Synthesis of a new 2,2'''':6'''',2''''''''-terpyridine derivative and its coordination property

A novel compound, (E)-4'-(4-(but-1-en-3-ynyl)phenyl)-2,2':6',2'-terpyridine 1 was synthesized from 4'-(4-bromomethylphe- nyl)-2,2':6',2'-terpyridine phosphonium salt 2 and propargylaldehyde via Wittig reaction, and characterized by EI-MS and 1H NMR as well as elemental analysis. The spectral changes of the compound in the presence of transition metal ions, such as Cu(Ⅰ) or Zn(Ⅱ), are investigated.     

SOLID-PHASE SYNTHESIS OF 2''''—5'''' OLIGOADENYLATE——2''''—5''''A CORE

With phosphotriester approach, the 2'—5' linked oligonucleotide——2'—5'A core was synthesized by using cross-linked polyacrylmorpholide resin as the support and the mesitylene sulfonyl chloride and N-methylimidazole as the condensing agent. Synthesizing the 2'—5'A core with this method has not yet been described. The yields that each of the protected monomers was attached to the polymeric support were satisfactory, i.e., 100%, 60% and 91% respectively.For the synthesis, we improved the methods for preparing the polymeric support and a series of intermediates. For this reason, the yields of the products were markedly increased and the operations to separate the products from the by-products and reagents were simplified.     

Synthesis and Structure of trans-1,2-Bisaromatic Heterocycle Substituted Cyclopropanes

Trans-1,2-bis(2'-(5 '-phenyl-1 ',3',4'-oxadiazolyl)) cyclopropane (BDCP) and its eleven substituted novel derivatives were synthesized. Besides four derivatives of l,2-bis(2'-(5'-phenyl-l ' , 3 ' , 4 ' -ox-adiazo1yl))ethane (BPDS) were also synthesized as model compounds. The crystal structure of ethyl BDCP was determined and the cyclopropane ring was found to be able to transmit conjugation between the aromatic groups directly bonding with it by studying the ultraviolet and fluorescent spectra of the above compounds.     

Laser photolysis of interaction of poly-guanylic acid (5'''') with anthraquinone-2-sulfonate

The electron transfer reaction between triplet anthraquinone-2-sulfonate and poly-guanylic acid (5') in CH3CN-H2O (97 : 3) has been investigated by 248 nm (KrF) laser flash photolysis. The transient absorption spectra and kinetics obtained from the interaction of triplet anthraquinone-2-sulfonate and poly[G] demonstrate that the primary ionic radical pair, radical cation of poly[G] and radical anion of anthraquinone-2-sulfonate have been detected simultaneously. The free energy changes in the process of the electron transfer were also calculated.     

MECHANISM OF INTERFERON ACTION Ⅲ——SIGNIFICANCE OF _(ppp)A_(2'P5')A_(2'P5')A IN THE ANTIVIRAL ACTION OF INTERFERON

This paper is to evidence that the antiviral effect of _(ppp)A_(2'p5')A_(2'p5')A(2'-5'P_3A_3) could cover a wide spectrum of viruses, the RNA viruses such as influenza H_3N_2/77, influenza H_1N_1/77, ECHO_(11), rhino, Sendai, Sindbis and VSV, and the DNA viruses such as herpes (type Ⅰ). In addition, the antiviral effect of 2'-5'P_3A_3 on ECHO_(11) virus, as compared with other viruses, is more efficient than that of IFN itself. It seems likely that 2'5'P_3A_3 plays an important role in the antiviral action of IFN. After comparing the action of 2'-5'P_3A_3 with interferon (IFN), it has appeared that the action of 2'-5'P_3A_3 is something parallel to that of IFN for most viruses. For a few viruses, however, considerable differences have been observed.     

Preparation and spectroscopic properties of 2'''',5''''-dideoxynucleosidylcobalamins

Two new coenzyme B12 analogues, 2',5'-dideoxycytidylcobalamin (2a) and 2',5'-dide-oxyuridinylcobalamin (2b), and two others, 2',5'-dideoxyadenosylcobalamin (2c), and 5'-deoxy-thymidylcobalamin (2d) were prepared by an improved method. All the four analogues were investigated by UV-vis and 2D 1H NMR spectroscopy. The comparisons and discussion about their spectroscopic properties were done.     

STUDY ON THE MECHANISM OF INTERFERON ACTION (Ⅺ)——EFFECT OF pppA2''''p5''''A2''''p5''''A ON THE LEVEL OF cAMP AND cGMP IN MACROPHAGES

In this paper, the increase of cellular cAMP and cGMP levels in macrophages induced bypppA2'p5'A2'p5'A (briefly 2'-5'P_3A_3) is first reported. The optimal concentration of 2'-5'P_3A_3 for the elevation of cellular cGMP to the highest level is 10~(-7)-10~(-6)mol/L, while thatfor cAMP is 10~(-7)mol/L. The time for cGMP to reach its peak value is 15 min and that forcAMP is 2 h, when the cells are treated with 2'-5' P_3A_3 at 10~(-7)mol/L, which is the optimalconcentration for developing biological effect of macrophages (phagocytosis). These resultssuggest that cGMP and cAMP may be related to, or may be the mediators for, 2'-5'P_3A_3action.     

双核Cd(Ⅱ)配合物[Cd2(C22H14N4)2Cl2(N3)2]2·H2O的合成与晶体结构

A dinuclear Cd(Ⅱ) complex [Cdz (N3)2LzCl2]2·H2O (1) [L=4'-(4-eyanophenyl)-2,2':6',2"-terpyridine]was synthesized by reaction of ligand L with CdCl2 and NaN3 using solvothermal method and its structure was determined by X-ray crystal structure analysis. The structure indicates that the complex crystallizes in monoclinic, space group C2/c with a=1.644 5(16) nm, b=1.441 9(12) nm, c=1.9181(18) nm,β=100.349(11)°. V=4474(7) nm3, Z=2, Dc=1.570Mg·m-3,μ=1.120 mm-l, F(000)=2 100, and final R1=0.039 3, wR2=0.0811. The result shows a Cd(Ⅱ) ion was sixcoordinated by a tridentate 4'-(4-cyanophenyl)-2,2' :6',2"-terpyridine ligand and one bridging nitrogen atom of the azide group in the basal position and an chloride atom and the other bridging nitrogen atom of the azide group in the axialone, to form a distorted octahedral-pyramidal geometry. CCDC: 673291.     

Trinuclear Metal Complexes Based on 1,10-Phenanthroline Derivates as Catalysts for Cleavage of a RNA-Model Substrate

Two multidentate ligands 2,9-di[6'-(2″-hydroxyl-3″-methoxyphenyl)-n-2',5'-diazahexyl]-1,10-phenanthroline(LA)and 2,9-di(6'-α-phenol-n-2',5'-diazahexyl)-1,10-phenanthroline(LB)were synthesized and fully characterized.Protonation of the ligands and the stability of the complexes of the ligands with divalent metal ions were investigated.The trinuclear metal complexes [Cu(Ⅱ)and Zn(Ⅱ)] of the ligands were studied,as catalysts,for the transphosphorylation of the RNA-model substrate 2-hydroxypropyl-p-nitrophenyl phosphate(HPNP).The second-order rate constants of HPNP-hydrolysis catalyzed by M3L and M3LH-1 were obtained,which indicated that Zn3LBH-1 was the most efficient catalyst among them.The proposed mechanisms included the activation of the substrate via binding to the metal ions and intramolecular nucleophilic attack by the deprotonated C2-hydroxyl of HPNP.     

Effects of Bases on the Stabilities of Nucleoside C4'''' Radicals

C4'-H bond dissociation enthalpies of nucleosides were predicted using theoretical methods to a precision of 1-2 Kcal/mol. It was found that the stability of the C4' nucleoside radical is slightly dependent on the base. The orders of stability are dA < dG < dT < dC for deoxynucleosides and U < G < A = C for nucleosides.     

Synthesis of β-L-2'''',3''''-Dideoxy-2''''-fluoro-3''''-hydroxy-methylarabinofuranosyl Pyrimidine Nucleosides

L-Nucleosides have attracted considerable attention since many analogs have exhibited a higher antiviral potency and selectivity than their corresponding D-isomers1. In particular, (-)-(2R, 5S)-1-[(2-hydroxymethyl)-oxathiolan-5-yl]cytosine (3TC, Lamivu- dine)2,its 5-fluoro analog [(-)-FTC, Coviracil]3 and (-)--L-2',3'-dideoxy-5-fluorocytidine (L-FddC)4 are in various stages of preclinical or clinical trials as anti-HIV and anti-HBV agents. Furthermore, the introduction of a 2'--fluo…     

MECHANISM OF INTERFERON ACTION Ⅹ——ANTAGONISTIC EFFECT OF ATP ON pppA2''''p5''''A2''''p5''''A RECEPTOR

pppA2'p5'A2'p5'A (2'-5'P_3A_3) receptor may be the first one in the oligonucleotide field.But ATP can compete with 2'-5'P_3A_3 for the receptor. This raises a question whether this is anATP receptor. If not, what is the role of ATP for this receptor? Data available in this arti-cle show that ATP can bind to macrophages with saturability and reversibility. So ATPappears to be also a ligand of the receptor for 2'-5'P_2A_3. But the binding of ATP did notdevelop phagocytic effect as mentioned before~([11]). Moreover, ATP inhibited the enhancementof phagocytosis of macrophages by 2'-5'P_3A_3 when it acted together with 2'-5'P_3A_3 on mac-rophages at the same time. It is concluded that ATP is an antagonist of 2'-5'P_3A_3 receptor.When macrophages were treated with ATP prior to 2'-5'P_3A_3 and the binding sites for 2'-5'P_3A_3P were first occupied by ATP, both the binding ability and the biological effect of2'-5'P_3A_3 were all markedly blocked. The above data convincingly show that the action of2'-5'P_3A_3 is     

A thin-layer spectroelectrochemical study of 3,3'''',5,5''''-tetramethylbenzidine at SnO_2:F film optically transparent electrode

3,3',5,5'-tetramethylbenzidine (TMB) is a sensi-tive commonly-used substrate of the spectrophotomet-ric enzyme-linked immunosorbent assay (ELISA) as well as the electrochemical enzyme-linked immuno-assay[1,2]. It is more stable and of lower reagent blank than another sensitive commonly-used substrate, o-phenylenediamine. TMB is also the substrate of the most ELISA kits for clinical examination. The TMB- H2O2-horseradish peroxidase (HRP) voltammetric en-zyme immunoassay system has very…     

Preparation and properties of diuridine 3'''',5''''-boranophosphate

Diuridine 3', 5'-boianophosphate has been synthesized. Its diastereomers were separated and their configurations were tentatively assigned based on the selective snake venom phosphodiesterase (SVPDE) hydrolysis. It is found that, compared to the unmodified parent compound diuridine phosphate, the nucleophilicity and the stability of the modified compounds to SVPDE are significantly enhanced.     

MECHANISM OF INTERFERON ACTION——THE DISCOVERY OF pppA2'p5'A2'p5'A RECEPTOR

In this paper it is demonstrated that (~3H)2'-5'P_3A_3 can bind to the peritoneal macrophages from Wistar rat. This binding is strongly inhibited by cold 2'-5'P_3A_3 while the inhibiting capacity of 2'-5'P_3I_3 and 2'-5'A_3 is very small, showing that this binding is highly specific. And the binding of (~3H)2'-5'P_3A_3 is reversible, saturable and with high affinity. A Scatchard analysis of the binding data gives a linear plot, an apparent dissociation constant (Kd) about 1.3×10~(-7) M and binding sites per cell about 2.1×10~7. The above evidence shows the existence of the 2'-5'P_3A_3 receptor, a fact which, to our knowledge, has not been reported before.     

Synthesis of affinity column of phosphatidylinositol-3,4-diphosphate

Phosphatidylinositol polyphosphates (PIPx) are related with tyrosine kinase activation, cell proliferation and carcinogenesis. In order to investigate the action mechanism of PIPx, it is desirable to synthesize affinity column of PI-3,4-P2, which is expected to be able to isolate the binding proteins of PI-3,4-P2. Thyramine reacted with CH-Sepharose 4B giving column 13. The p-amino group of 3'-(1',2'-distearoyl-glyceryl)-1-(2-p-aminobenzyl)-3,4-di-O-phosphoryl-myo-inosityl phosphate (12) was diazotized, then diazo-coupled with column 13 to give PI-3,4-P2 affinity column 14. This PI-3,4-P2 affinity column is an effective tool to pick up binding proteins of PI-3,4-P2.     

MECHANISM OF INTERFERON ACTION——ACTIVATION OF MACROPHAGES AND ANTAGONISM TO a-FETO-PROTEIN BY _(ppp)A_(2'p5')A_(2'p5')A

_(ppp)A_(2'p),'A_(2'p,)'A(2'-5'P_3A_3) activates macrophages and increases the phagocytosis of macrophages from different species including human beings. This indicates that the activation of macrophages may be a general action of 2'-5'P_3A_3. This discovery broadens the effect of 2'-5'P_3A_3 beyond the antiviral field.α-Feto-protein (AFP) inhibits the phagocytosis of macrophages and may be involved in the development of hepatoma. Data presented here show that 2'-5'P_3A_3 can antagonize this suppressive effect of AFP.Methods used so far for introducing 2'-5'P_3A_3 into the cells were made with the aid of CaCl_2, etc. under conditions which may not be the same as those used clinically. It was found that 2'-5'P_3A_3 can develop its biological effect without the aid of CaCl_2, etc.     

Synthesis and Anti-SIV Activity in vitro of Novel 4,4''''-Dimethoxy-5,6,5'''',6''''- dimethenedioxy-2-alkyloxycarbonyl Biphenyl Derivatives

4,4'-Dimethoxy-5,6,5',6'-dimethenedioxy-2,2'-dimethoxycarbonyl biphenyl (DDB, 1) and its derivatives show anti-HBV and anti-HIV activities.[1] However, their poor solubility was not in favor of bioavailability.[2,3] In addition,other anti-HIV agents[4] with piperazine moiety have been investigated. Their saturated nitrogen-containing heterocyclic groups play the role of pharmaco-effectivity.[5] It was assumed that the combination of DDB with substituted benzyl piperazines would produce some new compounds with activity against anti-HIV. Therefore, we designed and synthesized a class of novel 4,4'-dimethoxy-5,6,5',6'-dimethenedioxy biphenyls modified by substituted piperazines, and partly evaluated their anti-SIV activity.     

Synthesis of 5-Substituted-3-[(2’R,4’R)-4’-Hydroxy-2’-hydroxymethyltetrahydrofuran-4’-yl]-1,2,4-oxadiazoles and Their Epimers

The syntheses of 5-substituted-3-[( 2' R, 4' R)-4 ' -hydroxy-2 ' -hydroxymethyltetra-hydrofuran-4' -yl]D-1 ,2, 4-oxadiazoles and their epimers were accomplished with the aid of th construction of 1,2, 4-oxadiazoles by condensation of O-acylated cyanohydrins with hydroxylamine via intramolecular transacylation and subsequent cyclization.     

Acidichromism of indolinospirooxazines in isopropanol

1,3,3-tnmethyl-spiro[mdolino-2,3'-[2H]naphtho[2,1-b] [1,4]oxazine(SP1) and 1,3,3-trimen-thyl-9-methoxy-spiro[indolino2,3'-[2H]naphtho[2,1-b] [ 1,4]oxazine] (SP2) react with hydrochloric acid to form the complex SP HCl in isopropanol solution at room temperature The absorption maxima of these complexes are 440 and 463 nm respectively In acidic media,the opening form of spirooxazine can react with hydrochloric acid to form the complex PMC HCl via zwittenon form The absorption spectra of PMC HCl are obviously hypsochromic shifted compared with the reported spectra of the complex in neutral media In the mean time,the thermal stability of the complex is increased.The first order kinetics for the decoloration process of the acidichromic product of the opening form was determined and the lifetimes of these products are 180 and 200 s,respectively.