Catalytic Properties of Two Complexes of chromium(III) and cobalt(II) with Nitrilotriacetate, Dipicolinate, and 4-Acetylpyridine.

In this paper, a synthesis of two innovative coordination compounds, based on chromium(III) and cobalt(II) ions with N,O-donor ligands (nitrilotriacetate, dipicolinate) and 4-acetylpyridine, is reported. The obtained metal-organic compounds were structurally characterized using the single-crystal X-ray diffraction (XRD) method. The well-defined chromium(III) and cobalt(II) complexes were used as precatalysts in the oligomerization reaction of 2-chloro-2-propen-1-ol and 2-propen-1-ol with methylaluminoxane (MMAO) as an activator. The products of the oligomerization reaction were subjected to full physicochemical characteristics, i.e., time-of-flight mass spectrometry (MALDI-TOF-MS), TGA, and differential scanning calorimetry (DSC) methods. The catalytic activity of the precatalysts in both reactions was calculated and compared with other catalysts known in the literature.

Bis(5-chloroquinolin-8-olato)-bis(pyridine)-cobalt(II) as new catalytic material.

Nowadays, studies are carried out on the design and synthesis of new catalysts for olefin oligomerization and polymerization, which would contain non-toxic metals and at the same time show high catalytic activities. Complex compounds of transition metal ions such as Fe(II), Cr(III) and Zr(II) containing pyridine or quinoline as ligands show at least moderate catalytic activity in ethylene and propylene polymerizations. To investigate the catalytic activity of the complex containing pyridine ligands and quinoline derivatives, here we have synthesized the crystals of new bis(5-chloroquinolin-8-olato)-bis(pyridine)-cobalt(II) solvate. The synthesized cobalt(II) complex compound was tested in reactions of 2-chloro-2-propen-1-ol and norbornene oligomerizations. Our studies showed that bis(5-chloroquinolin-8-olato)-bis(pyridine)-cobalt(II) after activation by MMAO-12 catalyzes the formation of oligomers in nitrogen atmosphere, under atmospheric pressure and at room temperature. Bis(5-chloroquinolin-8-olato)-bis(pyridine)-cobalt(II) possesses moderate catalytic activity in the formation of norbornene oligomers process and low catalytic activity in 2-chloro-2-propen-1-ol oligomerization.

Cat-CrNP as new material with catalytic properties for 2-chloro-2-propen-1-ol and ethylene oligomerizations.

The contemporary search for new catalysts for olefin oligomerization and polymerization is based on the study of coordinating compounds and/or organometallic compounds as post-metallocene catalysts. However known catalysts are suffered by many flaws, among others unsatisfactory activity, requirement of high pressure or instability at high temperatures. In this paper, we present a new catalyst i.e. the crystalline complex compound possesing high catalytic activity in the oligomerization of olefins, such as 2-chloro-2-propen-1-ol and ethylene under very mild conditions (room temperature, 0.12 bar for ethylene oligomerization, atmospheric pressure for 2-chloro-2-propen-1-ol oligomerization). New material-Cat-CrNP ([nitrilotriacetato-1,10-phenanthroline]chromium(III) tetrahydrate) has been obtained as crystalline form of the nitrilotriacetate complex compound of chromium(III) with 1,10-phenanthroline and characterized in terms of its crystal structure by the XRD method and by multi-analytical investigations towards its physicochemical propeties The yield of catalytic oligomerization over Cat-CrNP reached to 213.92 g · mmol-1 · h-1· bar-1 and 3232 g · mmol-1 · h-1 · bar-1 for the 2-chloro-2-propen-1-ol and ethylene, respectively. Furthemore, the synthesis of Cat-CrNP is cheap, easy to perform and solvents used during preparation are environmentally friendly.

New chromium(III)-based catalysts for ethylene oligomerization.

The report focuses on the new precatalysts for ethylene oligomerization. The five chromium(III) complex compounds containing the following ligands: dipicolinate anion, oxalate anion, 5-aminopyridine-2-carboxylate anion, 2,2'-bipyridine and 4,4'-dimethoxy-2,2'-bipyridine have been examined towards catalytic activity for ethylene oligomerization. The chromium(III) complexes have been activated by modified methylaluminoxane. The obtained oligomers have been investigated by MALDI-TOF-MS, thermal analysis and infrared spectroscopy. The results revealed that the examined chromium(III) complexes are highly active catalysts for ethylene oligomerization. The values of catalytic activities of the examined complexes are in the range 1860 - 3798 g∙mmol-1∙h-1∙bar-1.

Application of Coordination Compounds with Transition Metal Ions in the Chemical Industry-A Review.

This publication presents the new trends and opportunities for further development of coordination compounds used in the chemical industry. The review describes the influence of various physicochemical factors regarding the coordination relationship (for example, steric hindrance, electron density, complex geometry, ligand), which condition technological processes. Coordination compounds are catalysts in technological processes used during organic synthesis, for example: Oxidation reactions, hydroformylation process, hydrogenation reaction, hydrocyanation process. In this article, we pointed out the possibilities of using complex compounds in catalysis, and we noticed what further research should be undertaken for this purpose.

Inhibitors of human immunodeficiency virus type 1 (HIV-1) attachment. 12. Structure-activity relationships associated with 4-fluoro-6-azaindole derivatives leading to the identification of 1-(4-benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1h-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-585248).

A series of highly potent HIV-1 attachment inhibitors with 4-fluoro-6-azaindole core heterocycles that target the viral envelope protein gp120 has been prepared. Substitution in the 7-position of the azaindole core with amides (12a,b), C-linked heterocycles (12c-l), and N-linked heterocycles (12m-u) provided compounds with subnanomolar potency in a pseudotype infectivity assay and good pharmacokinetic profiles in vivo. A predictive model was developed from the initial SAR in which the potency of the analogues correlated with the ability of the substituent in the 7-position of the azaindole to adopt a coplanar conformation by either forming internal hydrogen bonds or avoiding repulsive substitution patterns. 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-585248, 12m) exhibited much improved in vitro potency and pharmacokinetic properties than the previous clinical candidate BMS-488043 (1). The predicted low clearance in humans, modest protein binding, and good potency in the presence of 40% human serum for 12m led to its selection for human clinical studies.

Utilization of in vitro Caco-2 permeability and liver microsomal half-life screens in discovering BMS-488043, a novel HIV-1 attachment inhibitor with improved pharmacokinetic properties.

Optimizing pharmacokinetic properties to improve oral exposure is a common theme in modern drug discovery. In the present work, in vitro Caco-2 permeability and microsomal half-life screens were utilized in an effort to guide the structure-activity relationship in order to improve the pharmacokinetic properties of novel HIV-1 attachment inhibitors. The relevance of the in vitro screens to in vivo pharmacokinetic properties was first demonstrated with a number of program compounds at the early stage of lead optimization. The Caco-2 permeability, tested at 200 microM, was quantitatively predictive of in vivo oral absorption, with complete absorption occurring at a Caco-2 permeability of 100 nm/s or higher. The liver microsomal half-life screen, conducted at 1 microM substrate concentration, can readily differentiate low-, intermediate-, and high-clearance compounds in rats, with a nearly 1:1 correlation in 12 out of 13 program compounds tested. Among the >100 compounds evaluated, BMS-488043 emerged as a lead, exhibiting a Caco-2 permeability of 178 nm/s and a microsomal half-life predictive of a low clearance (4 mL/min/kg) in humans. These in vitro characteristics translated well to the in vivo setting. The oral bioavailability of BMS-488043 in rats, dogs, and monkeys was 90%, 57%, and 60%, respectively. The clearance was low in all three species tested, with a terminal half-life ranging from 2.4 to 4.7 h. Furthermore, the oral exposure of BMS-488043 was significantly improved (6- to 12-fold in rats and monkeys) compared to the prototype compound BMS-378806 that had a suboptimal Caco-2 permeability (51 nm/s) and microsomal half-life. More importantly, the improvements in preclinical pharmacokinetics translated well to humans, leading to a >15-fold increase in the human oral exposure of BMS-488043 than BMS-378806 and enabling a clinical proof-of-concept for this novel class of anti-HIV agents. The current studies demonstrated the valuable role of in vitro ADME screens in improving oral pharmacokinetics at the lead optimization stage.

Unusual 4-hydroxybenzaldehyde synthase activity from tissue cultures of the vanilla orchid Vanilla planifolia.

Tissue cultures of the vanilla orchid, Vanilla planifolia, produce the flavor compound vanillin (4-hydroxy-3-methoxybenzaldehyde) and vanillin precursors such as 4-hydroxybenzaldehyde. A constitutively expressed enzyme activity catalyzing chain shortening of a hydroxycinnamic acid, believed to be the first reaction specific for formation of vanilla flavor compounds, was identified in these cultures. The enzyme converts 4-coumaric acid non-oxidatively to 4-hydroxybenzaldehyde in the presence of a thiol reagent but with no co-factor requirement. Several forms of this 4-hydroxybenzaldehyde synthase (4HBS) were resolved and partially purified by a combination of hydrophobic interaction, ion exchange and gel filtration chromatography. These forms appear to be interconvertible. The unusual properties of the 4HBS, and its appearance in different protein fractions, raise questions as to its physiological role in vanillin biosynthesis in vivo.