Preparation of phosphinoferrocene carboxamides from isocyanates. Synthesis and structural characterisation of palladium(II) and platinum(II) complexes with 1′-(diphenylphosphino)-1-(N-phenylcarbamoyl)ferrocene

The reaction of in situ generated 1′-(diphenylphosphino)-1-lithioferrocene with isocyanates RNCO affords the respective phosphino-carboxamides Ph₂PfcCONHR (fc = ferrocene-1,1′-diyl, R = cyclohexyl (2), and Ph (3)) in moderate yields. The coordination behaviour of 3 chosen as a representative was studied in palladium(II) and platinum(II) complexes. Depending on the metal precursor and the reaction conditions, the following compounds featuring this ligand as a P-monodentate or an O,P-chelating donor were isolated and characterised by spectroscopic methods (IR, multinuclear NMR and electrospray ionisation MS): trans-[PdCl₂(3-κP)₂] (5), trans-[PtCl₂(3-κP)₂] (6), cis-[PtCl₂(3-κP)₂] (7), [SP-4-4]-[(L^NC)PdCl(3-κP)] (8; L^NC = 2-[(dimethylamino-κN)methyl]phenyl-κC¹), and [SP-4-3]-[(L^NC)PdCl(3-κ²O,P)]SbF₆ (9). Besides, the crystal structures of a phosphine oxide resulting by oxidation of 2, viz Ph₂P(O)fcCONHCy (4), and of complexes 5·2Et₂O and 9 have been determined by single-crystal X-ray diffraction analysis.     

On Manifolds Whose Tangent Bundle is Big and 1-Ample

A line bundle over a complex projective variety is called bigand 1-ample if a large multiple of it is generated by globalsections and a morphism induced by the evaluation of the spanningsections is generically finite and has at most 1-dimensionalfibers. A vector bundle is called big and 1-ample if the relativehyperplane line bundle over its projectivisation is big and1-ample. The main theorem of the present paper asserts that any complexprojective manifold of dimension 4 or more, whose tangent bundleis big and 1-ample, is equal either to a projective space orto a smooth quadric. Since big and 1-ample bundles are ‘almost’ample, the present result is yet another extension of the celebratedMori paper ‘Projective manifolds with ample tangent bundles’(Ann. of Math. 110 (1979) 593–606). The proof of the theorem applies results about contractionsof complex symplectic manifolds and of manifolds whose tangentbundles are numerically effective. In the appendix we re-provethese results. 2000 Mathematics Subject Classification 14E30,14J40, 14J45, 14J50.     

Breakup of 8B and the 7Be(p, γ)8B reaction

The calculated rate of events in some of the existing solar neutrino detectors is directly proportional to the rate of the ⁷Be(p, γ)⁸B reaction measured in the laboratory at low energies. However, the low-energy cross sections of this reaction are quite uncertain as various measurements differ from each other by 30–40%. The Coulomb dissociation process which reverses the radiative capture by the dissociation of ⁸B in the Coulomb field of a target, provides an alternate way of accessing this reaction. While this method has several advantages (like large breakup cross sections and flexibility in the kinematics), the difficulties arise from the possible interference by the nuclear interactions, uncertainties in the contributions of the various multipoles and the higher order effects, which should be considered carefully. We review the progress made so far in the experimental measurements and theoretical analysis of the breakup of ⁸B and discuss the current status of the low-energy cross sections (or the astrophysical S-factor) of the ⁷Be(p, γ)⁸B reaction extracted therefrom. The future directions of the experimental and theoretical investigations are also suggested. Work supported by EPSRC, UK, grant nos J/95867 and L/94574.     

[PtCl3(μ-SCH2C5H9NMe)2PtCl]: First chelate compound of 3-mercaptomethyl-1-methylpiperidine

The title compound, aefh-tetrachloro-cg,db-bis{-[(1-methyl-3-piperidinyl)methanethiolato]--S,N}-diplatinum(II, IV) crystallizes in the monoclinic system, space group P _21/a , with the following crystal data: a = 13.502(2) Å, b = 12.323(2) Å, c = 13.720(3) Å and = 105.92(2)°. It is a dinuclear Pt(II)–Pt(IV) mixed-valence thiolato complex and represents the first chelate compound of 3-mercaptomethyl-1-methyl piperidine. Each ligand is terdentate and simultaneously S,N-chelating and -bridging. The metal environment is approximately square-planar and octahedral for Pt(II) and Pt(IV), respectively, both S₂PtNCl planes generating a dihedral angle of approximately 156°. There is no metal–metal bonding.     

Transmission of trans effects in dinuclear complexes.

The substitution of a terminal hydride ligand in the complexes [Ir(2)(mu-H)(mu-Pz)(2)H(3)(L)P(i)Pr(3))(2)] (L = NCCH(3) (1) or pyrazole (3)) by chloride provokes a significant change in the lability of the L ligand, despite the fact that the substituted hydride and the L ligand lie in opposite extremes of the diiridium(III) complexes. Detailed structural studies of complex 3 and its chloro-trihydride analogue [Ir(2)(mu-H)(mu-Pz)(2)H(2)Cl(HPz)(P(i)Pr(3))(2)] (4) have shown that this behavior is a consequence of the transmission of ligand trans effects from one extreme of the molecule to the other, with the participation of the bridging hydride. Extended Hückel calculations on model diiridium complexes have suggested that such trans effect transmissions are due to the formation of molecular orbitals of sigma symmetry extended along the backbones of the complexes. This is also an expected feature for metal-metal bonded complexes. The feasibility of the transmission of ligand trans effects and trans influences through metal-metal bonds and its relevance to the understanding of both the reactivity and structures of metal-metal bonded dinuclear compounds have been substantiated through structural studies and selected reactions of the diiridium(II) complexes [Ir(2)(mu-1,8-(NH)(2)naphth)I(CH(3))(CO)(2)(P(i)Pr(3))(2)] (isomers 6 and 7) and their cationic derivatives [Ir(2)(mu-1,8-(NH)(2)naphth)(CH(3))(CO)(2)(P(i)Pr(3))(2)](CF(3)SO(3)) (isomers 8 and 9).     

Laser adiabatic manipulation of the bond length of diatomic molecules with a single chirped pulse

We propose and test numerically a scheme for controlling the bond distance in a diatomic molecule that requires the use of a single chirped pulse. The laser prepares a superposition state of both nuclear and electronic degrees of freedom, where the main character of the electronic wave function is that of an excited dissociative state. The main limitation of the scheme is the need of ultra broadband pulses, where the bandwidth must be of the order of the dissociation energy to achieve large bond elongations. The scheme can be used to deform the bond during the laser excitation to an arbitrary large and constant value, or to allow slow time-dependent bond elongations. Additionally, the scheme can be used to prepare highly excited vibrational wave packets in the ground potential after the pulse is switched off, at the expense of losing some population that dissociates. These wave packets are initially localized at the outer well of the potential, at energies controllable by the excitation process.     

High-content analysis of kinase activity in cells

High-content analysis (HCA) is a term used to describe techniques involving multiplexed analysis of fluorescent markers to measure multiple cellular responses to biological stimuli or drug treatment. HCA is usually based on automated microscopy or related technologies, and its value lies in providing multiparametric information on single cells within a population. During the last decade, several HCA approaches have been developed and applied to assess cellular mechanism of action of pharmacologically relevant compounds identified through biochemical screening or similar in vitro methods. With automation and instrument development, these approaches have evolved to the extent that the technique is now routinely used in screening applications, including primary HTS on compound collections. Here, we review the field and discuss in particular the application of HCA to the discovery of small molecule inhibitors targeting kinases which are implicated in Oncology.