De novo synthesis of stable tetrahydroporphyrinic macrocycles: bacteriochlorins and a tetradehydrocorrin

[structures: see text] Bacteriochlorins (tetrahydroporphyrins) are attractive for diverse photochemical applications owing to their strong absorption in the near-infrared spectral region, as exemplified by the bacterial photosynthetic pigment bacteriochlorophyll a, yet often are labile toward dehydrogenation to give the chlorin. Tetradehydrocorrins (ring-contracted tetrahydroporphyrins) are attractive for studies of catalysis analogous to that of vitamin B12. An eight-step synthesis toward such tetrahydroporphyrinic macrocycles begins with p-tolualdehyde and proceeds to a dihydrodipyrrin-acetal (1) bearing a geminal dimethyl group and a p-tolyl substituent. Self-condensation of 1 in CH3CN containing BF3 x OEt2 at room temperature afforded a readily separable mixture of two free base bacteriochlorins and a free base B,D-tetradehydrocorrin. Each bacteriochlorin contains two geminal dimethyl groups to lock-in the bacteriochlorin hydrogenation level, p-tolyl substituents at opposing (2,12) beta-positions, and the absence (H-BC) or presence (MeO-BC) of a methoxy group at the 5- (meso) position. The B,D-tetradehydrocorrin (TDC) lies equidistant between the hydrogenation levels of corrin and corrole, is enantiomeric, and contains two geminal dimethyl groups, 2,12-di-p-tolyl substituents, and an acetal group at the pyrroline-pyrrole junction. Examination of the effect of the concentrations of 1 (2.5-50 mM) and BF3 x OEt2 (10-500 mM) revealed a different response surface for each of H-BC, MeO-BC, and TDC, enabling relatively selective preparation of a given macrocycle. The highest isolated yield of each was 49, 30, and 66%, respectively. The macrocycles are stable to routine handling in light and air. The bacteriochlorins display characteristic spectral features; for example, H-BC exhibits near-IR absorption (lambda(Qy) = 737 nm, epsilon(Qy) = 130,000 M(-1) cm(-1)) and emission (lambda(em) = 744 nm, phi(f) = 0.14). In summary, this simple entry to stable bacteriochlorins and tetradehydrocorrins should facilitate a wide variety of applications.     

Cooperative hydrogen-bonding effects in a water square: a single-crystal neutron and partial atomic charges and hardness analysis study

Four isomorphous complexes of formula [M(L)(4)(H(2)O)(2)]SO(4).2H(2)O (M = Co, 1a; Ni, 1b; Cu, 1c; Zn, 1d) have been isolated and characterized by single-crystal X-ray diffraction and neutron diffraction using the quasi-Laue diffractometer VIVALDI at the Institut Laue-Langevin as well as by thermogravimetric analysis. The structures contain a discrete, strongly hydrogen-bonded water tetramer which causes a significant distortion of the metal coordination sphere in each case. Partial atomic charges and hardness analysis (PACHA) calculations reveal that the shortest hydrogen bonds are not the strongest in this constrained, cyclic solid-state structure and show that the distortion at the metal center is caused by the drive to maintain the integrity of the water tetramer. The system undergoes a disorder-order transition on slow cooling that provides insight into the nature of communication between water squares.     

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.     

A convergent approach to huperzine A and analogues

We describe a concise and convergent synthesis of (rac)-5-methoxy-6-azatricyclco[7.3.1.0(2,7)]trideca-2(7),3,5,11-tetraen-13-ol, which has the basic ring system of huperzine A, a potent inhibitor of acetylcholinesterase. We also describe the synthesis of the novel system 5-methoxy-6-azatricyclo[7.2.2.0(2,7)]trideca-2(7),3,5-trien-10-one and a series of related systems.     

Particle circulation and oxygen mass transfer in an immobilized cell bioreactor

Two important considerations in the design of an aerobic particulate immobilized cell bioreactor are the provision of sufficient oxygen to maintain the desired metabolism of the immobilized organism, and the biomass holdup (which is proportional to the number of immobilized cell particles in the reactor). The Circulating Bed Reactor, a reactor developed for use with those forms of immobilization that result in particles of essentially neutral buoyancy, operates with an expanded bed of circulating particles. The particle number density attainable in such a reactor has been found to be dependent upon the circulation cell aspect ratio, the individual particle properties, the static bed voidage of the particles, and the superficial gas velocity. The oxygen mass transfer characteristics have been found to be dependent upon the circulatory nature of the system, the particle (solids) holdup, the particle porosity, and the superficial gas velocity.     

Estrogen receptor microarrays: subtype-selective ligand binding

We present the first example of a nuclear hormone receptor microarray, using for illustration the ligand-binding domains of the two estrogen receptors, ERalpha-LBD and ERbeta-LBD. The proteins are printed and allowed to attach to aldehyde slides; the efficiency of attachment depends on whether the LBD is liganded with agonists (low attachment) versus liganded with antagonists or unliganded (high attachment). This suggests that attachment is orientation specific and involves principally a single lysine residue. The attached ERs retain good ligand-binding activity that can be assessed using an estradiol-fluorophore conjugate, and specific and ER subtype-selective binding of ligands can be determined conveniently in competitive binding assays. This powerful new, high-throughput technique to study ligand binding to ER-LBDs can be extended to other nuclear hormone receptors and adapted to assay the recruitment of coregulator proteins.     

A cell model of a liquid droplet

An expression for the free energy of a droplet composed of attracting hard spheres is found using a simple cell model. The hard-sphere repulsion is assumed to act only between molecules in the same cell, whereas attraction extends over many cells. A maximum term analysis gives rise to a mean-field free energy which includes terms proportional to the first and second power of the droplet radius R with coefficients which can be related to the planar surface tension and Tolman length. Certain Gaussian fluctuations about the maximum term are also considered, corresponding to droplet translation and capillary wave fluctuations. Inclusion of these fluctuations is necessary to ensure that the nucleation rate is proportional to the system volume. They also reduce the planar surface tension and introduce a logarithmic term, -4/3 ln R, into the free energy. The inclusion of other fluctuations and the relationship between these equations and those arising in density-functional theories of nucleation is discussed.     

Metallaborane reaction chemistry. A facile and reversible dioxygen capture by a B-frame-supported bimetallic: structure of [(PMe2Ph)4(O2)Pt2B10H10

[(PMe2Ph)4Pt2B10H10] reversibly takes up atmospheric dioxygen to give the fluxional dioxygen-dimetallaborane complex [(PMe2Ph)4(O2)Pt2B10H10], which has Pt-Pt 2.7143(3), Pt-O 2.141(4) and 2.151(4) and O-O 1.434(6)A.     

Stereocontrol in Organic Synthesis Using the Diphenylphosphoryl Group

In 1959, Horner showed that metalated alkyldiphenylphosphane oxides react with aldehydes or ketones to give alkenes. With this reaction, the diphenylphosphoryl (Ph₂PO) group made its entrance into synthetic organic chemistry. In the thirty-six years since that date, extensive research has shown that this olefination, the Horner–Wittig reaction, has unique properties that make it much more than simply the phosphane oxide cousin of the more famous phosphorus-based olefinations—the Wittig reaction (based on phosphonium salts) and the Wadsworth–Emmons reaction (based on phosphonate esters). Early work on the Horner–Wittig reaction concentrated on the reactivity of phosphane oxides and the regioselectivity of their reactions, but more recently the power of the Ph₂PO group to control the stereochemistry of alkenes, and to produce “on demand” either stereoisomer in high stereochemical purity, has emerged. From the study of these stereocontrolled Horner–Wittig reactions arose the realization that the Ph₂PO group is useful not only for the control of the two-dimensional stereochemistry of alkenes, but also of three-dimensional stereochemistry in general. After a brief introduction to phosphane oxide chemistry, this review will examine the Horner–Wittig reaction, in both its original and “stereocontrolled” varieties. From there, we will move on to an account of the stereoselective construction of molecules containing the Ph₂PO group, concentrating on the stereochemical directing effects of the Ph₂PO group and on the role of its unique combination of attributes—steric bulk, electronegativity, and Lewis basicity—in controlling these reactions. Finally, we will present what is intended as a practical guide to this chemistry, covering the type of functionalized alkenes that have been made with the help of the Ph₂PO group and giving guidelines that we hope will help the organic chemist to make the most of the chemistry the Ph₂PO group has to offer.     

A sequential molecular mechanics/quantum mechanics study of the electronic spectra of amides

We report gas-phase electronic spectra of formamide, N-methyformamide, acetamide, and N-methylacetamide at 300 K calculated using a combination of classical molecular dynamics and time-dependent density functional theory (TDDFT). In comparison to excitation energies computed using the global minima structures, the valence npi* and pi(nb)pi* states show a significant red-shift of 0.1-0.35 eV, while smaller shifts are found for the n3s and pi(nb)3s Rydberg states. In this work, we have identified the physical origin of these shifts arising from variations of the molecular structure. We present simple relationships between key geometrical parameters and spectral shifts. Consequently, electronic spectra can be generated directly from ground-state structures, without additional quantum chemical calculations. The electronic spectrum of formamide in aqueous solution is computed using TDDFT using an explicit solvent model. This provides a quantitative determination of the condensed-phase spectrum. In general, this study shows that temperature effects can change the predicted excitation energies significantly and demonstrates how electronic spectra at elevated temperatures can be computed in a computationally efficient way.