Frank T. Edelmann

N-silylated benzamidines: versatile building blocks in main group and coordination chemistry

Abstract The main group and coordination chemistry of N-silylated benzamidines, RC 6 H 4 C(NSiMe 3 )[N(SiMe 3 ) 2 ], and the corresponding anions, [RC 6 H 4 C(NSiMe 3 ) 2 ] − , is reviewed. Lithium and sodium salts of the type M[RC 6 H 4 C(NSiMe 3 ) 2 ] (MLi, Na) are easily accessible via addition of LiN(SiMe 3 ) 2 or NaN(SiMe 3 ) 2 to various substituted benzonitriles. Subsequent reactions with Me 3 SiCl lead to the fully silylated benzamidine derivatives. Both the neutral species and the anions are highly useful precursors in main group chemistry, for example, for the preparation of various inorganic heterocycles. They also react with transition metal halides to give in most cases benzamidinato chelate complexes containing planar, four-membered MNCN rings. Other reaction pathways include the formation of transition metal amido, imido, nitrido, and hydrazido complexes. In some cases hydrolytic cleavage of one or more SiN bonds is observed. The silylated benzamidinate anions [RC 6 H 4 C(NSiMe 3 ) 2 ] − are especially useful as novel observer ligands for f-elements. They form low-coordinate, hydrocarbon-soluble complexes with lanthanide and actinide elements.

Supramolecular Organometallic Chemistry

Basic Concepts and Principles. Molecular Recognition and Host-Guest Interactions. Supramolecular Self-Assembly by Dative Bonds (Electron-Pair Donor-Acceptor or Lewis Acid-Base Interactions). Supramolecular Self-Assembly by Formation of Secondary Bonds. Supramolecular Self-Assembly by Hydrogen-Bond Interactions. Supramolecular Self-Assembly Caused by Ionic Interactions. Supramolecular Self-Assembly as a Result of PI-Interactions. Subject Index.

New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes

The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.

Enhanced Detection of Paroxysmal Atrial Fibrillation by Early and Prolonged Continuous Holter Monitoring in Patients With Cerebral Ischemia Presenting in Sinus Rhythm

Background and Purpose Diagnosis of paroxysmal atrial fibrillation is difficult but highly relevant in patients presenting with cerebral ischemia yet free from atrial fibrillation on admission. Early initiation and prolongation of continuous Holter monitoring may improve diagnostic yield compared with the standard of care including a 24-hour Holter recording. Methods— In the observational Find-AF trial (ISRCTN 46104198), consecutive patients presenting with symptoms of cerebral ischemia were included. Patients free from atrial fibrillation at presentation received 7-day Holter monitoring. Results— Two hundred eighty-one patients were prospectively included. Forty-four (15.7%) had atrial fibrillation documented by routine electrocardiogram on admission. All remaining patients received Holter monitors at a median of 5.5 hours after presentation. In those 224 patients who received Holter monitors but had no previously known paroxysmal atrial fibrillation, the detection rate with early and prolonged (7 days) Holter monitoring (12.5%) was significantly higher than for any 24-hour (mean of 7 intervals: 4.8%, P=0.015) or any 48-hour monitoring interval (mean of 6 intervals: 6.4%, P=0.023). Of those 28 patients with new atrial fibrillation on Holter monitoring, 15 (6.7%) had been discharged without therapeutic anticoagulation after routine clinical care (ie, with data from 24-hour Holter monitoring only). Detection rates were 43.8% or 6.3% for short supraventricular runs of ≥10 beats or prolonged episodes (<5 hours) of atrial fibrillation, respectively. Diagnostic yield appeared to be only slightly and not significantly increased during the first 3 days after the index event. Conclusions— Prolongation of Holter monitoring in patients with symptoms of cerebral ischemic events increases the rate of detection of paroxysmal atrial fibrillation up to Day 7, leading to a relevant change in therapy in a substantial number of patients. Early initiation of monitoring does not appear to be crucial. Hence, prolonged Holter monitoring (≥7 days) should be considered for all patients with unexplained cerebral ischemia.

Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS‐ELD trial

Various beta‐blockers with distinct pharmacological profiles are approved in heart failure, yet they remain underused and underdosed. Although potentially of major public health importance, whether one agent is superior in terms of tolerability and optimal dosing has not been investigated. The aim of this study was therefore to compare the tolerability and clinical effects of two proven beta‐blockers in elderly patients with heart failure.

Disiloxanediolates and polyhedral metallasilsesquioxanes of the early transition metals and f-elements

Abstract Two modern areas of metallasiloxane chemistry are reviewed. The first part deals with the preparation and structural characterization of the first f-element compounds derived from tetraphenylsisiloxanediol. In the second part recent developments in the chemistry of polyhedral metallasilsesquioxanes are surveyed, with special emphasis being placed on early transition metal and f-element derivatives. Also highlighted are applications of these species in catalysis research.

Blunted frequency-dependent upregulation of cardiac output is related to impaired relaxation in diastolic heart failure

Aims We tested the hypothesis that, in heart failure with normal ejection fraction (HFNEF), diastolic dysfunction is accentuated at increasing heart rates, and this contributes to impaired frequency-dependent augmentation of cardiac output. Methods and results In 17 patients with HFNEF (median age 69 years, 13 female) and seven age-matched control patients, systolic and diastolic function was analysed by pressure–volume loops at baseline heart rate and during atrial pacing to 100 and 120 min−1. At baseline, relaxation was prolonged and end-diastolic left ventricular stiffness was higher in HFNEF, whereas all parameters of systolic function were not different from control patients. This resulted in smaller end-diastolic volumes, higher end-diastolic pressure, and a lower stroke volume and cardiac index in HFNEF vs. control patients. During pacing, frequency-dependent upregulation of contractility indices (+dP/dtmax and Ees) occurred similarly in HFNEF and control patients, but frequency-dependent acceleration of relaxation (dP/dtmin) was blunted in HFNEF. In HFNEF, end-diastolic volume and stroke volume decreased with higher heart rates while both remained unchanged in control patients. Conclusion In HFNEF, frequency-dependent upregulation of cardiac output is blunted. This results from progressive volume unloading of the left ventricle due to limited relaxation reserve in combination with increased LV passive stiffness, despite preserved force–frequency relation.

Transition-metal complexes of inorganic sulphur-nitrogen ligands

Complexes des nitrures de soufre, des halogenures de thiazyle, des oxydes de soufre et azote, des imides soufres

Organoactinoid-Komplexe : Substituierte Benzamidinat-Anionen als sterische Äquivalente zu η5-C5H5 und η5-C5Me5. Molekülstrukturen von [PhC(NSiMe3)2]3UCl, [4-CF3C6H4C(NSiMe3)2]3UCl, [2,4,6-(CF3)3C6H2C(NSiMe3)2]2UCl2 und [2,4,6-(CF3)3C6H2C(NSiMe3)2]2ThCl2

The reaction of substituted benzonitrile derivatives with LiN(SiMe3)2 or NaN(SiMe3)2 yields N,N′-bis(trimethylsilyl)benzamidinates Li[RC6H4C(NSiMe3)2] (1) and Na[RC6H4C(NSiMe3)2] (2) (R = H, Me, OMe, CF3) respectively. 2,4,6-Trisubstituted derivatives, Li[R3C6H2C(NSiMe3)2] (3: R = CF3, 4: R = Me) are available by addition of R3C6H2Li to Me3SiNCNSiMe3. The N,N′-bis(trimethylsilyl)benzamidinate anions can be regarded as steric equivalents of η5-C5H5 and η5-C5Me5. The alkali metal derivatives 1 and 2 react with UCl4 to give substituted benzamidinato-uranium(IV) chlorides. Depending on the stoichiometry, complexes of the type [RC6H4C(NSiMe3)2]2UCl2 (5) and [RC6H4C(NSiMe3)2]3UCl (6) can be isolated. Sterically more demanding ligands [R3C6H2C(NSiMe3)2]− give exclusively the disubstituted products [R3C6H2C(NSiMe3)2]2UCl2 (7: R = CF3, 8: R = Me). The thorium(IV) complexes [(CF3)3C6H2C(NSiMe3)2]2ThCl2 (9) and [CF3C6H4C(NSiMe3)2]3ThCl (10) can similarly by synthesized. The structures of [PhC(NSiMe3)2]3UCl (6a), [4-CF3C6H4C(NSiMe3)2]3UCl (6d), [2,4,6-(CF3)3C6H2C(NSiMe3)2]2UCl2 (7) and [2,4,6-(CF3)3C6H2C(NSiMe3)2]2ThCl2 (9) were determined by X-ray crystallography.

MONO-ETA-CYCLOPENTADIENYL-BENZAMIDINATO CHLORO COMPOUNDS OF TITANIUM, ZIRCONIUM AND HAFNIUM

The new compounds {M(eta-C(5)R(5))[eta-CPh(NSiMe(3))(2)]]Cl-2} (where R = H, M = Ti, Zr, Hf or R = Me, M = Ti or Zr), are described. The crystal structures of {M(eta-C(5)R(5))([eta-CPh(NSiMe(3))(2)]Cl-2} (R = H, M = Zr or Hf) have been determined. The compound {Zr(eta-C5H5)[eta-CPh(NSiMe(3))(2)]Cl-2} acts as a co-catalyst for the polymerisation of ethylene and propene.