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.

An approach to metal-assisted DNA base pairing: novel beta-C-nucleosides with a 2-aminophenol or a catechol as the nucleobase.

The metal-chelating beta-C-nucleoside having a phenylenediamine moiety as the nucleobase was previously found to form a stable 2:1 complex with a Pd(2+) ion in aqueous media, where hydrogen bonding is replaced by metal coordination in the base pairing, thereby creating a novel hybridization motif in duplex DNA. In this regard, we have further designed two types of artificial beta-C-nucleosides possessing a metal-chelating site (a 2-aminophenol or a catechol) as the nucleobase moiety. These artificial nucleosides are directed toward controlling the net charges of the metal-assisted base pairs. This paper describes convenient syntheses of the artificial nucleosides bearing a 2-aminophenol or a catechol moiety. Each nucleoside was directly synthesized through 2'-deoxy derivative via a Friedel-Crafts coupling reaction as the key step between the aromatic ring and ribose moiety, whereas the nucleoside having a phenylenediamine moiety was prepared in rather longer steps through an RNA type intermediate followed by the removal of 2'-hydroxyl group.

An alternative base-pairing of catechol-bearing nucleosides by borate formation.

A chelator-type beta-C-nucleoside having a catechol ligand as the nucleobase was found to form a stable 2:1 complex with trimethyl borate, which was characterized by 1H-NMR and electrospray ionization time-of-flight (ESI-TOF) mass spectroscopies. Both phosphoramidite and phosphotriester derivatives of this nucleoside were also prepared as synthetic precursors for DNA oligomer syntheses.

Dynamic regulation of prothoracic gland ecdysteroidogenesis: Manduca sexta recombinant prothoracicotropic hormone and brain extracts have identical effects.

Multiple assays were conducted in order to determine if the recently available recombinant prothoracicotropic hormone (rPTTH) from Manduca sexta is identical, or similar, to the natural hormone and if results from its use in a variety of assays confirm, or are inconsistent with, previous studies over the past 20years on PTTH action using brain extract. Brain extracts and rPTTH showed similar, if not identical, effects on the cell biology of Manduca prothoracic gland cells with the following results: increased levels of cAMP (adenosine 3':5' cyclic monophosphate) synthesis; requirement for extracellular Ca(2+) in in vitro studies; ecdysteroidogenesis stimulation in vitro; stimulation of general and specific protein synthesis; immunocytochemical identification of the two lateral cells in each brain hemisphere as the source of PTTH (the prothoracicotropes); the ability of antibodies to rPTTH to inhibit ecdysteroidogenesis stimulation in vitro; and the multiple phosphorylation of the ribosomal protein S6. The data revealed that brain extract and rPTTH show equivalent effects in all of the assays, indicating that this rPTTH is the natural PTTH of Manduca and that the data generated with brain extracts over the past two decades are indeed relevant.

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.

Artificial DNAs with metal-assisted base pairs.

Two types of artificial beta-C-nucleosides, 2 and 3, were newly synthesized, which possess a metal chelating site (2-aminophenol and catechol, respectively) at the nucleobase moiety. These nucleosides are expected to form metal-assisted base pairs in oligonucleotides and thereby to control high-order structures and functions of DNAs.

Frequency-upconverted organic crystal.

The fluorescent characteristics of Troger's base have been investigated experimentally. A one-photon-induced fluorescent spectrum was observed, and the peak wavelength was at 337 nm with a full width at half-maximum of ~85nm . The violet radiation of the Troger's base crystal could result from the pi(*) -pi transition of the benzenoid pi bond. Two-photon-pumped frequency-upconverted fluorescence was obtained, which is a wideband emission with the main peak wavelength at 337 nm and a subordinate peak. Donor groups and acceptor groups of electrons in the aromatic rings strengthen the two-photon-pumped frequency-upconverted fluorescence.

[Nonrheumatic calcification of the mitral valve in patients with stenotic calcified bicuspid aortic valve].

The pathogenesis of nonrheumatic calcification of the mitral valve was investigated by analyzing the clinical and echocardiographic characteristics of patients with mitral valvular calcification without any findings suggestive of rheumatic heart disease or infective endocarditis. Calcification of the mitral valve was observed in nine patients, who all had calcified stenotic (aortic valve area < 1 cm2) bicuspid aortic valve. Calcification of the mitral valve was localized to the basal portion of ventricular aspect of the anterior mitral leaflet and contiguous to that of the aortic valve. Mobility and thickness of the mitral leaflet was normal except for the calcified portion. Calcification of the mitral valve was not contiguous to posterior mitral annular calcification nor was related to direction of aortic regurgitant flow. In patients with calcified stenotic bicuspid aortic valve, calcification of the mitral valve was not associated with location of the two aortic cusps, aortic valve area, aortic valvular peak pressure gradient, direction of the left ventricular outflow, end-diastolic left ventricular outflow tract dimension, end-diastolic dimension of the aortic annulus, incidence of aortic regurgitation, calcification of the aortic arch, or risk factors of atherosclerosis. Six patients with mitral valvular calcification had aortic valve replacement. Preoperative coronary angiogram of these patients was normal. Calcification of the aortic valve was on the ventricular and aortic aspects. The calcification of the aortic valve, anterior mitral ring, or anterior mitral leaflet was not rheumatic in these six patients. Rheumatic disease, risk factors of atherosclerosis, mechanical stress by left ventricular outflow or aortic regurgitant flow, or mitral annular calcification did not appear to be related to mitral valvular calcification. The distribution of aortic and mitral valvular calcification suggested that the calcification of the mitral valve was due to progression of calcification of the bicuspid aortic valve.

Differential contribution of metal complexation and dimerization to the chemotherapeutic potential of bicyclen-Zn2II complex against human immunodeficiency virus.

1,1'-(m-Xylenediyl)-bis(1,4,7,10-tetraazacyclododecane)-Z n2II complex (m-xylenediyl-bicyclin-Zn2II), a potent inhibitor of human immunodeficiency virus (HIV), was obtained from cyclin by a combination of dimerization and metal complexation. The ratio of median cytotoxic concentration against host cells (CC50) and median effective concentration against HIV cytopathogenicity (EC50), referred to as the selectivity index (SI), was regarded to be a measure of anti-HIV activity. These two chemical modifications contributed to a potent, in vitro anti-HIV activity of m-xylenediyl-bicyclin-Zn2II by respectively increasing the CC50 and decreasing the EC50 in comparison with those of cyclin.

Inactivation of bleomycin by an N-acetyltransferase in the bleomycin-producing strain Streptomyces verticillus.

Bleomycin-producing Streptomyces verticillus ATCC15003 possesses a bleomycin acetyltransferase which inactivates the drug in the presence of acetyl coenzyme A. The site of acylation in enzymically prepared acetylbleomycin A2 was determined by nuclear magnetic resonance analysis; the primary amino group of the beta-aminoalanine moiety of bleomycin was acetylated Acetylbleomycin A2 had no detectable antibacterial activity and did not induce in vitro DNA degradation.

Inhibition of human immunodeficiency virus proliferation by macrocyclic polyamines and their metal complexes.

The macrocyclic polyamines, cyclen and cyclam, and their derivatives have been tested for inhibitory activity against the cytopathogenic effect (CPE) of human immunodeficiency virus type 1 strain HTLV-IIIB (HIV-1IIIB) on CD4+ human lymphoblastoma MT-4 cells. Cyclam and its derivatives were complexed with a variety of transition metal ions NiII, ZnII, CuII, FeIII and CoIII. The divalent metal complexes effected lower toxicity and greater anti-HIV-1 activity, while the trivalent metal complexes had no effect on HIV-1-dependent CPE. When dimerized, the anti-HIV activity of monomers was significantly enhanced. A potent inhibition of CPE by biscyclam was transiently observed 4 d after the virus infection, but was not seen at 6 d due to severe toxicity. The toxicity of biscyclam, referred to as delayed toxicity, could be overcome by a metal complexation. The strain specificities of biscyclams were further studied by testing their effects on syncytium formation between HIV-infected and uninfected human acute lymphoblastic leukemia MOLT-4 cells. The 50% inhibitory concentrations of biscyclams against HIV-2GH-1-dependent syncytium formation were less than one hundredth those for the other HIV strains (HIV-1IIIB, HIV-1RF and HIV-1SF-2).

[Echocardiographic assessment of aortic regurgitation and aortic root dilatation in bicuspid aortic valve].

Aortic regurgitation (AR) and aortic root dilatation in 29 consecutive patients with bicuspid aortic valves but without aortic root disease (20 males, and 9 females: aged 27-85 years) were studied using two-dimensional echocardiography. The normal ranges of aortic root dimensions were calculated from values of 185 normal subjects, as 95% confidence intervals. AR was observed in 17 patients by color flow mapping. In 12 of the 17 AR patients, no significant lesion of the aortic cusp was detected by two-dimensional echocardiography. These 12 AR patients were compared with 12 patients without AR. Increase in dimension of the aortic root was relatively frequent in the 12 AR patients at the aortic annulus (AA) (67 vs 17%, p < 0.05), and at the sinus of Valsalva (A1) (67 vs 17%, p < 0.05). At the ascending aorta 5 mm distal to the sinus of Valsalva (A2), the difference was not significant (58 vs 17%, p < 0.09). The 12 bicuspid AR patients without significant lesions of the aortic cusp were compared with 41 AR patients with normal tricuspid aortic valves. The frequencies of cases with increased aortic root dimension were 67 vs 46% (ns) at the AA, 67 vs 22% (p < 0.05) at A1 and 58 vs 5% at A2 (p < 0.01). Thus, aortic annular dilatation was thought to be the cause of AR in bicuspid and tricuspid aortic valves without significant lesions of the aortic cusps, and generalized dilatation of the aortic root was more frequent in bicuspid AR patients than in tricuspid AR patients.(ABSTRACT TRUNCATED AT 250 WORDS)