Coordination diversity of N-phosphoryl-N′-phenylthiourea (LH) towards Co, Ni and Pd cations: Crystal structure of ML2-N,S and ML2-O,S chelates

Thiourea, PhNHC(S)NHP(O)(OPrⁱ)₂ (LH) chelates of Co^II, Ni^II, and Pd^II ions have been obtained and investigated by single-crystal X-ray diffraction, UV, IR, NMR spectroscopy, and EI mass-spectrometry. The unusual 1,3-N,S-coordination via sulfur and NP(O) nitrogen atoms has been found in the trans-square-planar NiL₂ and PdL₂ complexes, whereas the 1,5-O,S-coordination is realized in the tetrahedral CoL₂ complex. DFT calculations have revealed significant stabilization of the 1,3-N,S-structures due to stronger crystal field and the NH-OP hydrogen bonds.     

Cu(II) Schiff-base complex with [N3O] binding site and a pendant S-methylisothiosemicarbazide arm

A neutral four-coordinate Cu^IIN₃O complex with Shiff base ligand, product of template assembling of two S-methylisothiosemicarbazide units with benzoylacetone and nitromalondialdehyde, was synthesized by two steps procedure via Cu^IIN₂O₂ chelate precursor and was fully characterized by elemental analysis, IR, UV-Vis, ESR spectra and magnetochemistry. X-ray analysis confirms its structural assignment. The assembling ligand assumes an acyclic structure of ‘4+1’ type where a non-bonding interaction between the metal and the amino group of one S-methylisothiosemicarbazide unit takes place.     

Stereospecific ligands and their complexes. V. Synthesis, characterization and antimicrobial activity of palladium(II) complexes with some alkyl esters of (S,S)-ethylenediamine-N,N′-di-2-propanoic acid

Three new ligands and their palladium(II) complexes of general formula [PdCl₂(R₂-S,S-eddp)] (R = n-propyl, n-butyl and n-pentyl) have been synthesized and characterized by microanalysis, infrared and ¹H and ¹³C NMR spectroscopy. Antimicrobial activity of these ligands and complexes was tested by microdilution method and both minimal inhibitory and microbicidal concentration were determined. These tested complexes demonstrated the significant antifungal activity against pathogenic fungi Aspergillus flavus and Aspergillus fumigatus. On the other hand, these complexes demonstrated moderate antibacterial activity.     

Reactions of the fac-[Re(CO)3] and [ReO] moieties with substituted benzothiazoles

The reaction of 2-(2-aminophenyl)benzothiazole (Habt) with [Re(CO)₅Br] led to the isolation of the rhenium(I) complex fac-[Re(Habt)(CO)₃Br] (1). With trans-[ReOCl₃(PPh₃)₂], the ligand Habt decomposed to form the oxofree rhenium(V) complex [Re(itp)₂Cl(PPh₃)] (2) (itp = 2-amidophenylthiolate). From the reaction of trans-[ReOBr₃(PPh₃)₂] with 2-(2-hydroxyphenyl)benzothiazole (Hhpd) the complex [Re^VOBr₂(hpd)(PPh₃)] (3) was obtained. Complexes 1-3 are stable and lipophilic. ¹H NMR and infrared assignments, as well as the X-ray crystal structures, of the complexes are reported.     

Geometrical isomers of bis(benzimidazol-2-ylethyl)sulfide)cobalt(II) diperchlorates: synthesis, structure, spectra and redox behavior of pink-[Co(bbes)2](ClO4)2 and blue-[Co(bbes)2](ClO4)2

1:1 and 1:2 cobalt complexes of bis(benzimidazol-2-ylmethyl)amine (bbma) bis(benzimidazol-2-ylmethyl)sulfide (bbms), bis(benzimidazol-2-ylethyl)sulfide (bbes) and diethylenetriamine (dien) were prepared and their spectral and redox behavior studied. Two geometrical isomers pink-[Co(bbes)₂]²⁺ and blue-[Co(bbes)₂]²⁺ were obtained when the complexes were prepared by using with bbes and they were separated manually and recrystallized. The octahedral structure of pink-[Co(bbes)₂]²⁺ was resolved by X-ray analysis. The electronic spectra show the presence of two geometrical isomers for Co(bbes)₂²⁺ in the solid state; for example, the spectral bands of pink-[Co(bbes)₂]²⁺ differs markedly with those of blue-[Co(bbes)₂]²⁺. This is consistent with the results obtained from magnetic measurements (5.10 BM for pink-Co(bbes)₂²⁺ and 4.72 BM for blue-[Co(bbes)₂]²⁺). Further, the behavior of the ligands (bbma, bbms, bbes) at different pH conditions was determined on the basis of ¹³C NMR studies. The redox potentials [Co(II)/Co(I)] of the complexes follow the trend [Co(bbma)₂]²⁺ < [Co(bbms)₂]²⁺ ≈ [Co(bbes)₂]²⁺ which demonstrates the stabilization of the Co(II) ion is more by both weak σ-donor and weak π-acceptor ligands rather than by σ-donor ligand.     

Repair efficiency of (5′S)-8,5′-cyclo-2′-deoxyguanosine and (5′S)-8,5′-cyclo-2′-deoxyadenosine depends on the complementary base

5′-R and 5′-S diastereoisomers of 8,5′-cyclo-2′-deoxyadenosine (cdA) and 8,5′-cyclo-2′-deoxyguanosine (cdG) containing a base-sugar covalent bond are formed by hydroxyl radicals. R-cdA and S-cdA are repaired by nucleotide excision repair (NER) in mammalian cellular extracts. Here, we have examined seven purified base excision repair enzymes for their ability to repair S-cdG or S-cdA. We could not detect either excision or binding of these enzymes on duplex oligonucleotide substrates containing these lesions. However, both lesions were repaired by HeLa cell extracts. Dual incisions by human NER on a 136-mer duplex generated 24–32 bp fragments. The time course of dual incisions were measured in comparison to cis-anti-B[a]P-N²-dG, an excellent substrate for human NER, which showed that cis-anti-B[a]P-N²-dG was repaired more efficiently than S-cdG, which, in turn, was repaired more efficiently than S-cdA. When NER efficiency of S-cdG with different complementary bases was investigated, the wobble pair S-cdG·dT was excised more efficiently than the S-cdG·dC pair that maintains nearly normal Watson-Crick base pairing. But S-cdG·dA mispair with no hydrogen bonds was excised less efficiently than the S-cdG·dC pair. Similar pattern was noted for S-cdA. The S-cdA·dC mispair was excised much more efficiently than the S-cdA·dT pair, whereas the S-cdA·dA pair was excised less efficiently. This result adds to complexity of human NER, which discriminates the damaged base pairs on the basis of multiple criteria.     

Synthetic, EPR spectroscopic, magnetic and X-ray crystallographic structural studies on copper(II) complexes of the tridentate N2S donor ligand formed from 6-methyl-2-formylpyridine and S-methyldithiocarbazate (Hmpsme)

New copper(II) complexes of general empirical formula, Cu(mpsme)X · xCH₃COCH₃ (mpsme = anionic form of the 6-methyl-2-formylpyridine Schiff base of S-methyldithiocarbazate; X = Cl, N₃, NCS, NO₃; x = 0, 0.5) have been synthesized and characterized by IR, electronic, EPR and susceptibility measurements. Room temperature μ_eff values for the complexes are in the range 1.75-2.1 μ_B typical of uncoupled or weakly coupled Cu(II) centres. The EPR spectra of the [Cu(mpsme)X] (X = Cl, N₃, NO₃, NCS) complexes reveal a tetragonally distorted coordination sphere around the mononuclear Cu(II) centre. We have exploited second derivative EPR spectra in conjunction with Fourier filtering (sine bell and Hamming functions) to extract all of the nitrogen hyperfine coupling matrices. While the X-ray crystallography of [Cu(mpsme)NCS] reveals a linear polymer in which the thiocyanate anion bridges the two copper(II) ions, the EPR spectra in solution are typical of a magnetically isolated monomeric Cu(II) centres indicating dissociation of the polymeric chain in solution. The structures of the free ligand, Hmpsme and the {[Cu(mpsme)NO₃] · 0.5CH₃COCH₃}₂ and [Cu(mpsme)NCS]_n complexes have been determined by X-ray diffraction. The {[Cu(mpsme)NO₃] 0.5CH₃COCH₃}₂ complex is a centrosymmetric dimer in which each copper atom adopts a five-coordinate distorted square-pyramidal geometry with an N₂OS₂ coordination environment, the Schiff base coordinating as a uninegatively charged tridentate ligand chelating through the pyridine and azomethine nitrogen atoms and the thiolate, an oxygen atom of a unidentate nitrato ligand and a bridging sulfur atom from the second ligand completing the coordination sphere. The [Cu(mpsme)(NCS)]_n complex has a novel staircase-like one dimensional polymeric structure in which the NCS⁻ ligands bridge two adjacent copper(II) ions asymmetrically in an end-to-end fashion providing its nitrogen atom to one copper and the sulfur atom to the other.     

Distant Neighbor Base Sequence Context Effects in Human Nucleotide Excision Repair of a Benzo[a]pyrene-derived DNA Lesion

The effects of non-nearest base sequences, beyond the nucleotides flanking a DNA lesion on either side, on nucleotide excision repair (NER) in extracts from human cells were investigated. We constructed two duplexes containing the same minor groove-aligned 10S (+)-trans-anti-B[a]P-N²-dG (G?) DNA adduct, derived from the environmental carcinogen benzo[a]pyrene (B[a]P): 5′-C-C-A-T-C-G?-C-T-A-C-C-3′ (CG?C-I), and 5′-C-A-C3-A4-C5-G?-C-A-C-A-C-3′ (CG?C-II). We used polyacrylamide gel electrophoresis to compare the extent of DNA bending, and molecular dynamics simulations to analyze the structural characteristics of these two DNA duplexes. The NER efficiencies are 1.6(± 0.2)-fold greater in the case of the CG?C-II than the CG?C-I sequence context in 135-mer duplexes. Gel electrophoresis and self-ligation circularization experiments revealed that the CG?C-II duplex is more bent than the CG?C-I duplex, while molecular dynamics simulations showed that the unique -C3-A4-C5- segment in the CG?C-II duplex plays a key role. The presence of a minor groove-positioned guanine amino group, the Watson-Crick partner to C3, acts as a wedge; facilitated by a highly deformable local -C3-A4- base step, this amino group allows the B[a]P ring system to produce a more enlarged minor groove in CG?C-II than in CG?C-I, as well as a local untwisting and enlarged and flexible Roll only in the CG?C-II sequence. These structural properties fit well with our earlier findings that in the case of the family of minor groove 10S (+)-trans-anti-B[a]P-N²-dG lesions, flexible bends and enlarged minor groove widths constitute NER recognition signals, and extend our understanding of sequence context effects on NER to the neighbors that are distant to the lesion.     

Magnetic, spectroscopic and X-ray crystallographic structural studies on copper(II) complexes of tridentate NNS Schiff base ligands formed from 2-acetylpyrazine and S-methyl- and S-benzyldithiocarbazates

New copper(II) complexes of general empirical formula, [Cu(NNS)X] (NNS = anionic forms of the 2-acetylpyrazine Schiff bases of S-methyl- and S-benzyldithiocarbazate, Hapsme and Hapsbz) and X = Cl⁻, Br⁻, NCS⁻ and NO₃⁻ have been synthesized and characterized. X-ray crystal structures of the free ligand, Hapsbz and the complexes, [Cu(apsbz)(NO₃)]_∞, [Cu(apsme)(NCS)]₂ and [Cu(apsme)Cl]₂ have been determined. In the solid state, the Schiff base, Hapsbz remains in its thione tautomeric form with the thione sulfur atom trans to the azomethine nitrogen atom. X-ray diffraction shows that the [Cu(apsbz)(NO₃)]_∞ complex is a novel coordination polymer in which one of the nitrogen atoms of the pyrazine ring bridges two adjacent copper(II) ions. The Schiff base is coordinated to the copper(II) ion in its iminothiolate form via the thiolate sulfur atom, the azomethine nitrogen atom and one of the pyrazine nitrogen atoms, the overall geometry of each copper atom in the polymer being close to a square-pyramid. The complexes, [Cu(apsme)X]₂ (X = NCS⁻, Cl⁻) are dimers in which each copper atom adopts a five-coordinate near square-pyramidal geometry with an N₃S₂ coordination environment. The Schiff base coordinates as a uninegatively charged tridentate ligand chelating via the pyridine and azomethine nitrogen atoms and the thiolate sulfur atoms. A nitrogen atom of a unidentate thiocayanate or chloride ligand and a bridging sulfur atom from a second ligand completes the coordination sphere. Room temperature μ_eff values for the complexes in the solid state are in the range 1.70-2.0 μ_B typical of uncoupled or weakly coupled Cu(II) centres. Variable temperature susceptibility studies show that the chain complex displays weak ferromagnetic coupling across the pyrazine bridges, while the S-bridged dinuclear compounds display either weak ferromagnetic or weak antiferromagnetic coupling that relates to subtle bridging geometry differences. EPR studies of frozen DMF solutions give rather similar g and A_Cu values for all compounds indicative of Cu(d_x²-y²) ground state orbitals on the Cu centers.     

Synthesis, spectroscopy and thermal behavior of new lead(II) complexes derived from S-methyl/benzyldithiocarbazates (SMDTC/SBDTC): X-ray crystal structure of [Pb(SMDTC)(NO3)2]

Lead(II) complexes of S-methyldithiocarbazate (SMDTC), [Pb(SMDTC)(NO₃)₂] (1) and S-benzyldithiocarbazate (SBDTC), [Pb(SBDTC)(NO₃)₂] (2) have been synthesized for the first time and characterized by elemental analysis, IR and TGA techniques. The complexes were obtained by addition of the appropriate ligand to an aqueous ethanolic solution of lead(II) nitrate in 1:1 molar ratio. The X-ray crystal structure of complex 1 has been determined by single crystal X-ray diffractometry. In complex 1, lead(II) is in a nine coordinated sphere with seven oxygen atoms of the nitrate groups and thione sulfur, β-nitrogen of neutral bidentate NS chelating ligand. Three nitrate groups act as bidentate chelating whereas the fourth nitrate group is coordinating to the central lead(II) and at the same time it bridges with neighboring lead(II) atom. Coordination geometry of the central lead(II) atom has a tricapped trigonal prismatic arrangement with streochemically inactive lone pair. The lead atoms are linked into polymeric chains and these chains form twin polymeric ribbons linked through bridging oxygen atoms. The N-H?O hydrogen bond network between N_SMDTC and O_nitrate atom leads to self-assembled molecular conformation and stabilizes the crystal structure. The complex 2 with similar spectral and thermal behavior is expected to have a tricapped trigonal prismatic structure. The thermal behavior studies shows that the complexes start to decompose at relatively low temperature (ca. 110 °C) to give PbS residue.     

Synthesis, characterization and crystal structure of a monomeric and a macrocyclic copper (II) complex with a large cavity using benzylacetylacetone ligand

The bidentate ligand benzylacetylacetone was used to synthesize the Cu(II) complexes 1 and 2 without and with 4,4^′-bipyridine ligand, respectively. The complexes were characterized by analytical and spectroscopic studies. The mononuclear complex [Cu(C₁₀H₉O₂)₂] (1) has been synthesized by the reaction of copper acetate with the ligand whereas the tetranuclear complex [Cu₄(4,4^′-bpy)₄(C₁₀H₉O₂)₄(C₂H₃O₂)₄] (2) has been synthesized by the reaction of copper acetate with the ligand followed by the addition of 4,4^′-bipyridine. The X-ray analysis shows that the complex 1 has square planar geometry and the complex 2 has square pyramidal geometry around the metal centers. The thermogravimetric studies showed that the complexes undergo decomposition in multiple steps.     

Aromatic N-oxide bridged copper(II) coordination polymers: Synthesis, characterization and magnetic properties

The complexes [Cu₂(o-NO₂-C₆H₄COO)₄(PNO)₂] (1), [Cu₂(C₆H₅COO)₄(2,2′-BPNO)]_n (2), [Cu₂(C₆H₅COO)₄(4,4′-BPNO)]_n (3), [Cu(p-OH-C₆H₄COO)₂(4,4′-BPNO)₂·H₂O]_n (4), (where PNO = pyridine N-oxide, 2,2′-BPNO = 2,2′-bipyridyl-N,N′-dioxide, 4,4′-BPNO = 4,4′-bipyridyl-N,N′-dioxide) are prepared and characterized and their magnetic properties are studied as a function of temperature. Complex 1 is a discrete dinuclear complex while complexes 2-4 are polymeric of which 2 and 3 have paddle wheel repeating units. Magnetic susceptibility measurements from polycrystalline samples of 1-4 revealed strong antiferromagnetic interactions within the {Cu₂}⁴⁺ paddle wheel units and no discernible interactions between the units. The complex 5, [Cu(NicoNO)₂·2H₂O]_n·4nH₂O, in which the bridging ligand to the adjacent copper(II) ions is nicotinate N-oxide (NicoNO) the transmitted interaction is very weakly antiferromagnetic.     

A pyridine adduct of bis(di-iso-butyldithiocarbamato-S,S′)cadmium(II): Multinuclear (C, N, Cd) CP/MAS NMR spectroscopy, crystal and molecular structure, and thermal behaviour

Crystalline bis(N,N-di-iso-butyldithiocarbamato-S,S′)(pyridine)cadmium(II) - adduct 1 was prepared and studied by means of multinuclear ¹³C, ¹⁵N, ¹¹³Cd CP/MAS NMR spectroscopy, single-crystal X-ray diffraction and simultaneous thermal analysis (STA). In molecular structure 1, the cadmium atom coordinates with four sulphur atoms and one nitrogen atom of pyridine, forming a coordination polyhedron [CdS₄N], whose geometry is an almost ideal tetragonal pyramidal (C_4v). The coordinated py molecule is in the apical position, while two structurally non-equivalent di-iso-butyldithiocarbamate ligands, playing the same terminal S,S′-chelating function, define the basal plane. To characterise additionally the structural state of the cadmium atom in this fivefold coordination, ¹¹³Cd chemical shift anisotropy (CSA) parameters, δ_aniso and η, were calculated from experimental MAS NMR spectra that revealed an almost axially symmetric ¹¹³Cd chemical shift tensor. From a combination of TG and DSC measurements taken under an argon atmosphere, we found that the mass of adduct 1 is lost in two steps involving initial desorption of coordinated py molecules with subsequent thermal destruction of liberated cadmium(II) di-iso-butyldithiocarbamate, with yellow-orange, fine-powdered solid CdS as the final product.     

Copper and manganese complexes with C2-multitopic ligands. X-ray crystal structure of [Cu(N,N′-bis[(S)-prolyl]phenylenediamine)H2O]. Catalytic properties

Eight mononuclear complexes with multitopic C₂-symmetry ligands, [Cu(L)]ClO₄, [Mn(L)Cl(H₂O)]PF₆, (L=N,N′-bis[(S)-prolyl]phenylenediamine (1), N,N′-bis[(S)-N-benzylprolyl]phenylenediamine (2), N,N′-bis{[(S)-pyrrolidin-2-yl]methyl}phenylenediamine (3), N,N′-bis-{[(S)-N-benzyl-pyrrolidin-2-yl]methyl}phenylenediamine (4)) have been prepared and characterised by analytical (elemental analysis, and mass spectroscopy) and FT IR, NMR and electronic spectroscopies. The data show that the ligands are neutral and coordinate to the metal in a tetradentate manner. The N,N′-bis[(S)-prolyl]phenylenediamine ligand also appears as an anionic species, (LH-2), and the single crystal structure determination of the respective complex, [Cu(1)]H₂O, is reported. This new family of Cu-complexes catalyse the cyclopropanation of styrene with ethyl and t-butyl diazoacetate to afford cis/trans 2-phenylcyclopropan-1-carboxylates with good yields and selectivity against dimerisation and low ee (<10%). On the other hand, the manganese and copper complexes also catalyse the oxidation of organic sulfides to sulfoxides with high selectivity, and moderate to low enantioselectivity. If an excess of oxidant were used the reaction yields sulfone as only product with excellent yield.     

Synthesis, crystal structure, DNA binding and photo-induced DNA cleavage activity of (S-methyl-L-cysteine)copper(II) complexes of heterocyclic bases

Ternary S-methyl-L-cysteine (SMe-l-cys) copper(II) complexes [Cu(SMe-L-cys)(B)(H(2)O)](X) (1-4), where the heterocyclic base B is 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyridoquinoxaline (dpq, 3) and dipyridophenazine (dppz, 4), and X is ClO(4)(-) (1-3) or NO(3)(-) (4), are prepared and their DNA binding and cleavage properties studied. Complexes 2 and 4 are structurally characterized by X-ray crystallography. Both the crystal structures show distorted square-pyramidal (4+1) CuN(3)O(2) coordination geometry of the complexes in which the N,O-donor S-methyl-L-cysteine and N,N-donor heterocyclic base bind at the basal plane with a water molecule as the axial ligand. In addition, the dppz structure shows the presence of a 1D-chain formed due to covalent linkage of the carboxylate oxygen atom belonging to another molecule at the elongated axial site. The crystal structures show chemically significant non-covalent interactions like hydrogen bonding involving the axial aqua ligand and pi-pi interactions between dppz ligands. The complexes display a d-d band in the range of 605-654 nm in aqueous dimethylformamide (DMF) solution (9:1 v/v). The redox active complexes show quasireversible cyclic voltammetric response near 0.1 V in DMF assignable to the Cu(II)/Cu(I) couple. The complexes show good binding affinity to calf thymus (CT) DNA giving the order: 4 (dppz)>3 (dpq)>2 (phen)>1 (bpy). The intrinsic binding constants, obtained from UV-visible spectroscopic studies, are 1.3x10(4) and 2.15 x 10(4) M(-1) for 3 and 4, respectively. Control DNA cleavage experiments using pUC19 supercoiled (SC) DNA and minor groove binder distamycin suggest major groove binding propensity for the dppz complex, while the phen and dpq complexes bind at the minor groove of DNA. Complexes 2-4 show DNA cleavage activity in dark in the presence of a reducing agent 3-mercaptopropionic acid (MPA) via a mechanistic pathway involving formation of hydroxyl radical as the reactive species. The complexes also show efficient photo-induced DNA cleavage activity on irradiation with a monochromatic UV light of 365 nm in absence of any external reagent. The cleavage efficiency follows the order: 3>4>2. The complexes exhibit significant DNA cleavage activity on irradiation with visible light of 633 nm. Control experiments show inhibition of cleavage in presence of singlet oxygen quenchers like sodium azide, histidine and enhancement of cleavage in D(2)O, suggesting formation of singlet oxygen as a reactive species in a type-II process. The photosensitizing effect of the thiomethyl group of the amino acid is evidenced from the observation of significant DNA photocleavage activity of the phen complex 2 as the phen ligand itself is not a photosensitizer.     

Anticancer and antifungal activity of copper(II) complexes of quinolin-2(1H)-one-derived Schiff bases

The condensation of substituted aromatic aldehydes with 7-amino-4-methyl-quinolin-2(1H)-one (1) has lead to the isolation of quinolin-2(1H)-one derived Schiff bases (2-14). The copper(II) complexes (2a-14a) of the ligands were also prepared, and together with their corresponding free ligands were fully characterised by elemental analyses, spectral methods (IR, ¹H and ¹³C NMR, AAS, UV-Vis), magnetic and conductance measurements. The bidentate ligands coordinated to the copper(II) ion through the deprotonated phenolic oxygen and the azomethine nitrogen of the ligands in almost all cases. X-ray crystal structures of two of the complexes, 5a and 8a, confirmed the bidentate coordination mode. All of the compounds were investigated for their antimicrobial activities against the fungus, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to have excellent anti-Candida activity but were inactive against Staphylococcus aureus and Escherichia coli. Selected compounds (2-8 and 2a-8a) were also screened for their in vitro anticancer potential using the human hepatic carcinoma cell line, Hep-G₂. Several derivatives were shown to be active comparable to that of cisplatin.     

Platinum(II) imidazo[4,5-f]-1,10-phenanthroline chloride and thiolate complexes: Synthesis and crystal structures

The planar aromatic imidazo[4,5-f]-1,10-phenanthroline ligands have been used to prepare platinum(II) chloride and thiolate complexes. The X-ray structures of two thiolate compounds are reported, which show column-like packing in the solid state due to intermolecular aromatic π-π interactions. The compounds absorb moderately in the visible region, owing to {charge-transfer-to-diimine} electronic transition.     

Up-regulation of Brain N-Methyl- -aspartate Receptors Following Multiple Intracerebro- ventricular Injections of [ -Pen, -Pen] Enkephalin and [ -Ala, Glu]deltorphin II in Mice

Bhargava, H. N., S. Kumar and J. T. Bian. Up-regulation of brain N-methyl- -aspartate receptors following multiple intracerebroventricular injections of [ -Pen², -Pen⁵]enkephalin and [ -Ala², Glu⁴]deltorphin II in mice. Peptides 18(10) 1609–1613, 1997.—The effects of chronic administration of [ -Pen², -Pen⁵]enkephalin and [ -Ala², Glu⁴]deltorphin II, the selective agonists of the δ₁- and δ₂-opioid receptors, on the binding of [³H]MK-801, a noncompetitive antagonist of the N-methyl- -aspartate receptor, were determined in several brain regions of the mouse. Male Swiss-Webster mice were injected intracerebroventricularly (i.c.v.) with [ -Pen², -Pen⁵]enkephalin or [ -Ala², Glu⁴]deltorphin II (20 μg/mouse) twice a day for 4 days. Vehicle injected mice served as controls. Previously we have shown that the above treatment results in the development of tolerance to their analgesic activity. The binding of [³H]MK-801 was determined in brain regions (cortex, midbrain, pons and medulla, hippocampus, striatum, hypothalamus and amygdala). At 5 nM concentration, the binding of [³H]MK-801 was increased in cerebral cortex, hippocampus, and pons and medulla of [ -Pen², -Pen⁵]enkephalin treated mice. In [ -Ala², Glu⁴]deltorphin II treated mice, the binding of [³H]MK-801 was increased in cerebral cortex and hippocampus. The changes in the binding were due to increases in the B_max value of [³H]MK-801. It is concluded that tolerance to δ₁- and δ₂-opioid receptor agonists is associated with up-regulation of brain N-methyl- -aspartate receptors, however, some brain areas affected differ with the two treatments. The results are consistent with the recent observation from this laboratory that N-methyl- -aspartate receptors antagonists block tolerance to the analgesic action of δ₁- and δ₂-opioid receptor agonists.     

Synthesis, characterization, spectroscopic and electrochemical properties of trans,trans,trans-bis(triphenyl phosphine) bis(aroyl hydrazonato)ruthenium(II) complexes

Four ruthenium (II) complexes of general formula Ru(PPh₃)₂(L)₂ have been synthesized and characterized. The spectroscopic and cyclic voltammetric studies of these complexes are also reported. X-ray crystal structure determination of two of the complexes reveal that Ru(II) occupies trans,trans,trans-(t,t,t) N₂O₂P₂ centrosymmetric octahedral environments, with the ligand pair occupying the equatorial plane. ³¹P NMR confirms the presence of two trans-PPh₃ groups in all the complexes. The transformation of the complexes in dichloromethane solution is studied by spectrophotometry and ³¹P NMR spectroscopy.