Effect of imatinib on DOCA-induced myocardial fibrosis in rats through P38 MAPK signaling pathway.

OBJECTIVE: To explore the role of imatinib in desoxycorticosterone acetate (DOCA)-induced myocardial fibrosis in rats by the p38 mitogen-activated protein kinase (MAPK) signaling pathway. MATERIALS AND METHODS: Normal group (n=20), DOCA induction group (n=20), and imatinib treatment group (treatment group, n=20) were set up. Then, the cardiac function was examined via magnetic resonance imaging (MRI) and echocardiography (ECG) on the 21st d after modeling. Alkaline phosphatase (ALP) and myocardial function index creatine kinase-MB (CK-MB) were detected. The enzyme-linked immunosorbent assay (ELISA) was performed to measure tumor necrosis factor-gamma (TNF-γ) and interleukin-6 (IL-6). Hematoxylin-eosin (HE) staining assay was carried out to observe the pathological changes in myocardial tissues. Quantitative Polymerase Chain Reaction (qPCR) and Western blotting were employed to measure the expression levels of important myocardial fibrosis-related genes [checkpoint kinase 1 (Chek1) and alpha-smooth muscle actin (α-SMA)], as well as genes and proteins of the p38 MAPK signaling pathway. RESULTS: In comparison with the normal group, DOCA induction group had significantly lowered fractional shortening (FS, %) and ejection fraction (EF, %), but overtly increased left ventricular end-diastolic dimension (LVEDd) and left ventricular end-systolic dimension (LVESd), as well as levels of serum ALP, alanine aminotransferase (ALT), and CK-MB. Besides, the levels of TNF-γ, IL-6, and IL-1ß were notably raised in the DOCA induction group. HE staining results showed that myocardial injury was more severe in DOCA induction group. The results of the gene detection revealed that the expression levels of Chek1, α-SMA, p38 MAPK, and JNK were evidently higher in DOCA induction group than those in the imatinib treatment group (p<0.05), and the expression of p38 MAPK protein in the rat myocardial tissues was remarkably lower in the treatment group than that in the DOCA induction group (p<0.05). CONCLUSIONS: Imatinib can regulate the repair of myocardial injury caused by DOCA-induced myocardial fibrosis in rats by repressing the p38 MAPK signaling pathway.

Bis[mu-2-[(1,5-diaza-1-cyclooctyl)-methyl]phenolato-N,N',O:O]bis-[chlorozinc(II)]diacetone solvate: design of a square-pyramidal ZnN2O2Cl complex.

The title complex, [Zn(2)(C(13)H(19)N(2)O)(2)Cl(2)].2C(3)H(6)O, resides on a crystallographic inversion center. The two Zn(II) centers bridged by the phenoxo groups are in pentacoordinated distorted square-pyramidal coordination environments with an intramolecular Zn...Zn distance of 3.175 (3) A. The mesocyclic ligand takes a boat-chair conformation and an H atom from the 1,5-diazacyclooctane ring effectively blocks the axial coordination site opposite the Cl ligand to form the ZnN(2)O(2)Cl geometry. The crystal structure is stabilized by a N-H...O hydrogen bond between the amino group and an acetone molecule.

Novel boxlike dinuclear or chain polymeric silver(I) complexes with polypyridyl bridging ligands: syntheses, crystal structures, and spectroscopic and electrochemical properties.

The syntheses, characterization, crystal structures, and photophysical and electrochemical properties of two dinuclear and two polymeric Ag(I) complexes with three polypyridyl ligands, 2,3-di-2-pyridylquinoxaline (L(1)), 2,3-di-2-pyridyl-5,8-dimethoxyquinoxaline (L(2)), and 2,3,7,8-tetrakis(2-pyridyl)pyrazino[2,3-g] quinoxaline (L(3)), are described. The structures of the two boxlike dinuclear complexes with L(1) and L(2) and two chemically the same but differently crystallized one-dimensional zigzag chain coordination polymers also consisting of boxlike dinuclear subunits have been elucidated by X-ray analysis. [AgL(1)(CH(3)CN)](2)-(BF(4))(2).2CHCl(3) (1): monoclinic, C2/c; a = 28.631(2), b = 12.2259(11), c = 14.3058(12) A; beta = 99.180(2) degrees; Z = 4. [AgL(2)(CH(3)CN)(2)](2)(ClO(4))(2) (2): triclinic, P1; a = 12.3398(2), b = 13.750(2), c = 14.326(7) A; alpha = 83.494(3), beta = 74.631(3), gamma = 76.422(3) degrees; Z = 4. [[Ag(2)L(3)(NO(3))(2)].CH(3)CN](infinity) (3a): monoclinic, P2(1)/c; a = 9.5836(8), b = 13.4691(12), c = 14.0423(12) A; beta = 107.753(2) degrees; Z = 4. [Ag(2)L(3)()(NO(3))(2)](infinity) (3b): monoclinic, P2(1)/c; a = 8.4689(6), b = 16.0447(12), c = 11.7307(8) A; beta = 102.051(1) degrees; Z = 2. The structures of the dinuclear complexes 1 and 2 are similar to each other, with the two intramolecular Ag(I) centers of each complex being spanned by two ligands thus forming a unique boxlike cyclic dimer. In 1, each Ag(I) center is four-coordinated by three nitrogen atoms of two L(1) ligands and a CH(3)CN nitrogen donor, taking a distorted tetrahedral coordination geometry. The coordination environment of Ag(I) in 2 is similar to that in 1, except the formation of an additional weak coordination bond with the oxygen atom of the methoxy group of L(2). The structures of 3a,b are very similar to each other, except for the stacking patterns in the crystal lattices, and the cyclic boxlike dinuclear unit, which is similar to the structure of 1, constitutes the fundamental building block to form the one-dimensional zigzag chain structures due to the "end-on" nature of L(3). 1-3 exhibit metal-perturbed intraligand transitions in solution in 360-390 nm regions. Cyclic voltammetric studies of these complexes show the presence of reduction peak at approximately -0.5 V vs Fc(+/0). In the solid state at 77 K, they exhibit broad emission that may be assignable to originate from the metal-perturbed intraligand transitions.

Bis(1,5-diazacyclooctane-N,N')nickel(II) dibromide.

The crystal structure of the title complex, [Ni(C(6)H(14)N(2))(2)]Br(2), consists of discrete [Ni(C(6)H(14)N(2))(2)](2+) cations and bromide counter-anions. The Ni(II) ion is at the center of symmetry and is four-coordinated by four nitrogen donors of the mesocyclic ligand 1,5-diazacyclooctane (DACO) [Ni-N 1.935 (2)-1.937 (2) A]. The coordination geometry of Ni(II) can be considered as square planar and both DACO ligands take the boat-chair conformation. The bromide anions are hydrogen bonded with the nitrogen donors of the ligands to form a macrocycle-like ring system.

Varying coordination modes and magnetic properties of copper(II) complexes with diazamesocyclic ligands by altering additional donor pendants on 1,5-diazacyclooctane.

A series of new diazamesocyclic ligands based on a diazamesocycle, 1,5-diazacyclooctane (DACO), functionalized by additional donor groups--1,5-bis(N-1-methylimidazol-2-ylmethyl)-1,5- diazacyclooctane (L1), 1-(2-hydroxybenzyl)-1,5-diazacyclooctane (HL2), 1,5-bis(2-hydroxybenzyl)-1,5-diazacyclooctane (H2L3), and 1-(N-1-methylimidazol-2-ylmethyl)-1,5-diazacyclooctane (L4)--and their Cu(II) complexes have been synthesized and characterized. Single-crystal X-ray diffraction analysis of the four Cu(II) complexes revealed that L1 forms a five-coordinate mononuclear complex, HL2 a N3- mu-bridged binuclear complex, H2L3 an oxygen mu-bridged trinuclear complex, and L4 a one-dimensional zigzag coordination polymeric complex with Cu(II). [CuL1ClO4](ClO4) (I): a = 12.194(2) A, b = 13.351(3) A, c = 14.473(3) A, beta = 107.10(3) degrees, Z = 4. [CuL2(N3)]2 (II): a = 8.1864(6) A, b = 18.141(2) A, c = 9.3307(7) A, beta = 103.662(6) degrees, Z = 2. [Cu3(L3)2Cl2] (III): a = 10.7296(13) A, b = 13.7707(17) A, c = 13.5523(17) A, beta = 106.350(3) degrees, Z = 2. ([CuL4Cl]2ClO4) infinity (IV): a = 7.279(1) A, b = 23.695(5) A, c = 19.308(4) A, beta = 100.28(3) degrees, Z = 8. All four complexes crystallize in the monoclinic crystal system with the P2(1)/c space group, and each Cu(II) center coordinated with DACO is pentacoordinated with a distorted square-pyramidal or trigonal-bipyrimidal coordination environment. In complex IV, the binuclear cation unit [CuL4Cl]2(2+) constitutes the fundamental building block of an infinite alternating zigzag chain structure, and the binuclear unit contains two types of geometries around the Cu(II) centers: the Cu(1) center is a distorted square-pyramidal environment, while the Cu(2) is a distorted trigonal-bipyramidal coordination environment. To the best of our knowledge, this is the first Cu(II) complex of a diazamesocyclic ligand with an infinite polymeric structure. The magnetic properties of complexes II, III, and IV have been investigated by variable-temperature magnetic susceptibility measurements in the solid state. The obtained parameters are 2J = 2.06 cm-1 (II), -345.56 cm-1 (III), and -2.60 cm-1 (IV), which differ greatly from ferromagnetic to weak and strong antiferromagnetic coupling. These results unequivocally indicate that the nature of the pendant arms is a key factor governing the structure and properties of the complexes; therefore, the coordination modes and properties of the metal complexes of a diazamesocycle can be controlled by altering the pendant donors on it. Magneto-structural correlation has been precisely analyzed, and the solution properties of these complexes have also been described.