Steven J. Black

Adenophostin A and analogues modified at the adenine moiety: synthesis, conformational analysis and biological activity

The synthesis of adenophostin A (2) and two analogues [etheno adenophostin (4) and 8-bromo adenophostin (5)] modified at the adenine moiety, is reported. A combination of NMR analysis and molecular modelling was used to compare their structures in solution and determined that they all adopt very similar conformations. The analogues were tested for their ability to mobilise Ca(2+) from DT40 cells expressing recombinant Type 1 rat Ins(1,4,5)P(3)R which reveals etheno adenophostin as a high affinity fluorescent probe of the Ins(1,4,5)P(3)R. 8-Bromo adenophostin was only slightly less potent. The biological results support our current hypothesis regarding the binding mode of adenophostin A at the Ins(1,4,5)P(3)R, i. e. that a cation-pi interaction between the base moiety and Arg 504 of the receptor in combination with H-bonding may be responsible for the high potency of adenophostin A relative to Ins(1,4,5)P(3).

Formation of a remarkably robust 2∶1 complex between β-cyclodextrin and a phenyl-substituted icosahedral carborane

The structure of the 2:1 complex between beta-cyclodextrin and 1-phenyl-1,2-dicarba-closo-dodecaborane(12) is demonstrated by NOE and NOESY spectroscopy; this complex is remarkably refractory.

First enzymatic synthesis of an N1-cyclised cADPR (cyclic-ADP ribose) analogue with a hypoxanthine partial structure: discovery of a membrane permeant cADPR agonist

Nicotinamide 8-Br-hypoxanthine dinucleotide (8-Br-NHD+) was cyclised at the N1 position by the ADP-ribosyl cyclase from Aplysia californica to give cyclic 8-Br-inosine diphosphoribose (8-Br-N1-cIDPR), a novel membrane-permeant agonist of Ca2+ release in human T cells.

SYNTHESIS, CRYSTAL AND MOLECULAR STRUCTURE OF A NOVEL ORGANOANTIMONY CAGE COMPOUND, C4BUT4P4SB2

The reaction of the hetero-ring anion [P 2 SbC 2 Bu t 2 ] - with FeCl 3 affords the organoantimony cage compound, C 4 Bu t 4 P 4 Sb 2 , via a proposed oxidative coupling reaction; the X-ray crystal structure of the cage displays weak intermolecular interactions.

Synthesis and structural characterisation of a novel 2,3-distibene-1,4-dione complex, [Pt(PEt3)2{η2-ButC(O)SbSbC(O)But}]

The reaction of cis-[PtCl2(PEt3)2] with 2 equiv. of [{[Li{η2-OC(But)EC(But)O}(DME)0.5]2}∞], E = Sb or As, affords either the first distibene-dione complex, cis-[Pt(PEt3)2{η2-ButC(O)SbSbC(O)But}], or the related diarsenide-dione bridged complex, trans-[{Pt(PEt3)Cl}2{µ-η1,η1-ButC(O)- AsAsC(O)But}], the X-ray crystal structures of which are described.

THE MOLECULAR STRUCTURE O F [{SbEtBr(μ-Br)[SCN(Me)C2Me2N(Me)]}2]

[Extract] Prior to this work there were no crystallographically characterised examples of imidazolethione adducts of organoantimony compounds and only 3 exaamples of imidazolethione adducts of antimony trihalides [1-3]. The antimony centre in the present compound has a slightly distorted square based pyramidal geometry and a stereochemically active lone pair. The compound sits on an inversion centre and is dimeric thorugh unsymmetrical Sb-Br-Sb bridges, both the longer and shorter interactions of which oie in the normal region for SB-Br bonds [4]. The geometry of the imidazolethione ligand in the complex is similar to its geometry in the uncoordinated state [5].

POLYHETERO-FERROCENES AND -RUTHENOCENES DERIVED FROM THE 1,4,2-DIPHOSPHASTIBOLYL RING ANION P2SBC2BUT2-

The complex [RuCl 2 (PPh 3 ) 3 ] reacted with the 1,4,2-diphosphastibolyl ring anion [P 2 SbC 2 Bu t 2 ] - (containing ca. 25% of the 1,2,4-triphospholyl anion [P 3 C 2 Bu t 2 ] - ) to produce a cocrystallised mixture (crystal structure) of two isomers of [Ru(η 5 -P 2 SbC 2 Bu t 2 ) 2 ] with [Ru(η 5 -P 2 SbC 2 Bu t 2 )(η 5 -P 3 C 2 Bu t 2 )]. Variable-temperature 31 P-{ 1 H} NMR studies on the mixture show one of the isomers and the last complex to be fluxional at room temperature. It is believed that an interring Sb · · · Sb interaction in the other isomer restricts its fluxionality in solution. The reaction of [P 2 SbC 2 Bu t 2 ] - with FeCl 2 yielded only one isomer of the heteroferrocene complex [Fe(η 5 -P 2 SbC 2 Bu t 2 ) 2 ] which is also non-fluxional in solution and has a similar oxidation potential to that of ferrocene itself. The heteroruthenocene complexes [Ru(η 5 -P 2 SbC 2 Bu t 2 )(η 5 -C 5 R 5 )] (R = H or Me) were prepared by treating [Ru(η 5 -C 5 R 5 )(MeCN) 3 ] [PF 6 ] (R = H or Me) with [P 2 SbC 2 Bu t 2 ] - . The analogous ferrocene complex [Fe(η 5 -P 2 SbC 2 Bu t 2 )(η 5 -C 5 Me 5 )] (crystal structure) was synthesized by treating a 1∶1 mixture of [P 2 SbC 2 Bu t 2 ] - and Li(C 5 Me 5 ) with half an equivalent of FeCl 2 . Treatment of [M(η 5 -P 2 SbC 2 Bu t 2 )(η 5 -C 5 Me 5 )] (M = Ru or Fe) with [W(CO) 5 (thf)] (thf = tetrahydrofuran) formed the secondary co-ordination complexes [M(η 5 -P 2 SbC 2 Bu t 2 )(η 5 -C 5 Me 5 ){W(CO) 5 }] (M = Ru or Fe) in which the W(CO) 5 fragment is η 1 ligated to the phosphorus centre adjacent to the ring antimony centre. A diphosphastibolyl-bridged cationic triple-decker complex [(η 5 -C 5 Me 5 )Ru(µ-η 5 : η 5 -P 2 SbC 2 Bu t 2 )Ru(η 5 -C 5 Me 5 )][PF 6 ] was the product of the reaction of [P 2 SbC 2 Bu t 2 ] - with 2 equivalents of [Ru(η 5 -C 5 Me 5 )(MeCN) 3 ] [PF 6 ].