Synthesis and photochemistry of a new class of photocleavable protein cross-linking reagents

A new series of photocleavable protein cross-linking reagents based on bis(maleimide) derivatives of diaryl disulfides have been synthesised. They have been functionalised with cysteine and transient absorption spectra for the photolysis reaction have been recorded by using the pump-probe technique with a time resolution of 100 femtoseconds. Photolysis of the disulfide bond yields the corresponding thiyl radicals in less than a picosecond. There is a significant amount of geminate recombination, but some of the radicals escape the solvent cage and the quantum yield for photocleavage is 30 % in water.     

Enantio- and diastereodifferentiating cis,trans-photoisomerization of 2beta,3beta-diphenylcyclopropane-1alpha-carboxylic acid derivatives in organized media

[reaction: see text] Four methods of asymmetric induction in the cis, trans-photoisomerization of 2beta, 3beta-diphenylcyclopropane-1alpha-carboxylic acid derivatives were studied. Best results (ca. 80% de) were obtained by irradiation of chiral esters, amides, and salts in NaY and LiY zeolites and in the pure crystalline state.     

Templating and selection in the formation of macrocycles containing [[P(micro-NtBu)(2)](micro-NH)](n) frameworks: observation of halide ion coordination

Amination of [ClP(micro-NtBu)](2) (1) using NH(3) in THF gives the cyclophospha(III)zane dimer [H(2)NP(micro-NtBu)](2) (2), in good yield. (31)P NMR spectroscopic studies of the reaction of 1 with 2 in THF/Et(3)N show that almost quantitative formation of the cyclic tetramer [[P(micro-NtBu)](2)(micro-NH)](4) (3) occurs. The remarkable selectivity of this reaction can (in part) be attributed to pre-organisation of 1 and 2, which prefer cis arrangements in the solid state and solution. The macrocycle 3 can be isolated in yields of 58-67 % using various reaction scales. The isolation of the major by-product of the reaction (ca. 0.5-1 % of samples of 3), the pentameric, host-guest complex [[P(micro-NtBu)(2)](2)(micro-NH)](5)(HCl).2 THF] (4.2 THF), gives a strong indication of the mechanism involved. In situ (31)P NMR spectroscopic studies support a stepwise condensation mechanism in which Cl(-) ions play an important role in templating and selection of 3 and 4. Amplification of the pentameric arrangement occurs in the presence of excess LiX (X=Cl, Br, I). In addition, the cyclisation reaction is solvent- and anion-dependent. The X-ray structures of 2 and 4.2 THF are reported.     

Effect of hydrodynamic interactions on the evolution of chemically reactive ternary mixtures

We investigate the structural evolution of an A/B/C ternary mixture in which the A and B components can undergo a reversible chemical reaction to form C. We developed a lattice Boltzmann model for this ternary mixture that allows us to capture both the reaction kinetics and the hydrodynamic interactions within the system. We use this model to study a specific reactive mixture in which C acts as a surfactant, i.e., the formation of C at the A/B interface decreases the interfacial tension between the A and B domains. We found that the dynamics of the system is different for fluids in the diffusive and viscous regimes. In the diffusive regime, the formation of a layer of C at the interface leads to a freezing of the structural evolution in the fluid; the values of the reaction rate constants determine the characteristic domain size in the system. In the viscous regime, where hydrodynamic interactions are important, interfacial reactions cause a slowing down of the domain growth, but do not arrest the evolution of the mixture. The results provide guidelines for controlling the morphology of this complex ternary fluid.     

Self-assembly of tetrahedral and trigonal antiprismatic clusters [Fe4(L4)4] and [Fe6(L5)6] on the basis of trigonal tris-bidentate chelators

In a one-pot reaction, the tetranuclear iron chelate complex [Fe4(L4)4] 6 was generated from benzene-1,3,5-tricarboxylic acid trichloride (4), bis-tert-butyl malonate (5a), methyllithium, and iron(II) dichloride under aerobic conditions. Alternatively, hexanuclear iron chelate complex [Fe(L5)6] 7 was formed starting from bis-para-tolyl malonate (5b) by employing identical reaction conditions to those applied for the synthesis of 6. The clusters 6 and 7 are present as racemic mixtures of homoconfigurational (delta,delta,delta,delta)/(lambda,lambda,lambda,lambda)-fac or (delta,delta,delta,delta,delta,delta)/(lambda,lambda,lambda,lambda,lambda,lambda)-fac stereoisomers. The structures of 6 and 7 were unequivocally resolved by single-crystal X-ray analyses. The all-iron(III) character of 6 and 7 was determined by M?ssbauer spectroscopy.     

Synthesis of 2-aryl-6-methyl-5-nitroquinoline derivatives as potential prodrug systems for reductive activation

A range of novel 2-aryl-5-nitroquinolines have been synthesised as potential prodrug systems for bioreductive activation. Thus 5-nitroquinoline underwent vicarious nucleophilic substitution at C-6 with bromoform anion to give, after hydrolysis and reduction, the quinoline-6-methanol. Introduction of chlorine at C-2 was followed by palladium-catalysed Suzuki coupling to install the 2-aryl substituent. A fluorescent model ‘drug’, 7-hydroxy-4-methylcoumarin was coupled to the 6-hydroxymethyl group, and its fragmentation upon reduction of the nitro group was investigated.     

Stereoselective Palladium‐Catalyzed C−F Bond Alkynylation of Tetrasubstituted gem‐Difluoroalkenes

A stereoselective Pd(PPh₃)₄‐catalyzed C?F bond alkynylation of tetrasubstituted gem‐difluoroalkenes with terminal alkynes has been developed. This method gives access to a great variety of conjugated monofluoroenynes bearing a tetrasubstituted alkene moiety with well‐defined stereochemistry. Chelation‐assisted oxidative addition of Pd to the C?F bond is proposed to account for the high level of stereocontrol. An X‐ray crystal structure of a key monofluorovinyl Pd^II intermediate has been obtained for the first time as evidence for the proposed mechanism.