Crystal engineering: Supramolecular structures by cocrystallization ofMeso-1,2-diphenyl-1,2-ethanediol and bisimines,simple cases of molecular recognition

The crystal structures of molecular complexes betweenmeso- 1,2-diphenyl-1,2-ethanediol and two bisimines (N,N-(dibenzylidene)-ethylenediamine and glyoxylidene-bis(2,4-dimethyl-3-pentyl-amine) are reported at different temperatures. The structure-determining motif of the cocrystalline arrangement is one single O-H . N hydrogen bond resulting in infinite ladderlike polymers. The supramolecular structure is formed by recognition of fitting species: Thed- orl-isomers do not arrange in such structures.¹H NMR experiments show that no prearrangements take place by forming complexes in solution.     

Synthesis,spectroscopic and electrochemical studies of mixed ligand ruthenium(II) chiral Schiff base complexes with nitrogen donors

Summary Mixed ligand complexes (1)-(18) of composition [RuL-(PPh₃)Y] and [RuL(PPh₃)(H₂O)Y]^- (L = chiral Schiff bases derived from l-alanine, l-valine, l-serine, l-cystein, l-arginine or l-aspartic acid with salicylaldehyde; Y = azide, 2,2-bipyridyl or 1,10-phenanthroline) have been prepared and characterized by microanalysis, spectroscopy and polarography. The conformational aspects regarding the relationship of the asymmetric carbon atom to the nitrogen donors around the Ru^II are discussed. All complexes showed quasi-reversible c.v. behaviour and the redox potentials of the Ru^II/Ru^I couple lie in the -0.31 to-0.16 V range.     

Functionality map analysis of the active site cleft of human thrombin

Summary The Multiple Copy Simultaneous Search methodology has been used to construct functionality maps for an extended region of human thrombin, including the active site. This method allows the determination of energetically favorable positions and orientations for functional groups defined by the user on the three-dimensional surface of a protein. The positions of 10 functional group sites are compared with those of corresponding groups of four thrombin-inhibitor complexes. Many, but not all features, of known thrombin inhibitors are reproduced by the method. The results indicate that certain aspects of the binding modes of these inhibitors are not optimal. In addition, suggestions are made for improving binding by interaction with functional group sites on the thrombin surface that are not used by the thrombin inhibitors. Abbreviations: MCSS, multiple copy simultaneous search; PPACK, d-phenylalanyl-l-propyl-l-arginine chloromethane; NAPAP, N -(2-naphthylsulfonylglycyl)-d-para-amidinophenylalanylpiperidine; argatroban, (2R,4R)-4-methyl-1-[N -(3-methyl-1,2,3,4-tetrahydro-8-quinolinylsulfonyl)-l-arginyl]-2-piperidine carboxylic acid; rms, root mean square. The thrombin residues are numbered according to the chymotrypsin-based numbering by Bode et al. [8]. P1, P2, P3, etc., denote the peptide inhibitor residues on the amino-terminal side of the scissile peptide bond, and S1, S2, S3, etc., the corresponding subsites of thrombin     

Synthesis and properties of some chromium(III) β-diketonate complexes

Summary Equimolar quantities of CrCl₃ · 3THF and-diketones, -dkH, react to yield CrCl₂(-dk) · 2THF and CrCl₂(-dk) · THF complexes in coordinating and noncoordinating solvents respectively. For 1 : 2 and 1 : 3 molar ratios of reactants, derivatives of general formulae CrCl(-dk)₂ and Cr(-dk)₃ (where-dkH = acerylacetrrnc, benzoylacetonc and dibenzoylmethane) have been isolated. All complexes have been characterized by elemental analysis, molecular weights and by i.r. spectra.     

Coordination complexes of l-azetidine-2-carboxylic acid with platinum(II) and palladium(II)

Summary The complexes K[Pt(l-aze)Cl₂, [Pt(l-aze)₂] and [Pd(l-aze)₂] (l-aze = l-azetidine-2-carboxylate) were prepared. X-ray structures show that [Pt(l-aze)₂] and [Pd(l-aze)₂] are isomorphous, having a planar tetragonal geometry with a trans configuration around the Pt and Pd atoms. Slight puckerings of the MN(1)N(11)O(11) chelate ring (M = Pt or Pd) and the azetidine ring were observed. The circular dichroism (c.d.) spectra of the complexes in aqueous solution agree with the structures found in the solid state as far as the hexadecant rule is concerned, giving, for the trans configuration of [M(l-ia)₂] (where ia = imino acid), the profile of the c.d. signs for the three predominant d-d transitions as: +,-,-. I.r., conductivity and n.m.r. measurements are also reported and are in accord with the proposed structures.     

Reactions of 2-pyridylphenylacetonitrile and 1,2-dicyano-1,2-di(phenyl)-1,2-di(2-pyridyl)ethane with titanium(IV), vanadium(IV), chromium(III) and iron(III) chlorides

Summary 2-Pyridylphenylacetonitrile (ppa) is oxidized by iron(III) chloride in dry ethanol to 1,2-dicyano-1,2-di(phenyl)-1,2-(2-pyridyl)ethane (dcppe). When 1,2-dichloroethane or ether are used as solvents, a 31 complex of dcppe with iron trichloride, [(FeCl₃)₃(dcppe)] is obtained.Titanium(IV), vanadium(IV) and chromium(III) chlorides react with ppa and dcppe, giving complexes of general formulae [MCl₄(ppa)] (M = Ti or V), [CrCl₃(ppa)_n] (n = 2 or 3), [(MCl₄)₂(dcppe)] (M = Ti or V) and [CrCl₃(dcppe)].     

Mechanistic investigations on the oxidation of <Emphasis Type="SmallCaps">l</Emphasis>-valine by diperiodatocuprate(III) in aqueous alkaline medium: a kinetic model

The oxidation of l-valine (l-val) by diperiodatocuprate(III) (DPC) in aqueous alkaline medium at a constant ionic strength of 3.0 × 10⁻³ mol dm⁻³ was studied spectrophotometrically at 298 K and follows the rate law;

Products and kinetics of the thermal decomposition of (l-(−)-menthyl)[2,2′-methylene-bis-(4-methyl-6-tert-butylphenyl)] phosphite ozonide

Two conformers (chair, boat) of [l-(–)-menthyl)]-[2,2-methylene-bis-(4-methyl-6-tert-butylphenyl)] phosphite ozonide have been obtained by the low temperature ozonization (–80 °C) of [l-(–)-menthyl)]-[2,2-methylene-bis-(4-methyl-6-tert-butylphenyl)] phosphite. It was determined that decomposition of the ozonide is first order with the rate constant logk ₀ = (10.92±1.10)–(14.02±1.25)/gq ( = 2.303RT, kcal mol^–1), leading to [l-(–)-menthyl)]-[2,2-methylene-bis-(4-methyl-6-tert-butylphenyl)] phosphate and oxygen (including singlet oxygen). Conformational transitions (chair-boat) for [l-(–)-menthyl)]-[2,2-methylene-bis-(4-methyl-6-tert-butylphenyl)] phosphate have been registered by³¹P NMR spectroscopy.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1758–1761, October, 1994.This work was supported by Russian Foundation for Basic Research (Project No. 93-03-532l).     

Flow injection chemiluminescence determination of l-cysteine in amino acid mixture and human urine with the BrO3 −–quinine system

In this paper, a novel flow injection chemiluminescence (CL) determination of l-cysteine is proposed. The method is based on the CL reaction of l-cysteine and KBrO₃ in acidic medium. The CL intensity was greatly enhanced in the presence of quinine. The CL intensity was linear with l-cysteine concentration in the range of 0.2–80 g L^–1, and the detection limit was 0.1 g L^–1 (3). A complete analysis, including sampling and injecting, could be performed in 1 min, giving a throughput of about 60 h^–1. The relative standard deviation was 1.6% for 0.8 g L^–1 l-cysteine (n=11). The proposed method was satisfactorily applied to the determination of cysteine in an amino acid mixture and human urine. The mechanism of the CL reaction is also discussed.     

l-Lactat-Durchflu?elektrode mit immobilisierter Lactat-Oxidase

Zusammenfassung Eine leicht zu handhabende l-Lactat-Durchflußelektrode mit immobilisierter Lactat-Oxidase wird beschrieben. Sie ist Bestandteil eines dreikanaligen O₂-sensitiv-enzymatischen Meßsystems für l-Lactat, Pyruvat und -d-Glucose. Der l-Lactat-Sensor weist eine schnelle Einstellzeit, geringe Streuung um die errechnete Regressionsgerade und einen für die klinisch-chemische Analytik adäquaten linearen Anzeigebereich auf. Meßkurven werden demonstriert. Auf den Chemismus anderer üblicher elektrochemisch-enzymatischer Meßverfahren von l-Lactat wird hingewiesen und auf die klinische Bedeutung der l-Lactat-Bestimmung Bezug genommen.

---

l-lactate flow-through electrode with immobilized lactate oxidase

Summary An l-lactate flow-through electrode with immobilized lactate oxidase is described that is easy to handle. It is part of a three-channel O₂-sensitive enzymatical measuring system for l-lactate, pyruvate and -d glucose. The l-lactate sensor features a short response time, little variation about the regression line computed and a linear indicating range adequate for clinical-chemical analysis. Measurement diagrams are demonstrated. The chemism of other conventional electrochemical-enzymatical measuring methods for l-lactate is mentioned, and reference is made to the clinical importance of l-lactate determination.

     

Stereospecific coordination ofl-hydroxyproline esters with triosmium clusters

The reactions of cluster (-H)Os₃(CO)₁₀(-OH) with ethyl and isopropyl esters ofl-oxyproline were studied. In the presence of Me₃NO intermediate complex (-H)Os₃(CO)₉(-OH)L (L — isopropyl ester ofl-oxyproline) is formed, which slowly converts to the more stable cluster (-H)Os₃(CO)₉ . Cluster complexes containing chelate-bridging heterocycles were also obtained by heating (-H)Os₃(CO)₁₀(-OH) with esters ofl-oxyproline. In both cases, only one of the possible diastereomeric complexes (-H)Os₃(CO)₉ (R = Et, Prⁱ) is formed, which indicates that the reactions are stereospecific. Based on analysis of Dreiding's models, an attempt to determine the absolute configuration of the obtained clusters was made.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2021–2025, October, 1995.     

Chromium (III) trihalide complexes of 4-aminobenzophenone

Summary The following chromium(III) complexes of 4-aminobenzophenone have been prepared and investigated by infrared and electronic spectra and magnetic susceptibility measurements: CrCl₃L, CrCl₃L₂ (pink and brown), CrCl₃L₃, CrCl₃L₆, CrBr₃L₂, CrBr₃L₃, CrBr₃L₄, CrBr₃L₆, CrBr₃L₇ and CrBr₃L₈. The CrBr₃ complexes were each isolated in a yellow and a red form. In the red CrBr₃ and in the yellow CrBr₃L₂ the ligand is bonded through the amine nitrogen. The CrCl₃ complexes are probably molecular complexes.     

Festphasensynthese von 2-l- und 3-d-Pipecolinsäurebradykinin

Zusammenfassung 2-l- und 3-d-Pipecolinsäure-Bradykinin wurden nach der üblichenMerrifield-Technik bzw. nach dem Adsorptions-kupplungs-Verfahren vonEsko undKarlsson dargestellt. Dabei wurde die Eignung von Essigsäureanhydrid, 3-Nitrophthalsäureanhydrid und N-Acetylimidazol für die Blockierung während der Synthese freigebliebener Aminogruppen verglichen. 2-l-Pipecolinsäure-bradykinin war biologisch aktiv.

---

Solid phase synthesis of 2-l- and 3-d-Pipecolic acid-bradykinin

2-l- and 3-d-Pipecolic acid-bradykinin were synthesized using the general procedure ofMerrifield and the adsorption coupling method ofEsko andKarlsson. Acetic anhydride, 3-nitrophthalic anhydride, and N-acetylimidazole were compared with respect to their efficiency as blocking agents for unreacted amino groups. 2-l-pipecolic acid-bradykinin was biologically active.

---

---

Mit 1 Abbildungen

---

Abkürzungen entspr. IUPAC-IUB Commission on Biochemical Nomenclature. J. biol. Chem.241, 527, 2491 (1966);Pipec: Pipecolinsäure,DCCI: N,N-Dicyclohexylcarbodiimid,Boc: tert. Butyloxycarbonyl.     

Unsymmetrically substituted triazacyclohexanes and their chromium complexes

The unsymmetrically N-substituted N,N′-Ar₂-N″-R-1,3,5-triazacyclohexanes 1–4 (Ar = ortho- or para-fluorophenyl, R = n- or iso-propyl) can be obtained in good yields from a one-step condensation reaction with excess amine. Solid state structures of 1–4 resemble closely those of their triaryl-substituted analogues. The condensation reaction to 4 was looked at by detailed NMR investigations and revealed that amine/aniline exchange is occurring in solutions containing free aniline even at ambient conditions setting up an equilibrium between all possible symmetrical and unsymmetrical triazacylcohexanes. Selective crystallisation of 4 from the solution drives the reaction to high yields of 4. Complexes 1–4 react readily with CrCl₃ or CrCl₃(THF)₃ to form the corresponding CrCl₃ complexes. The complexes are insoluble in non-polar solvents and decompose under decomplexation in coordinating solvents.     

Die Herstellung von für die Peptidsynthese geeigneten,optisch aktiven Pipecolinsäurederivaten

Zusammenfassung Zur Darstellung der optisch aktivenl- undd-Formen der den im Pflanzenreich häufig vorkommenden nicht-proteinogenen Aminosäuren zuzuzählenden Pipecolinsäure werden eine neue Spaltungsmethode und in Verbindung damit sechs neue N-Carbobenzoxy-l- und-d-Pipecolinsäurederivate sowie vier aktivierte Ester der N-Carbobenzoxy-l- und-d-Pipecolinsäure, die N-o-Nitro-phenylsulfenyl- und N-t-Butyloxycarbonylabkömmlinge der beiden Antipoden, beschrieben. Diese Derivate werden zur Synthese biologisch aktiver Oligopeptide empfohlen. Es wurden auch die physikalischen Daten der reinenl- undd-Pipecolinsäure ermittelt.

---

Preparation of optically active pipecolic acid derivatives suitable for peptide synthesis

A new method for the resolution of pipecolic acid, a non-proteinogenic amino acid frequently occurring in plants, is described. Six new benzyloxycarbonyl derivatives, four activated esters of benzyloxycarbonyll- andd-pipecolic acid and the o-nitrophenylsulfenyl andt-butoxycarbonyl derivatives ofl- andd-pipecolic acid, useful for the synthesis of biologically active oligopeptides, were prepared. The physical constants of purel- andd-pipecolic acid are reported.

     

Differential pulse polarographic determination of l-lactate with a soluble enzyme preparation

Summary An electrochemical method for the determination of l-lactic acid using the specific reaction of lactate oxidase, has been studied and applied to lactic acid beverage and yoghurt. The technique is reasonably rapid and simple to perform. The calibration curve is linear in the concentration range from 1.0 to 20 mol/l, the reproducibility (R.S.D.) at 10 mol/l l-lactic acid is 1.34% (n=6) and the detection limit is 0.29 mol/l (k=2). The method can possibly be used for monitoring l-lactate or l-lactic acid in food industries and clinical laboratories.     

Thermodynamics of ion association. Part XXIII. Copper,zinc, and cadmium complexes of some dipeptides

Calorimetric and potentiometric studies have been made at 25°C of the formation of zinc and cadmium complexes of diglycine and of the copper complexes of glycylsarcosine, glycineamide, glycylproline, glycyl-l-alanine, -alanylglycine, and glycyl--aminobutyric acid. In addition, a potentiometric investigation has been made of the formation of copperl-alanyl-l-alanine complexes. The data have been used to calculate G, H, and S values for all the equilibria involved and, in the case of copper, these data strongly support a common structure for all the mono complexes at lower pH in which the copper is bound to the terminal—NH₂ and the oxygen of the peptide group. At higher pH, thermodynamic functions have been determined for the dissociation of the peptide hydrogen atom which is labilized by the copper atom.     

Mixed-ligand complexes of nickel(II) involving sulphur-containing ligands and diaminocarboxylic acids

Summary Stability constants for mixed-ligand complexes of the types [NiABH₂], [NiABH] and [NiAB] formed by Ni^II with l-cysteine (cys), d-penicillamine (pen) or l-cysteic acid (cya) as ligand A and dl-2,3-diaminopropionic acid (dapa), dl-2,4-diaminobutyric acid (daba) or dl-ornithine (orn) as ligand B have been determined by the computerbased analysis of pH titration data obtained at 37 °C and I = 0.15 mol dm^–3 (NaClO₄). In the [NiABH] species, for all three secondary ligands (B), when A = pen or cya the labile proton appears to be attached to the terminal amino group of ligand B, whereas when A = cys it is not clear where the proton is located. In all the systems in the [NiABH₂] species, one proton resides with the primary ligand (A) and the other with the secondary ligand (B). In the [NiAB]-type complexes, cys and pen chelate through the amino and thiolato groups, while cya binds in a glycine-like mode and the secondary ligands (B) coordinate in a terdentate manner.Author to whom all correspondence should be directed.     

Determination of dissociation kinetics of 188Re(I)-pharmaceuticals by free-ion selective radiotracer extraction

Due to physical decay properties commonly associated with therapeutic radionuclides, ¹⁸⁸Re (t _1/2 = 16.98 h, E _max = 2.12 MeV) is of high interest for endovascular brachytherapy and endoradiotherapy in general. Rhenium precursors in the low oxidation state +I, such as the organometallic fac-[Re(H₂O)₃(CO)₃]⁺ are promising lead compounds compared to those with oxidation states +III and +V since they can be prepared under mild conditions and do not tend to reoxidize to oxidation state +VII while multidentate ligands can be attached under substitution of coordinated water molecules. This study comprises the application of the Free-Ion Selective Radiotracer Extraction (FISRE) technique in order to determine dissociation rate constants of complexes bearing the [¹⁸⁸Re(CO)₃]⁺-core at tracer levels in vitro with regards to their time-dependent kinetic speciation. As ligands, the tridentate l-histidine as well as the dipeptides l-carnosine (β-alanyl-l-histidine) and glycyl-l-histidine were chosen in order to study the effects of different moieties attached to the primary amine of l-histidine.