Novel biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin T

Aims: To evaluate the role of novel biomarkers in early detection of acute myocardial infarction (MI) in patients admitted with acute chest pain.
Methods and results: A prospective study of 664 patients presenting to two coronary care units with chest pain was conducted over 3 years from 2003. Patients were assessed on admission: clinical characteristics, ECG (electrocardiogram), renal function, cardiac troponin T (cTnT), heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, NT-pro-brain natriuretic peptide, D-dimer, hsCRP (high sensitivity C-reactive protein), myeloperoxidase, matrix metalloproteinase-9, pregnancy associated plasma protein-A, soluble CD40 ligand. A =12 h cTnT sample was also obtained. MI was defined as cTnT = 0.03 µg/L. In patients presenting <4 h of symptom onset, sensitivity of H-FABP for MI was significantly higher than admission cTnT (73 vs. 55%; P = 0.043). Specificity of H-FABP was 71%. None of the other biomarkers challenged cTnT. Combined use of H-FABP and cTnT (either one elevated initially) significantly improved the sensitivities of H-FABP or cTnT (85%; P = 0.004). This combined approach also improved the negative predictive value, negative likelihood ratio, and the risk ratio.
Conclusion: Assessment of H-FABP within the first 4 h of symptoms is superior to cTnT for detection of MI, and is a useful additional biomarker for patients with acute chest pain.

Characterization of a ligand-attenuated binding site on glycoprotein IIb/IIIa

We describe an epitope on the platelet integrin, GPIIb/IIIa, identified by the monoclonal antibody, 4F8, which is attenuated by small-molecule GPIIb/IIIa ligands. 4F8 did not bind to the ligand binding pocket as it did not compete with a radiolabelled antagonist, H-3-SC-52012. This indicates that the 4F8 epitope behaves as a ligand-attenuated binding site (LABS). Ligand-induced attenuation of 4178 was an active process as it was prevented by pretreating platelets with cytochalasin D and reduced by prostaglandin E-1 or inhibition of protein kinase C. Disappearance of the epitope was required for full platelet activation as 4F8 prevented platelet aggregation without inhibiting fibrinogen binding. These results suggest a model where disappearance of the 4F8 epitope is a secondary event required for full

The stereoselective coordination chemistry of the helicating ligand N,N '-bis(-2,2 '-dipyridyl-5-yl)carbonyl-(S/R,S/R)-1,2-diphenylethylenediamine

Enantiomerically pure N,N'-bis(-2,2'-dipyridyl-5-yl)carbonyl-(S/R,S/R)-1,2-diphenylethylenediamine has been synthesised by linking two 2,2'-bipyridine units by (R,R)- and (S,S)-1,2-diphenylethylenediamine. The ligands possess a hindered rotation between the bipyridine chromophores, which are held together by intramolecular hydrogen bonds. ES mass spectroscopy confirmed that reaction with Fe(II), Co(III) and Cd(II) afforded dinuclear complexes. CD spectroscopy implied that enantiopure ligands conferred helicity to the metals centre giving a dominant triple helicate diastereoisomer (with the RR isomer giving a P helicate). H-1 NMR spectroscopy of the cadmium complex confirmed the presence of a single diastereoisomer. (C) 2003 Elsevier B.V. All rights reserved.

Stereoselective coordination chemistry of the tetradentate chelating ligand (2R,3R)-bis(2,2 '-dipyridyl-5-methoxyl) butane

The enantiomerically pure ligand L-3RR (2R, 3R)-bis(2,2'-dipyridyl-5-methoxyl) butane has been synthesised by linking two 2,2'-bipyridine units with (2R, 3R)-butandiol. The reaction of L-3RR with Zn(II) afforded a mononuclear species and the H-1 NMR spectroscopy points to a C-1 symmetry, expected for a distorted trigonal bipyramidal coordination environment. These observations were confirmed by MM2 calculations and electrospray mass spectrometry. The reaction of L-3RR with iron(II) indicated the formation of a dinuclear species by mass spectrometry. Solution state CD spectroscopy indicates that both complexes adopt a Lambda-configuration, implying a single stranded dinuclear iron(II) complex is present rather than the anticipated triple helical architecture.

Formation of Novel Di-Nuclear Lanthanide Luminescent Sm(III), Eu(III) and Tb(III) Triple Stranded Helicates from a C2 Symmetrically 2,6-Dicarboxylic Amide based 1,3-Xylene Ligand in CH3CN

The synthesis of the C2-symmetrical ligand 1 consisting of two naphthalene units connected to two pyridine-2,6-dicarboxamide moieties linked by a xylene spacer and the formation of LnIII-based (Ln1/4 Sm, Eu, Tb, and Lu) dimetallic helicates [Ln2 · 13] in MeCN by means of a metal-directed synthesis is described. By analyzing the metal-induced changes in the absorption and the fluorescence of 1, the formation of the helicates, and the presence of a second species [Ln2 · 12] was confirmed by nonlinear- regression analysis. While significant changes were observed in the photophysical properties of 1, the most dramatic changes were observed in the metal-centred lanthanide emissions, upon excitation of the naphthalene antennae. From the changes in the lanthanide emission, we were able to demonstrate that these helicates were formed in high yields (ca. 90% after the addition of 0.6 equiv. of LnIII), with high binding constants, which matched well with that determined from the changes in the absorption spectra. The formation of the LuIII helicate, [ Lu2 · 13 ] , was also investigated for comparison purposes, as we were unable to obtain accurate binding constants from the changes in the fluorescence emission upon formation of [Sm2 · 13], [Eu2 · 13], and [Tb2 · 13].

Ligand differentiated complementary Rh-catalyst systems for the enantioselective desymmetrization of meso-cyclic anhydrides

Two distinct systems for the rhodium-catalyzed enantioselective desymmetrization of meso-cyclic anhydrides have been developed. Each system has been optimized and are compatible with the use of in situ prepared organozinc reagents. Rhodium/PHOX species efficiently catalyze the addition of alkyl nucleophiles to glutaric anhydrides, while a rhodium/phosphoramidite system is effective in the enantioselective arylation of succinic and glutaric anhydrides.

Chromium, iron, ruthenium and gold complexes of 3,3-(biphenyl-2,2 '-diyl)-1-diphenylphosphino-1-phenylallene: A versatile ligand

Successive treatment of 9-(phenylethynyl)fluoren-9-ol (1a), with HBr, butyllithium and chlorodiphenylphosphine furnishes 3,3-(biphenyl-2,2'-diyl)-1-diphenylphosphino-1-phenylallene (5). Moreover, reaction of 1a directly with chlorodiphenylphosphine yields the corresponding allenylphosphine oxide (6). The allenylphosphine (5), and Fe-2(CO)(9) initially form the phosphine-Fe(CO)(4) complex, 11, which is very thermally sensitive and readily loses a carbonyl ligand. In the resulting phosphine-Fe(CO)(3) system, 12, the additional site at iron is coordinated by the allene double bond adjacent to phosphorus; the Fe(CO) 3 tripod in 12 exhibits restricted rotation on the NMR time-scale even at room temperature. The corresponding chromium complex, (5)-Cr(CO)5 (9), has also been prepared. The gold complexes (5)AuCl (13), and [(5)-Au(THT)](+) X-, where (THT) is tetrahydrothiophene, and X = PF6 (14a), or ClO4 (14b), are analogous to the known triphenylphosphine-gold complexes. In contrast, in the (arene)(allenylphosphine) RuCl2 system the allene double bond adjacent to phosphorus displaces a chloride, and the resulting cationic species undergoes nucleophilic attack by water yielding ultimately a five-membered Ru-P-C=C-O ruthenacycle (17). Thus, the allenylphosphine (5), reacts initially as a conventional mono-phosphine but, when the metal centre has a readily displaceable ligand such as a carbonyl or halide, the allene double bond adjacent to the phosphorus can also function as a donor. X- ray crystal structures are reported for 5, 6, 11, 12, 13, 14a, 14b and 17.

3,5-dimethyl-4-amino-1,2,4-triazole (Dat) as a tridentate ligand in the polymeric cations of [Ag-3(Dat)(2)](NO3)(3)

Colourless single crystals of [Ag-3(Dat)(2)](NO3)(3) were obtained from a reaction of silver(l) nitrate and 3,5-dimethyl-4-amino-1,2,4-triazole (Dat). In the crystal structure (orthorhombic, Fdd2, Z = 8, a = 1100.1(2), b = 3500.3(2), c = 1015.4(3) pm, R, = 0.0434) there are two crystallographically non-equivalent silver sites in a one (Ag1) to two ratio (Ag2). Both resemble linear N-Ag-N coordination although angles are 163 degrees and 144 degrees, respectively Each Dat ligand coordinates with the two ring nitrogen atoms at 216 to 219 pm and with one amino-nitrogen atom at 229 pro. According to the composition [Ag-3(Dat)(2)](3+) = [(Dat)Ag-3/2](3+), a polymeric structure is built with all Ag+ ions bridging.

Visible-light-sensitized near-infrared luminescence from rare-earth complexes of the 9-hydroxyphenalen-1-one ligand

The unique absorption properties of the 9-hydroxyphenalen-1-one (HPHN) ligand have been exploited to obtain visible-light-sensitizable rare-earth complexes in 1: 3 and 1: 4 metal-to-ligand ratios. In both stoichiometries (1:3,tris,Ln(PHN)3;1:4, tetrakis, A[ Ln( PHN)(4)], with Ln being a trivalent rare-earth ion and A being a monovalent cation), the complexes of Nd(III),Er( III), and Yb(III) show typical near-infrared luminescence upon excitation with visible light with wavelengths up to 475 nm. The X-ray crystal structures of the tris complexes show solvent coordination to the central rare-earth ion, whereas in the tetrakis complexes, the four PHN-ligands form a protective shield around the central ion, preventing small solvent molecules from coordinating to the rare-earth ion, at least in the solid state.