Non-Covalent Lanthanide Podates with Predetermined Physicochemical Properties: Iron(II) Spin-State Equilibria in Self-Assembled Heterodinuclear d-f supramolecular Complexes.

The reaction of the segmental compound 2-[6-(diethylcarbamoyl)pyridin-2-yl]-1,1-dimethyl-2-(5- methylpyridin-2-yl)-5,5-methylenebis(1H-benzimidazole) (L) with a stoichiometric mixture of FeII and LnIII (Ln = La, Nd, Eu, Gd, Tb, Yb, Lu, Y or Sc) or CaII in acetonitrile produced selectively the heterodinuclear non-covalent podates [LnFeL3]5+ and [CaFeL3]4+. Proton NMR and electronic spectroscopy and electrochemistry showed that the ligands are helically wrapped around the metal ions leading to a C3-triple-helical structure with FeII occupying the pseudo-octahedral co-ordination site produced by the three bidentate binding units and LnIII lying in the remaining pseudo-tricapped trigonal-prismatic site defined by the three tridentate binding units. In this chemical environment FeII sustains a thermally induced low-spin high-spin transition around room temperature in acetonitrile, the thermodynamic parameters of which can be finely controlled by the size of the co-ordinated LnIII. Thermodynamic investigations of the assembly process suggest that the stability of the final complexes [LnFeL3]5+ depends on the size of LnIII, small metal ions leading to intricate mixtures of complexes. The crystal structure of [LaFeL3][ClO4]0.5[CF3SO3 ]4.5·MeCN·4H2O at 170 K is isostructural with that of [EuZnL3][ClO4][CF3SO3]4 · 4MeCN and indicates that (i) the Fe–N bonds are in the range expected for essentially low-spin FeII and (ii) [LaFeL3]5+ adopts the regular triple-helical structure found in solution. Magnetic measurements in the solid state showed smooth spin transitions similar to those observed in solution, while photophysical studies suggested that EuIIIFeII (low-spin) energy transfers are responsible for the complete quenching of the Eu-centred emission

Cancer chemopreventive diterpenes from Salvia corrugata

NMR and NP-HPLC-UV profiling of the exudate of Salvia corrugata revealed that its secondary metabolite composition was largely dominated by a-hydroxy-b-isopropyl-benzoquinone diterpenoids. Among them, four diterpenes not described previously were isolated and identified as fruticulin C (3), 7a-methoxy-19- acetoxy-royleanone (4), 7a,19-diacetoxy-royleanone (5), and 7-dehydroxy-conacytone (7). In addition, the known diterpenes fruticulin A (1), demethyl-fruticulin A (2) and 7a-O-methyl-conacytone (6) were also obtained. The isolated compounds were evaluated for their cancer chemopreventive activity by measuring quinone reductase induction activity and histone deacetylase inhibition. Three compounds (1, 2 and 5) showed promising activity

Structural features for HDAC6 inhibitory specificity of Salvia corrugata Vahl. diterpene \u3b1-hydroxyquinones

Histone deacetylases (HDACs) are enzymes that deacetylate lysine residues from histones as well as from several other nuclear, cytoplasmic and mitochondrial non-histone proteins. In mammals, 11 zinc-dependent HDACs have been classified into three classes: Class I (HDACs 1 to 3 and HDAC8), class II which is subdivided into classes IIa (HDAC4, 5, 7, and 9) and IIb (HDAC6and 10), and class IV (HDAC11) [1]. Because of its central role in memory, protein aggregate elimination, neuronal oxidative stress and mitochondrial functions, HDAC6 appears as a promising target for Alzheimer's disease [1, 2]. However, developing new selective HDAC6 inhibitors is a challenge and their design is usually based on structural modifications on the cap portion, which is separated from a zinc-binding group by a linker portion [2]. Aims: To search for potential structural features within natural scaffolds which are able to provide isoform inhibitory specificity for HDAC6 compared to class I HDACs