Tetra-porphyrin molecular tweezers: two binding sites linked via a polycyclic scaffold and rotating phenyl diimide core.

The synthesis of a tetra-porphyrin molecular tweezer with two binding sites is described. The bis-porphyrin binding sites are aligned by a polycyclic scaffold and linked via a freely rotating phenyl diimide core. Synthesis was achieved using a divergent approach employing a novel coupling method for linking two polycyclic units to construct the core, with a copper(ii)-mediated phenyl boronic acid coupling found to extend to our polycyclic imide derivative. We expect this chemistry to be a powerful tool in accessing functional polycyclic supramolecular architectures in applications where north/south reactivity and/or directional interactions between modules are important. Porphyrin receptor functionalisation was undertaken last, by a four-fold ACE coupling reaction on the tetra-epoxide derivative of the core.

L-histidine methyl ester dihydrochloride.

The title compound, C7H13N3O2(2+).2Cl-, has distances and angles quite similar to those of histidine hydrochloride monohydrate [Donohue & Caron (1964). Acta Cryst. 17, 1178-1180], except for the distances within the ester functionality.

Investigations of glutathione conjugation in vitro by 1H NMR spectroscopy. Uncatalyzed and glutathione transferase-catalyzed reactions.

Conjugation reactions of glutathione (GSH) and related thiols with diethyl maleate (DEM) and other alpha, beta-unsaturated carbonyl compounds have been investigated by 1H NMR spectroscopy. The products from the reaction with DEM and diethyl fumarate (DEF) are shown to be the diastereomers of S-(alpha,beta-diethoxycarbonylethyl)glutathione. During the course of the reaction, DEM isomerized to DEF, and the rate of isomerization was dependent upon whether the solvent was 1H2O or 2H2O. The observed rate data exhibit apparent second order kinetic behavior. The reaction of maleate with GSH was considerably slower, and solvent-dependent isomerization was observed, while little reaction of fumarate with GSH was observed at pH 6.5. Reaction of DEM with N-acetyl-L-cysteine followed a similar course to that of GSH, and although L-cysteine reacted rapidly with DEM, it did not promote the isomerization of DEM. Reactions involving penicillamine and N-acetylpenicillamine were considerably slower. Conjugation reactions catalyzed by commercial GSH transferases and selected rat and human purified isoenzymes were also investigated. Of those isoenzymes studied, rat GSH transferase 4-4 was found to exert the greatest degree of stereo control in conjugation reactions with DEF.

Tris[(2-pyridinium)methyl]amine perchlorate.

Nitrilotrismethylenetri-2-pyridinium perchlorate, C18H21N4(3+).3C1O4-, Mr = 591.74, cubic, P2(1)3, a = 13.289 (3) A, V = 2347 (2) A 3, Z = 4, Dx = 1.675 (2) g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 4.60 cm-1, F(000) = 1216, T = 189 (3) K, R = 0.056 for 1073 unique observed reflections with I greater than sigma(I). All four ions lie on threefold axes. The perchlorate ions are nearly regular tetrahedra. The bond lengths and angles in the ions are normal. As the name implies, the cation is protonated on the pyridine N atoms and not on the amine N atom. Each H atom attached to an N atom is part of a three-centered hydrogen bond in which the H-atom acceptors are O atoms on two different perchlorate ions.

Factors affecting 1H NMR spectra of blood plasma: cancer, diet and freezing.

Single pulse and Hahn spin-echo 400 and 500 MHz 1H NMR spectra from normal subjects and cancer patients are reported. No significant difference was found between the average -CH3 and -(CH2)n- lipoprotein linewidths of the two groups in contrast to a previous report. Such measurements are shown to be complicated by freezing and thawing of samples which broadens lipoprotein resonances, and by eating which sharpens them. Deconvolution of the composite lipoprotein signals enables these effects to be interpreted. Other notable features of plasma spectra are discussed including resonances for 'acute-phase' glycoproteins, ketone bodies and other small molecules.

Coordination chemistry in biological media: reactions of antitumor Pt(II) and Au(III) complexes with cell culture media.

Reactions of cis-PtCl2(NH3)2 (1), Pt(1,2-diaminoethane)Cl2 (2), PtCl4(2-) (3), and AuCl4- (4) with intact cell culture media have been studied by spin-echo 500 MHz proton NMR spectroscopy. This has allowed us to observe reactions of components of the media at submillimolar concentrations. Upon the addition of 400 microM 1, 2, or 3 to the media, the S-methyl peak of methionine decreases in intensity and in each case a new peak appears which we have tentatively assigned to the S-CH3 of Pt(N,S-L-Met)2. In the spectra of the media with 2, an additional peak appears, assignable to the S-CH3 of Pt(1,2-diaminoethane)(N,S-L-Met). Upon the addition of Au(III) to the media, the S-CH3 peak of methionine also decreases in intensity and new peaks appear in the 2.6 to 2.8 ppm region, including a peak identified as the S(O)-CH3 peak of methionine sulfoxide. The other peaks are assignable to Au(I)-S(Met) species. Practical methods of following the reactions of metal complexes in cell culture media are becoming of wider significance with the increasing use of cell cultures for drug screening instead of animal tests.

The autoxidation and proton dissociation constants of tertiary diphosphines: relevance to biological activity.

The pKas and autoxidation properties of a number of diphosphines which exhibit varying degrees of antitumor and cytotoxic activity were investigated. Titration by HClO4 in CH3NO2 was used to determine pKas of the following diphosphines: R2P(CH2)nPR'2, where for R = R' = Ph, n = 1, 2, and 3 (dppm, dppe, and dppp respectively); for R = R' = Et, n = 2 (depe); for R = Ph, R' = Et, n = 2 (eppe); and for cis and trans Ph2PCH = CHPPh2 (dppey). The difference between the first and second protonation constants decreases as the length of the carbon chain between the two phosphorus centers increases. Unsaturation in the carbon chain lowers pKas. -PEt2 centers are apparently more basic than -PPh2 centers. Apart from electrostatic effects, the protonation of a given phosphine center appears to be independent of the substituents at the second phosphine center. The autoxidation reactions of dppm, dppe, dppp, depe, and cis-dppey were studied in a variety of solvents by 31P NMR spectroscopy. The ethyl-substituted diphosphines were much more rapidly oxidized than the phenyl-substituted, and the pathways of autoxidation differed. Generally, the phenyl-substituted diphosphines gave only mono- and dioxides, while the ethyl-substituted diphosphines additionally gave phosphinites and other oxidation products. The relevance of the autoxidation reactivity and the pKas to the contrasting antitumor activity of these diphosphines is discussed.