BackgroundRapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic.Methods/designThe SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014.DiscussionThis is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease.Trial registrationClinicalTrials.gov Identifier: NCT01149590

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Reaction of 2-mercapto-1-methylimidazole (methimazole) with tris(dimethylamino)borane, B(NMe2)3, provides the tetrahedral dimethylamine adduct of tris(methimazolyl)borane, [(Me2HN)B(methimazolyl)3]. By contrast, imidazole, 2-methylimidazole, 2-chloroimidazole and benzimidazole provide the homoleptic tetra-azolyl systems H[B(azolyl)4], and the same product is obtained even when a substoichiometric quantity of the heterocyle is employed. The change in reaction outcome is correlated with the variation of basic pKa for the heterocycles. A simple acid-base reaction with elimination of HNMe2 is proposed for the reaction with the weakly basic, but more strongly acidic, methimazole. However, for the more strongly basic imidazoles, initial coordination of the heterocycle imine nitrogen to the weakly Lewis acidic boron centre in B(NMe2)3 to form the tetrahedral adduct [(azole)B(NMe2)3] is proposed. The greater availability of the NMe2 lone pairs in this species results in increased basicity and a rapid reaction with further heterocycle to provide the observed H[B(azolyl)4] products. For 2-nitroimidazole, the low basicity (and increased N-H acidity) results in the formation of [(HNMe2)B(2-nitroimidazolyl)3] on reaction with B(NMe2)3, analogous to the product formed with methimazole. Both [(HNMe2)B(methimazolyl)3] and H[B(benzimidazolyl)4] have been structurally characterised by single crystal X-ray crystallography. This chemistry has been exploited to provide a new synthesis of borate-centred tripod ligands, whereby N-methylimidazole is used to activate B(NMe2)3 to reaction with methimazole to form the new ligand [(N-methylimidazole)B(methimazolyl)3] in good yield and a complex of this ligand with Ru(II) has been structurally characterised.

The tripodal ligands hydrotris(N-ethyl-2-mercaptoimidazol-1-yl)borate (NaTm(Et)) (1) and hydrotris(N-benzyl-2-mercaptoimidazol-1-yl)borate (NaTm(Bn)) (2), analogues of the hydrotris(N-methyl-2-mercaptoimidazol-1-yl)borate ligand (Tm) containing alternative nitrogen substituents, have been employed to examine the racemization of their C3-symmetric complexes with both four- and six-coordinate metals. The ligands react at room temperature with metal halides to provide C3-symmetric metal complexes. The syntheses of the four-coordinate complexes [Tm(Et)ZnCl] (3), [Tm(Et)CdBr] (4), [Tm(Et)HgCl] (5), [Tm(Et)CuPPh3] (6), [Tm(Et)AgPPh3] (7), and [Tm(Bn)ZnCl] (8) are reported. The six-coordinate complexes [Tm(Et)Ru(p-cymene)]Cl (9), [Tm(Et)Ru(p-cymene)]PF(6) (10), and [Tm(Et)Mn(CO)3] (11) were also synthesized. The X-ray crystal structures of 3, 4, 6, and 9 are reported. The diastereotopic nature of the ethyl and benzyl hydrogen atoms in the ligands allows the enantiomeric forms of these complexes to be distinguished by 1H NMR spectroscopy. Variable-temperature (VT) 1H NMR spectra have thus been used to investigate the energies of the racemization processes occurring in these chiral complexes. In solvents the activation energies to racemization for the four-coordinate complexes lay in the range of 53-77 kJ mol(-1). In non-donor solvents the energies are reduced and a dissociative mechanism is therefore implicated. No interconversion could be observed by VT NMR for the six-coordinate complexes in any solvent. To further explore the racemization mechanisms ab initio density functional theory calculations have been conducted on the ground- and transition-state structures of representative six-coordinate [Mn(I)] and four-coordinate [Zn(II)] complexes following a proposed nondissociative mechanism of racemization. The calculated energy barriers to racemization are 163 and 121 kJ mol(-1), respectively. It is concluded that the low-energy racemization of substitution-labile four-coordinate complexes occurs via a dissociative mechanism, while substitution-inert six-coordinate complexes experience a significantly higher barrier to racemization. Whether this is due to the operation of a dissociative mechanism with a higher activation barrier or to a nondissociative mechanism remains unknown.