Luba Tchertanov

Biomimetic Catalysis of Catechol Cleavage by O2 in Organic Solvents − Role of Accessibility of O2 to FeIII in 2,11‐Diaza[3,3](2,6)pyridinophane‐Type Catalysts

Three new complexes, [Fe(LN4H2)Cl2]+, [Fe(LN4H2)(Cat)]+, and [Fe(LN4H2)(DBC)]+, were synthesized by using the tetradentate macrocyclic ligand LN4H2 (where LN4H2, Cat, and DBC stand for 2,11-diaza[3,3](2,6) pyridinophane, catecholate, and 3,5-di-tert-butylcatecholate, respectively). The structure of [Fe(LN4H2)Cl2]+ was determined by X-ray diffraction. It crystallizes in the monoclinic space group C2/c with a = 9.613(1), b = 11.589(1), c = 14.063(2) A, β=110.20(2)°, V = 1541.9(3) A3, and Z = 4. These complexes were found to catalyze the oxidation of catechol groups using O2. This was performed in various organic solvents at 20 °C. The reaction rates were measured for the stoichiometric complexes [Fe(LN4H2)(Cat)]+ and [Fe(LN4H2)(DBC)]+. It was found that despite the relatively high energy of the ligand-to-metal charge transfer O(DBC or Cat)FeIII, their activity was comparable to that of the fast TPA systems [TPA indicates tris(2-pyridylmethyl)amine]. The oxidation products of DBCH2 have been studied. It has then been shown that the LN4H2 systems catalyse by means of both intra- and extradiol cleavage of catechol groups. The existence of multiple reactive pathways can account for the fast reactivity observed.

Mononuclear Fe(II) and Fe(III) complexes with the tetradentate ligand N,N′-bisbenzyl-N,N′-bis(2-pyridylmethyl)-ethane-1,2-diamine. Synthesis and characterisation

Abstract Two new mononuclear iron complexes, [(LBzl2)Fe(II)Cl2]·H2O and [(LBzl2) Fe(III)Cl2]·PF6, (LBzl2=N,N′-bisbenzyl-N,N′-bis(2-pyridylmethyl)-ethane-1,2-diamine) have been synthesised in view of generating complexes to mimic the active site of methane monooxygenase. Their structures have been determined by X-ray analysis. In both species, the iron atom shows a pseudo-octahedral coordination with two pyridine nitrogen atoms in axial positions and two amine nitrogen atoms in the equatorial plane. Two other equatorial positions are occupied by chloride ions. The coordination bond lengths clearly indicate the sensitivity of the ligand to the oxidation state of the iron. Thus, the FeN and FeCl bond distances in Fe(II) complex are more elongated than corresponding distances in Fe(III). A statistical examination of the bond distances of hexacoordinated Fe(II) and Fe(III) complexes using the Cambridge Structural Database provides evidence to relate both complexes to their spin state. The redox potential of the Fe(III)/Fe(II) couple was determined by cyclic voltammetry. The UV–Vis spectra are dominated by charge transfer transitions. The X-band EPR spectrum of [(LBzl2) FeCl2]·PF6 is characteristic of an S=5/2 species with an unusual zero-field splitting.

Antimitotic agents interacting with tubulin: Synthesis and structure-activity relationships of novel ortho bridged biphenyls of the rhazinilam type

Abstract Several new ortho bridged biphenyls mimicking the structure of (−)-rhazinilam were synthesized and evaluated as cytotoxic compounds and as inhibitors of microtubules disassembly. These included azadibenzo[a,c]cyclononene derivatives having an ester, urea or carbamate function present in the 9-membered ring linking the two phenyl moieties. The compound bearing a carbamate function instead of the amide group of rhazinilam interacts better with tubulin than (−) rhazinilam.

New cytotoxic flavonoids from Cryptocarya infectoria

Abstract A new dihydrochalcone, two new dihydroflavanones and eight new biflavonoids have been isolated together with cryptocaryone from the cytotoxic methanol extract of Cryptocarya infectoria. The absolute structure of cryptocaryone was established by X-ray analysis of its 8-bromo derivative. The structure of the new compounds were elucidated by spectroscopic means and their absolute stereochemistry was deduced from chemical correlation, circular dichroism data and NOESY experiments. Several compounds displayed significant cytotoxicity and cryptocaryone was shown to possess cytotoxicity towards multi-drug resistant K562-DOX cells.

A new chiral α-aminoacid with only axial dissymmetry: Synthesis and X-ray analysis of a 1,1′-binaphthyl-substituted α-aminoisobutyric acid (Bin) and of its biphenyl analogue (Bip)

Abstract Racemic as well as optically pure 1,1′-binaphthyl-substituted α-aminoisobutyric acid (Bin), a new chiral atropoisomeric α,α-disubstituted glycine, and its biphenyl analogue (Bip), have been prepared by bis-alkylation of a glycine tert-butyl ester Schiff base. The free aminoacids Bin and Bip, as well as their C-and/or N-protected derivatives have been obtained. X-ray analysis of H-Bip-OtBu and H-(S)Bin-OH is presented.

Bip: a Cα-Tetrasubstituted, Axially Chiral α-Amino Acid. Synthesis and Conformational Preference of Model Peptides

Abstract By using the recently proposed biphenyl-based, Cα-tetrasubstituted, cyclic, axially chiral α-amino acid Bip we synthesised by solution methods a large set of model peptides, including the homo-oligomer series, to the pentamer level. All of the peptides were fully characterised and their preferred conformation was assessed in solution by means of a FT-IR absorption and 1H NMR study. Results of X-ray diffraction analyses of two Bip derivatives and a terminally protected tripeptide with the sequence –Gly–Bip–Gly– are also presented. Our findings indicate that Bip tends to support β-turn and 310-helical structures, although in short peptides the fully-extended (C5) conformation would also be populated to some extent.

A Chirally Stable, Atropoisomeric,Cα-Tetrasubstitutedα-Amino Acid: Incorporation into Model Peptides and Conformational Preference

A variety of model peptides, including four complete homologous series, to the pentamer level, characterized by the recently proposed binaphthyl-based, axially chiral, Cα-tetrasubstituted, cyclic α-amino acid Bin, in combination with Ala, Gly, or Aib residues, was synthesized by solution methods and fully characterized. The solution conformational propensity of these peptides was determined by FT-IR absorption and 1H-NMR techniques. Moreover, the molecular structures of the free amino acid (S)-enantiomer and an Nα-acylated dipeptide alkylamide with the heterochiral sequence -(R)-Bin-Phe- were assessed in the crystal state by X-ray diffraction. Taken together, the results point to the conclusion that β-bends and 310 helices are preferentially adopted by Bin-containing peptides, although the fully extended conformation would also be adopted in solution by the short oligomers to some extent. We also confirmed the tendency of (R)-Bin to fold a peptide chain into right-handed bend and helical structures. The absolute configuration of the Bin residue(s) was correlated with the typically intense exciton-split Cotton effect of the 1Bb binaphthyl transition near 225 nm.

A seven-coordinate manganese(II) complex formed with the single heptadentate ligand N,N,N′-tris(2-pyridylmethyl)-N′-(2-salicylideneethyl)ethane-1,2-diamine

Abstract The new disymmetric ligand N,N,N′ -tris(2-pyridylmethyl)- N′ -(2-salicylideneethyl)ethane-1,2-diamine (LH) has been synthesized in the search of a novel type of manganese complex to mimic the active site of the water-oxidizing enzyme in photosystem II. The complex [Mn(II)L]ClO 4 has been obtained and characterized by X-ray diffraction techniques. It crystallizes in the monoclinic space group Pn with the following unit cell parameters: a =10.164(3), b =10.122(4), c =14.166(5) A, β =93.48(2)° and Z =2. The manganese ion is heptacoordinated with the coordination being achieved by only one ligand; it is bonded to the oxygen atom of the phenolate group in an axial position, the imino and the three pyridine nitrogen atoms in an equatorial position and the two amine atoms in a pseudo-axial position. The coordination polyhedron is best described as a distorted monocapped trigonal prism. This structure was compared with the seven-coordinated Mn(II) complexes deposited in the Cambridge Structured Database (CSD). The redox potential of the Mn(III)/Mn(II) couple was determined by cyclic voltammetry.

Structural metrics relationships in covalently bonded organic azides

Geometrical parameters of covalently bonded organic azides have been analysed using X-ray structural data retrieved from the Cambridge Structural Database. The RNNN fragment geometry shows some important general features: (i) a preference for a trans C(s) configuration; (ii) bending of the N-N-N unit; (iii) substantially different N-N bond lengths in the azide group. Electron-density redistribution within the covalently bonded azide group (relative to that in the isolated azide anion) promotes the capacity of the terminal azide N atom to form hydrogen bonds.

Statistical Analysis of Noncovalent Interactions of Anion Groups in Crystal Structures. III. Metal Complexes of Thiocyanate and their Hydrogen‐Donor Accepting Function

The bidentate function of the thiocyanate anion was studied using the Cambridge Structural Database System. Complexing properties (metal-thiocyanate interactions) with respect to metal cations were analysed. Two main classes were distinguished: (a) alkali and alkaline earth metals, and (b) metals of Zn and Cu groups and transition metals (group VIII). Good correlations were found between the nature of the metal (radius, oxidation state and charge) and its position relative to the thiocyanate unit. Hydrogen-bond acceptor properties of discrete and complexed SCN units were compared. The extraordinarily active hydrogenbonding behaviour allows this anion to act as a powerful bridge between different molecular fragments. In metal complexes the cation provokes a redistribution of anionic charge in SCN and the distribution of electron density, in turn, controls the hydrogen-bonding properties of the terminal acceptor atom. Binding properties of thiocyanate in biological systems were illustrated using the Brookhaven Protein Data Bank. A comparison of anion binding in small-molecule structures and in macromolecular structures shows good agreement.