8- and 9-nitro-1,2,4-trihalogenophenoxazin-3-one substrates with potential in the detection of nitroreductase-expressing pathogenic microorganisms are described. The 7- and 9-nitrotrihalogenophenoxazinone substrates were reduced by most Gram-negative microorganisms and were inhibitory to the growth of certain Gram-positive bacteria; however, the majority of Gram-positive strains that were not inhibited by these agents, along with the two yeast strains evaluated, did not reduce the substrates. These observations suggest there are differences in the active site structures and substrate requirements of the nitroreductase enzymes from different strains; such differences may be exploited in the future for differentiation between pathogenic microorganisms. The absence of reduction of the 8-nitrotrihalogenophenoxazinone substrates is rationalized according to their electronic properties and correlates well with previous findings.     

Ligand functionalization as a deactivation pathway in a fac-Ir(ppy)3-mediated radical addition

Knowledge of the kinetic behavior of catalysts under synthetically relevant conditions is vital for the efficient use of compounds that mediate important transformations regardless of their composition or driving force. In particular, these data are of great importance to add perspective to the growing number of applications of photoactive transition metal complexes. Here we present kinetic, synthetic, and spectroscopic evidence of the mechanistic behavior of fac-Ir(ppy)₃ in a visible light-mediated radical addition to 3-methylindole, demonstrating the instability of fac-Ir(ppy)₃ under these conditions. During the reaction, rapid in situ functionalization of the photocatalyst occurs, eventually leading to deactivation. These findings demonstrate a conceivable deactivation process for catalytic single electron reactions in the presence of radicophilic ligands. Attempts to inhibit photocatalyst deactivation through structural modification provide further insight into catalyst selection for a given system of interest.     

Synthesis and evaluation of fluorogenic 2-amino-1,8-naphthyridine derivatives for the detection of bacteria

Several novel fluorogenic N-aminoacylnaphthyridine substrates were synthesized in good yield and tested for their ability to detect pathogenic bacteria in agar-based cell culture. Simple 2-N-(β-alanyl)amino-5,7-dialkylnaphthyridine substrates were selectively hydrolysed by β-alanylaminopeptidase expressing bacteria, but were subject to diffusion in the agar medium. Diffusion was reduced in the 2-N-(β-alanyl)amino-7-alkylnaphthyridine substrates with longer alkyl chains, but inhibition of growth was increased. 2-N-(β-Alanyl)amino-7-octylnaphthyridine inhibited the growth of all species tested, except for strains resistant to colistin/polymyxin, providing a rationale for the development of substrates for the selective detection of drug resistant species in clinical samples.     

A relative rate study of the reaction of chlorine atoms (Cl) and hydroxyl radicals (OH) with a series of ethers

Rate constants for the gas phase reactions of hydroxyl radicals and chlorine atoms with a number of ethers have been determined at 300 ± 3 K and at a total pressure of 1 atmosphere. Both OH radical and chlorine atom rate constants were determined using a relative rate technique. Values for the rate constants obtained are as follows.