Synthesis of nitrogen and sulfur macrocycles with cis exogenous oxygen and sulfur donor atoms

A series of new N4 and N8 macrocycles has been prepared, that includes cis-exogenous O2, S2 and S/O atoms to allow chelation to a metal external to the macrocyclic ring. We found that thioamide units within the macrocycles were unstable to attack by secondary amines and thus alkylated precursors containing only tertiary amines could lead to exogenous-S2 macrocycles. Cyclisation of alkylated tetraamine precursors with dimethyloxalate or dithiooxamide led to both N4 and N8 macrocycles via 1 + 1 and 2 + 2 cyclisation reactions with exogenous-O2 or S2 respectively. Alkylation of preformed exogenous-O2 macrocycles was explored and led to alkyl substitution at the secondary amine nitrogens in the ring, however synthesis of these species was overall lower yielding than cyclisation using alkylated tetraamine precursors. Thionation of an exo-O2 macrocycle using an analogue of Lawesson's Reagent led to formation of the analogous exogenous-S2 and exogenous-O,S macrocycles. Related S2N2 macrocycles with exogenous-O2 were prepared by a cyclisation route but could not be isolated free of larger ring analogues.     

Methodological factors influencing measurement and processing of plasma reelin in humans

Background

Reelin, intensively studied as an extracellular protein that regulates brain development, is also expressed in a variety of tissues and a circulating pool of reelin exists in adult mammals. Here we describe the methodological and biological foundation for carrying out and interpreting clinical studies of plasma reelin.

Results

Reelin in human plasma was sensitive to proteolysis, freeze-thawing and heating during long-term storage, sample preparation and electrophoresis. Reelin in plasma was a dimer under denaturing conditions. Boiling of samples resulted in laddering, suggesting that each of the 8 repeats expressed in reelin contains a heat-labile covalent bond susceptible to breakage. Urinary-type and tissue-type plasminogen activator converted reelin to a discrete 310 kDa fragment co-migrating with the major immunoreactive reelin fragment seen in plasma and also detected in brain. (In contrast, plasmin produced a spectrum of smaller unstable reelin fragments.) We examined archival plasma of 10 pairs of age-matched male individuals differing in repeat length of a CGG repeat polymorphism of the 5'-untranslated region of the reelin gene (both alleles < 11 repeats vs. one allele having >11 repeats). Reelin 310 kDa band content was lower in subjects having the long repeats in all 10 pairs, by 25% on average (p < 0.001). In contrast, no difference was noted for amyloid precursor protein.

Conclusions

Our studies indicate the need for caution in measuring reelin in archival blood samples, and suggest that assays of plasma reelin should take into account three dimensions that might vary independently: a) the total amount of reelin protein; b) the relative amounts of reelin vs. its proteolytic processing products; and c) the aggregation state of the native protein. Reelin-plasminogen activator interactions may affect their roles in synaptic plasticity. Our results also suggest that the human CGG repeat polymorphism affects reelin gene expression, and may affect susceptibility to human disease.

     

ReF7 and ReOF5 as fluoride ion donors

Salts containing the ReF₆⁺ ion have been prepared by one-electron oxidation of ReF₆ using KrF⁺ salts. The compounds ReF₆⁺MF₆^? (M = Au, Sb) are of moderate stability, tending to decompose to ReF₇ and the corresponding pentafluoride. This gives rise to isolated ReF₇ and MF₅ molecules within the ionic lattice, whose presence is demonstrated by Raman spectroscopy. Interaction of ReF₆ and PtF₆ produced not the salt ReF₆⁺PtF₆^? (1), but rather the deep red (PtF₅)₄ when PtF₆ was present in excess, and PtF₄ when ReF₆ was in excess. ReF₆ and IrF₆ appear to be in equilibrium with ReF₇ and (IrF₅)₄, possibly via an ionic intermediate ReF₆⁺(IrF₆·xIrF₅)^?.The salts ReOF₄⁺MF_6? (M = As, Au, Sb) have been characterized. In contrast to the behaviour of IOF₅ and IF₇, ReOF₅ is a better fluoride ion donor than ReF₇.     

Coordination chemistry umpolung: a gallane ligand on a phosphine lewis acceptor.

Pentaphenylphosphinophosphonium trifluoromethanesulfonate reacts with amino-iminogall(I)ane to effect quantitative substitution of Ph3P and formation of the first complex of a gallium Lewis base on a phosphine Lewis acid.     

Phosphorus-nitrogen-phosphorus ligands: cooperative effects between nitrogen and phosphorus substituents on catalytic activity

A new generation of PNP compounds bearing different diarylphosphine groups were prepared and used as ligands in palladium-catalysed Suzuki cross-coupling reactions. Rates of oxidative addition of iodobenzene to (PNP)Pd[0] complexes were measured using UV spectroscopy. Synergistic effects between the N- and P- substituents were identified and correlated in redox and catalytic chemistry.     

MONOADDITION OF DICTAMNINE TO SYNTHETIC DOUBLE-STRANDED POLYDEOXYRIBONUCLEOTIDES IN UVA AND THE EFFECT OF PHOTOMODIFIED DNA ON TEMPLATE ACTIVITY

Abstract— The photoreactivity of dictamnine, a furoquinoline alkaloid, towards different synthetic DNAs has been studied. The ratio of the photobinding of [₃H]-dictamnine to poly(dA-dT) poly(dA-dT): poly(dG-dC) poly(dG-dC): poly(dA-dU) poly(dA-dU): poly(dA) poly(dT), in relation to that of calf thymus DNA, is 18:1:0.5:0.3. Prior treatment of calf thymus DNA with dictamnine in light inhibits the subsequent incorporation of 8-methoxypsoralen (8-MOP). These results suggest that the sites in DNA for the photobinding of dictamnine are probably identical with those for monoad-ducts of 8-MOP. Furthermore, the template activity of photomodified DNA in the RNA polymerase reaction is considerably inhibited for poly(dA-dT)poly(dA-dT), to a lesser extent for calf thymus DNA, but almost not affected for the linear copolymer, poly(dA)-poly(dT).     

A unique new multiband molecular conductor: [BDTA][Ni(dmit)2]2

A new molecular conducting material, [BDTA][Ni(dmit)2]2, with a novel multiband electronic structure has been prepared by simple mixing of precursor salts of the components.     

Monte Carlo simulation of segregation in ceramic thin films

A Monte Carlo exchange technique is used to study segregation in thin ceramic films with application to MgO/MnO. The approach is not restricted to the dilute limit. Surface concentrations as a function of temperature and film composition are determined directly from the simulations. For all compositions studied (Mn(chi)Mg(1-chi)O, 0 < or = chi < or = 1) the (001) surface is Mn(2+) rich; the occupancy of sites by Mn(2+) decreases rapidly with depth. The ratio of the number of Mn(2+) to Mg(2+) ions at the surface decreases as a function of temperature. The calculated enthalpies of segregation of Mn(2+) for the thin film are strongly dependent on the total Mn(2+) concentration at small Mn(2+) concentrations, with the enthalpy of segregation varying by a factor of two with surface coverage.     

Structural studies of {Li} 2-lithiopyrrolidines using NMR spectroscopy

A selection of N-substituted 2-lithiopyrrolidines were prepared and their structures were investigated by ⁶Li and ¹³C NMR spectroscopy. Evidence is presented for aggregation and dynamic solvation effects, depending on the nature of the N-substituent and substituents on the pyrrolidine ring. Studies were performed with N-Boc (coordinating carbonyl group), N-methoxyethyl (coordinating methoxy group) and N-alkyl (no coordinating group) heterocycles to represent three different classes of organolithiums: dipole-stabilized, unstabilized and chelated, and unstabilized.     

A binaphthyl-containing Eu(III) complex and its interaction with human serum albumin: a luminescence study

On binding to human serum albumin (HSA), the Eu(III) luminescent emission enhancement of a complex containing a binaphthyl chromophore enables the determination of binding constants, showing no chiral discrimination for the (R)- (K= 8200 +/- 810 M(-1)) and (S)-enantiomers (K= 7710 +/- 460 M(-1)).