Copper(II) complexes with substituted thiosemicarbazones of alpha-ketoglutaric acid: synthesis, X-ray structures, DNA binding studies, and nuclease and biological activity

New alpha-ketoglutaric acid thiosemicarbazone (H(3)ct) derivatives and their copper complexes were synthesized and characterized by analytical and spectroscopic (IR and NMR) methods. For two of the ligands, Me-H(3)ct and Allyl-H(3)ct, and for a complex, [Cu(Me-Hct)(OH(2))](n) x 2nH(2)O, the X-ray structures were also determined. In the latter the copper atom shows a 4 + 1 pyramidal coordination, a water oxygen appears in the apical position, and three of the basal positions are occupied by the SNO tridentate ligand and the fourth by a carboxylic oxygen of an adjacent molecule that gives rise to a polymeric chain. DNA binding constants were determined, and studies of thermal denaturation profiles and nuclease activity were also performed. Tests in vitro on human leukemia cell line U937 were carried out on cell growth inhibition, cell cycle, and apoptosis induction.     

X-ray photoelectron spectra of Ti4+ in TiO2. Evidence of band structure

Satellite structure has been observed at about 3.1, 5.4, 6.4 and 14.5 eV below the main peaks in the X-ray photoelectron spectra of the Ti and O levels of TiO₂. These satellites arise from transitions, accompanying primary photoemission, between predominantly O_2p states of the ligand and various excited states in the conduction band. The energies found fit the transitions calculated by Daude et al. for an electronic band structure calculated by a combined tight-binding and pseudopotential method.     

Theoretical investigations on the solvation process

The conformation energies for monohydrated associates M · H₂O, where M stands for oxirane, aziridine, oxaziridine and cyclopropene, have been obtained by using an electrostatic method, tested in a preceding paper, which relies on SCF molecular potentials calculated exactly. Stable associates have been found in the heterogroup region as well as near the bent bonds (single or double).A discussion is made on the errors in calculating thermodynamic properties for such associates in gas phase by using a priori calculations. As a numerical example the free energy change in the association process is compared for two monohydrated associates of aziridine.

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Zusammenfassung Die Konformationsenergien für Anlagerungsverbindung M · H₂O, wobei M für Oxiran, Aziridin, Oxaziridin und Cyclopropen steht, werden mit einer elektrostatischen Methode berechnet. Dieses Verfahren wurde in einer vorhergehenden Veröffentlichung getestet und beruht auf exakt berechneten SCF-Molekülpotentialen. Stabile Anlagerungsverbindungen wurden für Konformationen gefunden, bei denen das Wassermolekül in der Nähe der Heterogruppe oder der gezogenen Einfach- oder Doppelbindung liegt. Die Fehler bei der Berechnung thermodynamischer Eigenschaften für derartige Anlagerungsverbindungen in der Gasphase werden abgeschätzt. Als ein numerisches Beispiel wird die Differenz der freien Energie bei der Anlagerung für zwei Anlagerungsverbindungen von Aziridin und Molekül Wasser verglichen.

     

Acetobacter cellulosic biofilms search for new modulators of cellulogenesis and native membrane treatments

Since natural substances like pseudoxanthins exert a positive effect on the cellulogenic ability ofAcetobacter xylinum when producing cellulosic pellicles suitable for skin burn therapy, new defined and complex modulators were sought. Ca²⁺ and Mg²⁺ (4 mM) were strongly stimulatory. Na⁺ had no effect and K⁺ was inhibitory. Ammonium dihydrogen phosphate (0.12 g/L) ensured the same nitrogen supply as the same concentration of yeast extract as measured by cellomembrane dry wt./yield albeit higher yeast extract supplies produced thicker membranes. Corn steep liquor (CSL) was also progressively beneficial from 0.125 to 0.5 mL/L, and this yield could be further improved by the combination of CSL with a tea infusion (source of caffeine). Uridine (precursor for UDP-Glc, sugar donor in cellulose biosynthesis), guanine, guanosine, and its butirylated derivatives (precursors for the positive modulator of cellulose synthetase, di-cGMP) resulted in only moderate stimulation. Sodium phytate and betaine were also slightly stimulatory. The fibrilar product from a newAcetobacter isolate (Ax-M) was characterized as cellulose by comparison with the solid-state¹³C-NMR of algal cellulose. Its X-ray diffractogram was a confirmatory analysis. After incorporation of tamarind xyloglucan to previously air-dried cellulosic pellicles, diffractometry displayed only slight differences. Mercerized (5M NaOH) fresh cellulosic biofilms underwent drastic size reduction (3.5-fold), turning compact nut still flexible if maintained wet.     

Homoleptic cobalt and copper phenolate A2[M(OAr)4] compounds: the effect of phenoxide fluorination

Two series of homoleptic phenolate complexes with fluorinated aryloxide ligands A2[M(OAr)4] with M=Co2+ or Cu2+, OAr-=(OC6F5)- (OArF) or [3,5-OC6H3(CF3)2]- (OAr'), A+=K (18-crown-6)+, Tl+, Ph4P+, Et3HN+, or Me4N+ have been synthesized. Two related complexes with nonfluorinated phenoxide ligands have been synthesized and studied in comparison to the fluorinated aryloxides demonstrating the dramatic structural changes effected by modification of OPh to OAr(F). The compounds [K(18-crown-6)]2[Cu(OArF)4], 1a; [K(18-crown-6)]2[Cu(OAr')4], 1b; [Tl2Cu(OArF)4], 2a; [Tl2Cu(OAr')4], 2b; (Ph4P)2[Cu(OArF)4], 3; (nBu4N)2[Cu(OArF)4], 4; (HEt3N)2[Cu(OArF)4], 5; [K(18-crown-6)]2[Cu2(mu2-OC6H5)2(OC6H5)4], 6; [K(18-crown-6)]2[Co(OArF)4], 7a; [(18-crown-6)]2[Co(OAr')4], 7b; [Tl2Co(OArF)4], 8a; [Tl2Co(OAr')4], 8b; (Me4N)2[Co(OArF)4], 9; [Cp2Co]2[Co(OAr')4], 10; and [(18-crown-6)])[Co2(mu2-OC6H5)2(OC6H5)4], 11, have been characterized with UV-vis and multinuclear NMR spectroscopy and solution magnetic moment studies. Cyclic voltammetry was used to study 1a, 1b, 7a, and 7b. X-ray crystallography was used to characterize 1b, 3, 4, 5, 6, 7a, 7b, 10, and 11. The related [MX4]2- compound (Ph4P)2[Co(OArF)2Cl2], 12, has also been synthesized and characterized spectroscopically, as well as with conductivity and single-crystal X-ray diffraction. Use of fluorinated aryloxides permits synthesis and isolation of the mononuclear, homoleptic phenolate anions in good yield without oligomerized side products. The reaction conditions that result in homoleptic 1a and 7a with OArF upon changing the ligand to OPh result in mu2-OPh bridging phenoxides and the dimeric complexes 6 and 11. The [M(OArF)4]2- and [M(OAr')4]2- anions in 1a, 1b, 3, 4, 5, 7a, 7b, 9, and 10 demonstrate that stable, isolable homoleptic phenolate anions do not need to be coordinatively or sterically saturated and can be achieved by increasing the electronegativity of the ligand.     

Electronic structure of friedel crafts catalysts BF3+HF

SCF MO LCAO calculations using two different gaussian basis sets have been performed for the species HF, F^?, BF₃, BF ₄ ^? and HBF₄ with geometry optimization. Differences in electrophilicity and proton donating capability of HF due to the formation of the adduct with BF₃ are evidenced and discussed.     

Supramolecular Cationic Tetraruthenated Porphyrin Induces Single-Strand Breaks and 8-Oxo-7,8-dihydro-2'-deoxyguanosine Formation in DNA in the Presence of Light

Abstract— The aim of this investigation is the evaluation of DNA interaction of with tetraruthenated porphyrin (TRP) and of DNA damage in the presence of light. Direct-fluorescence and electronic absorption measurements after incubation of DNA with TRP indicate strong binding between pBR322 DNA or calf thymus DNA with the modified porphyrin. Exposure of pBR322 DNA to TRP (up to 3 μ M ) and light leads to single-strand break formation as determined by the conversion of the supercoiled form (form I) of the plasmid into the nicked circular form (form II). Oxidative DNA base damage was evaluated by the detection of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) after irradiation of calf thymus DNA in the presence of the TRP. The data demonstrated a dose and time dependence with each type of DNA damage. These data indicate (1) a specificity of the binding mode and (2) type I and II photoinduced mechanisms leading to strand scission activity and 8-oxodGuo formation. Accordingly, singlet molecular oxygen formation, after TRP excitation, was confirmed by near-infrared emission. From these investigations a potential application of TRP in photodynamic therapy is proposed.     

Synthesis and pharmacological evaluation of new progesterone esters as 5alpha-reductase inhibitors

In this study we report the synthesis and pharmacological evaluation of four new progesterone derivatives; 17alpha-hydroxy-16beta-methylpregna-4,6-diene-3,20-dione 12, 17alpha-cyclopropylcarbonyloxy-16beta-methylpregna-4,6-diene-3,20-dione 13, 17alpha-cyclobutylcarbonyloxy-16beta-methylpregna-4,6-diene-3,20-dione 14, 17alpha-acetoxy-16beta-methylpregna-4,6-diene-3,20-dione 15 and the pregnatriene compound 17alpha-cyclobutylcarbonyloxy-16beta-methylpregna-1,4,6-triene-3,20-dione 16. The pharmacological effect of these compounds was determined in vivo as well as in vitro. The evaluation in vivo was carried out on gonadectomized male hamsters that were injected subcutaneously daily with testosterone (T) and/or finasteride, or with the novel compounds. At the end of the treatments the animals were sacrificed and the prostates were weighed. It was observed that when testosterone (T) and finasteride or compounds 12-16 were injected together, the weight of the prostate decreased significantly as compared to that of the testosterone-treated animals. The 5alpha-reductase inhibitory activity was evaluated in vitro using human prostate homogenates. These experiments showed the following IC50 values: compound 12 (alcohol at C-17) 1.2 x 10(-6) M, 13 (cyclopropyl substituent at C-17) 7.9 x 10(-10) M, 14 (cyclobutyl substituent) 3.2 x 10(-8) M, 15 (acetoxy substituent) 6.3 x 10(-11) M and 16 (cyclobutyl substituent) 3.9 x 10(-6) M. It is evident from these data that when the size of the substituent at C-17 is decreased, the 5alpha-reductase inhibitory activity increases. Apparently, in this biological model, the 5alpha-reductase inhibitory activity depends upon the steric effect of the substituent at C-17. However, the free alcohol 12 showed much lower 5alpha-reductase inhibitory activity.     

The Orienteering Problem with Time Windows

The orienteering problem with time windows, denoted by OPTW, belongs to a class of routeing and scheduling problems that arise in physical distribution. It may be modelled as a problem on a graph. It considers a set of nodes (customers), each with an associated profit and service duration (time window), and a set of arcs, each with an associated travel time. The objective of the problem is to construct an acyclic path beginning at a specified origin and ending at a specified destination that maximizes the total profit while observing time window constraints on all nodes and not exceeding a designated time limit. The problem is classified as NP-hard and, thus, an exact algorithm that executes in reasonable computational time is unlikely to exist. Since the problem is highly-constrained, we were able to develop a heuristic (referred to as the ‘tree’ heuristic) based upon an exhaustive search of the feasible solution space. The tree heuristic systematically generates a list of feasible paths and then selects the most profitable path from the list. In comparison with an insertion heuristic, the tree heuristic was found to produce improved values of total profit for heavily-constrained, modest-sized problems with reasonable computational effort.