The Synthesis of Novel Methotrexate-like Compounds

Summary. Methotrexate (MTX) is a folate antagonist used in treatment of several chronic inflammatory and neoplastic conditions. In this study, new MTX-like compounds that may-be potential anticancer agents were synthesized and their structures were determined by IR, UV, GC-MS, ¹H NMR, and ¹³C NMR spectra. Also, in this study, a series structurally related to MTX or folate analogous compounds were evaluated whether they have inhibitory properties on the dihydrofolate reductase activity (DHFR).     

Co(II), Ni(II) and Cu(II) complexes of 1,4-di-(1-hydroxyimino-2-phenyl-2-oxo-ethylamino)benzene

The ligand has been prepared from ω-chloroisonitrosoacetophenone and 1,4-phenylenediamine in the presence of NaHCO₃. The ligand have a C=O group and an –NH–R group adjacent to the oxime group. The Ni(II), Cu(II) and Co(II) complexes of the synthesized ligand were prepared and their structures were identified using FTIR, UV-Vis spectral data, elemental analysis, thermal analysis and magnetic moment measurements. The metal-ligand ratios were found to be 3:2. The ligands were found to coordinate to the metal ions via the oxime nitrogen, oxime oxygen, one of the carbonyl group and amide nitrogen atoms. Thermal analyses data reveals that the water in the complexes was found to be non-coordinated to the metal ions. In the trinuclear structures, the metals have the tetrahedral environments.     

Synthesis of novel unsymmetrical phthalocyanines substituted with crown ether and nitro groups

This work reports on the synthesis of new unsymmetrically substituted phthalocyanines (M = Zn, Cu, Co, Ni) bearing three benzo-15-crown-5 units through oxy bridges and a nitro group. Phthalocyanines were prepared by a statistical condensation of 4-nitro phthalonitrile and 1-{[(benzo-15-crown-5)-4′-yl]oxy}phthalonitrile in the presence of anhydrous metal salts. All the target unsymmetrical phthalocyanines were separated by column chromatography and characterized elemental analyses, ¹H NMR, IR, mass and UV–Vis spectral data. Electrochemical behaviors of Cu (II) phthalocyanine by cyclic voltammetry and differential pulse voltammetry techniques gave two common phthalocyanine ring reductions and one ring oxidation processes. Peak-to-peak separation of the processes II and III (388 mV) and the measure of gap (1.672 V) between the HOMO and LUMO for the complex, fits a phthalocyanine with electrochemically inactive metal center.     

Alcohol-soluble functional vic-dioxime bearing alcoholhexylsulfanyl moieties: preparation, spectroscopy and electrochemistry

A new alcohol soluble functionalized vic-dioxime, bis-[(1-hydroxyhexyl)-(8,9-hydroxyimino)-7,10-dithiahexacosane (LH₂), and its alcohol-soluble mono and dinuclear complexes (Ni^II, Cu^II, Co^II, Mn^II, Pd^II and UO ₂ ^II ) have been prepared from 6-mercapto-1-hexanol and (E,E)-dichloroglyoxime under high dilution basic conditions. Reactive polyalcohol moieties appended at the periphery of the oxime containing two different heteroatoms (S-, O-), serve as a weak exocyclic binding sites for Pd^II and Ag^I metal ions and also provide solubility for the vic-dioxime complexes in low molecular-weight alcohols. Both mono-nuclear (LH)₂M and homodinuclear (LH)₂(UO₂)₂(OH)₂ and heterotrinuclear (LH)₂MM ₂ ^′ Xn, where M = Co^II M′ = Pd^II, X = Cl⁻, n = 4 and Ag^I X = NO ₃ ⁻ , n = 2) complexes have been obtained with a 1:2, 2:2, 3:2 metal/ligand ratio, respectively. Electronic spectra of the modified vic-dioximes exhibit monitorable changes in UV. All mono and dinuclear-complexes are soluble in common organic solvents. The elemental analysis, ¹H-n.m.r, i.r., u.v–vis, and f.a.b.–m.s data and by cyclic and differential pulse voltammetry measurements are presented.     

Dissociation constants of some Schiff bases and stability constants of their copper,cobalt, nickel and zinc complexes

The stoichiometry and stability constant of metal complexes with 4-(3-methoxy-salicylideneamino)-5-hydroxynaphthalene-2,7-disulfonic acid monosodium salt (H₂L) and 4-(3-methoxysalicylideneamino)-5-hydroxy-6-(2,5-dichlorophenylazo)-2,7-naphthalene disulfonic acid monosodium salt (H₂L¹) were studied by potentiometric titration. The stability constants of H₂L and H₂L¹ Schiff bases have been investigated by potentiometric titration and u.v.–vis spectroscopy in aqueous media. The dissociation constants of the ligand and the stability constants of the metal complexes were calculated pH-metrically at 25 °C and 0.1 m KCl ionic strength. The dissociation constants for H₂L were obtained as 3.007, 7.620 and 9.564 and for H₂L¹, 4.000, 6.525, 9.473 and 10.423, respectively. The complexes were found to have the formulae [M(L)₂] for M = Co(II), Ni(II), Zn(II) and Cu(II). The stability of the complexes follows the sequence: Zn(II) < Co(II) < Cu(II) < Ni(II). The high stability of H₂L¹ towards Cu(II) and Ni(II) over the other ions is remarkable, in particular over Cu(II), and may be of technological interest. Concentration distribution diagram of various species formed in solution was evaluated for ligands and complexes. The formation of the hydrogen bonds may cause this increased stability of ligands. The pH-metric data were used to find the stoichiometry, deprotonation and stability constants via the SUPERQUAD computer program.     

Synthesis and Characterization of Mononuclear Cobalt(II), Nickel(II), Copper(II), Zinc(II), Cadmium(II) and Dinuclear Uranyl(VI) Complexes with N,N-bis(2-{[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]amino}butyl) N′,N′-dihydroxyethanediimidamide

In this study, the new vic-dioxime ligand (LH₂) and its complexes with Co^II, Ni^II, Cu^II, Zn^II, Cd^II and UO₂^VI are described. The structures of these complexes were characterized by elemental analyses, i.r., ¹H- and ¹³C-n.m.r. spectra, u.v.–vis. spectroscopy, magnetic susceptibility measurements, conductivity measurements and thermogravimetric analyses (t.g.a.).     

Synthesis of a bipyridine-derived achiral thiourea trifluoromethanesulfonic acid salt and its application as an additive in organocatalytic asymmetric reactions

The host–guest complex of a proline–thiourea bipyridine trifluoromethanesulfonic acid salt can catalyze organocatalytic asymmetric reactions such as aldol, Michael, and Mannich in polar protic medium with high stereoselectivities. The privileged bipyridine backbone and the thiourea motif are essential to the activity and enantioselectivity through hydrogen bonding interactions.     

Study of asymmetric aldol and Mannich reactions catalyzed by proline–thiourea host–guest complexes in nonpolar solvents

A proline–thiourea host–guest complex has been described as a good catalyst for asymmetric reactions such as aldol and Mannich reactions. High stereoselectivities were obtained under optimal conditions. Thiourea was observed to have an important effect on the reactivity and selectivity, even in an unconventional nonpolar reaction medium and without the need to utilize low temperatures. This proline–thiourea host–guest system has the ability to participate in a hydrogen bonding network.     

Fluorescence Interaction and Determination of Sulfathiazole with Trypsin

The mechanism of interaction of trypsin with the sulfathiazole was studied through using fluorescence quenching and UV-visible absorption spectra at pH 7.4. The Stern-Volmer quenching constants, binding constants, number of binding sites and the corresponding thermodynamic parameters ΔH^o, ΔS^o and ΔG^o were calculated at different temperatures. The effect of common metal ions on the constants was also discussed. The results suggest that sulfathiazole can interact strongly trypsin and that there is the formation of trypsin-sulfathiazole complex and the interaction can be explained on the basis of hydrogen bonds and van der Waals forces. The binding distance (r) between the donor (trypsin) and acceptor (sulfathiazole) was 3.52 nm based on the Förster’s non-radiative energy transfer theory. The detection and quantification limits of sulfathiazole were calculated as 2.52 and 8.40 μM in the presence of trypsin, respectively. The relative standard deviation (RSD) was 4.086 % for determinations (n?=?7) of a sulfathiazole solution with the concentration of 7.54 μM.