Exceptionally slow kinetics of the intramolecular quadruplex formed by the Oxytricha telomeric repeat

We examined the stability and kinetics of folding of the Oxytricha telomeric repeat sequence (G4T4)4. Fluorescence melting experiments show that this intramolecular quadruplex, which is more stable in potassium- than sodium-containing buffers, shows considerable hysteresis between the melting and annealing profiles, even when heated at a rate of 0.05 degrees C min(-1). Quantitative analysis of this hysteresis, together with temperature-jump relaxation experiments show that the dissociation is exceptionally slow with a half-life of about 10 years at 37 degrees C in the presence of 50 mM K+. The association reaction has a half-life of a few seconds at 37 degrees C, but becomes slower at elevated temperatures consistent with the suggestion that association occurs by a nucleation-zipper mechanism.     

Kinetic and thermodynamic analysis of the hydrolytic ring-opening of the malondialdehyde-deoxyguanosine adduct, 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)- pyrimido[1,2-alpha]purin-10(3H)-one

3-(2'-Deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one (M1dG) is the major reaction product of deoxyguanosine with malondialdehyde or base propenals. M1dG undergoes hydrolytic ring-opening to N2-oxopropenyl-deoxyguanosine (N2OPdG) under basic conditions. We report that ring-opening of M1dG as a nucleoside or in oligonucleotides is a reversible second-order reaction with hydroxide ion. NMR and UV analysis revealed N2OPdG(-) to be the only product of M1dG ring-opening in basic solution. The rate constant for reaction of M1dG with hydroxide is 3.8 M(-1) s(-1), and the equilibrium constant is calculated to be 2.1 +/- 0.3 x 10(4) M(-1) at 25 degrees C. Equilibrium constants determined by spectroscopic analysis of the reaction end-point or by thermodynamic analysis of rate constants determined over a range of temperatures yielded a value 2.5 +/- 0.2 x 10(4) M(-1). Kinetic analysis of ring-opening of M1dG in oligonucleotides indicated the rate constant for ring-opening is decreased 10-fold compared to that in the nucleoside. Flanking purines or pyrimidines did not significantly alter the rate constants for ring-opening, but purines flanking M1dG enhanced the rate constant for the reverse reaction. A mechanism is proposed for ring-opening of M1dG under basic conditions and a role is proposed for duplex DNA in accelerating the rate of ring-opening of M1dG at neutral pH.     

Kinetics of hydrolysis of 8-(arylamino)-2'-deoxyguanosines

The 8-(arylamino)-2'-deoxyguanosines, or C-8 adducts, are the major adducts formed by reaction of N-arylnitrenium ions derived from carcinogenic and mutagenic amines with 2'-deoxyguanosine (d-G) and guanosine residues of DNA. The hydrolysis kinetics of three C-8 adducts 1a-c were determined by UV and HPLC methods at 20 degrees C under acidic, neutral, and mildly alkaline conditions. At pH < 2 the dominant hydrolysis process is spontaneous cleavage of the C-N bond of the doubly protonated substrate, 1H(2)(+2) (Scheme 2). The C-8 adducts are 2- to 5-fold more reactive than d-G under these conditions. At 3 < pH < 6 the hydrolysis kinetics are dominated by cleavage of the C-N bond of the monoprotonated nucleoside 1H(+). Under these conditions the hydrolysis kinetics are accelerated by 40- to 1300-fold over that of d-G. The rate increase appears to be caused by a combination of steric acceleration of C-N bond cleavage and a decrease in the ionization constant of 1H(+), K(a1), due to the electron-donating properties of the arylamino C-8 substituent. Under neutral pH conditions a slow (k(obs) approximately 10(-8) s(-1) to 5 x 10(-7) s(-1)) spontaneous cleavage of the C-N bond of the neutral nucleoside, 1, occurs that has not been previously reported for simple purine nucleosides. Finally, under mildly alkaline conditions a process consistent with spontaneous decomposition of the anion 1(-) or OH(-)-induced decomposition of 1 is observed. The latter process has been observed for other purine nucleosides, including the closely related 1d, and involves nucleophilic attack of OH(-) on C-8 to cleave the imidazole ring of the purine.     

Kinetics and mechanism of iron(III) dissociation from the dihydroxamate siderophores alcaligin and rhodotorulic acid

The kinetics and mechanism of siderophore ligand dissociation from their fully chelated Fe(III) complexes is described for the highly preorganized cyclic tetradentate alcaligin and random linear tetradentate rhodotorulic acid in aqueous solution at 25 degrees C (Fe2L3 + 6H+ reversible 2 Fe3+ aq + 3 H2L). At siderophore:Fe(III) ratios where Fe(III) is hexacoordinated, kinetic data for the H(+)-driven ligand dissociation from the Fe2L3 species is consistent with a singly ligand bridged structure for both the alcaligin and rhodotorulic acid complexes. Proton-driven ligand dissociation is found to proceed via parallel reaction paths for rhodotorulic acid, in contrast with the single path previously observed for the linear trihydroxamate siderophore ferrioxamine B. Parallel paths are also available for ligand dissociation from Fe2(alcaligin)3, although the efficiency of one path is greatly diminished and dissociation of the bis coordinated complex Fe(alcaligin)(OH2)2+ is extremely slow (k = 10(-5) M-1 s-1) due to the high degree of preorganization in the alcaligin siderophore. Mechanistic interpretations were further confirmed by investigating the kinetics of ligand dissociation from the ternary complexes Fe(alcaligin)(L) in aqueous acid where L = N-methylacetohydroxamic acid and glycine hydroxamic acid. The existence of multiple ligand dissociation paths is discussed in the context of siderophore mediated microbial iron transport.     

The Reversible Insertion Reaction of Carbon Dioxide with the W(CO)(5)OH(-) Anion. Isolation and Characterization of the Resulting Bicarbonate Complex [PPN][W(CO)(5)O(2)COH

[Et(4)N][W(CO)(5)OH] (1) and [PPN][W(CO)(5)O(2)COH] (2) have been synthesized and characterized by (1)H and (13)C NMR and IR spectroscopies, and the X-ray crystal structure of 2 has been determined. Complex 2 crystallizes in the triclinic space group P&onemacr; with unit cell parameters a = 12.208(2) ?, b = 13.497(2) ?, c = 13.681(2) ?, alpha = 101.06(2) degrees, beta = 114.76(1) degrees, gamma = 98.45(2) degrees, V = 1942.6(5) ?(3), and Z = 2. The structure of the anion of complex 2 consists of a central W(0) bound to five carbonyl ligands, and the coordination around the metal is completed by a monodentate bound bicarbonate ligand located 2.19(1) ? away from the metal center. In the solid state, two anions are hydrogen bonded to one another via the bicarbonate ligands in the unit cell. Complex 1 inserts CO(2), COS, or CS(2) to rapidly afford the corresponding bicarbonate or thiocarbonate complexes. The lower limit for the rate constant for the carboxylation of complex 1 has been determined to be 4.2 x 10(-)(4) M(-)(1) s(-)(1) at -70.2 degrees C, and the lower limit for the rate constant for the decarboxylation of complex 2 has been found to be 2.5 x 10(-)(3) s(-)(1) at 20.0 degrees C. In addition, the rate constant for the decarbonylation of 2 was determined to be 7.60 x 10(-)(3) s(-)(1) at 36.0 degrees C, a value which is somewhat faster than anticipated on the basis of analogous data for a large variety of W(CO)(5)O(2)CR(-) derivatives. This is attributed to a diminution of the electron-withdrawing ability of the OH substituent in O(2)COH as a result of hydrogen bonding to solvent. Nevertheless, it is clear that the rate of decarboxylation of the anion from complex 2 is faster than the rate of CO dissociation. Concomitantly, carboxylation of complex 1 is faster than CO dissociation, since the W(CO)(5)OH(-) is inert toward (13)CO exchange on the time scale of carboxylation at -70.2 degrees C.     

Kinetics and mechanism of the general-acid-catalyzed ring-closure of the malondialdehyde-DNA adduct, N2-(3-oxo-1-propenyl)deoxyguanosine (N2OPdG-), to 3-(2'-Deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin- 10(3H)-one (M1dG)

3-(2'-Deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one (M1dG) is the major product of the reaction of deoxyguanosine with malondialdehyde (MDA). M1dG blocks replication by DNA polymerases in vitro and is mutagenic in vivo. M1dG reacts with hydroxide to form the N2-(3-oxo-1-propenyl)deoxyguanosine anion (N2OPdG-). This reaction is pH-dependent and reverses under neutral and acidic conditions to form M1dG. Here we describe the kinetics and mechanism of the ring-closure reaction in both the nucleoside and oligonucleotides. Kinetic analysis of absorbance and fluorescence changes demonstrates that ring-closure is biphasic, leading to the rapid formation of an intermediate that slowly converts to M1dG in a general-acid-catalyzed reaction. The dependence of the rate of the rapid phase on pH reveals the pKa for protonated N2OPdG is 6.9. One-dimensional 1H NMR and DQF-COSY experiments identified two distinct intermediates, N2OPdG-H and 8-hydroxy-6,7-propenodeoxyguanosine (HO-Prene-dG), that are formed upon acidification of N2OPdG-. Characterization of ring-closure in single-stranded and in melted duplex oligonucleotides shows M1dG formation is also acid-catalyzed in single-stranded oligonucleotides and that the denaturation of an oligonucleotide duplex enhances ring-closure. This work details the complexity of ring-closure in the nucleoside and oligonucleotides and provides new insight into the role of duplex DNA in catalyzing ring-opening and ring-closing of M1dG and N2OPdG.     

DNA binding and cytotoxicity of ruthenium(II) and rhenium(I) complexes of 2-amino-4-phenylamino-6-(2-pyridyl)-1,3,5-triazine

[Ru(tBu2bpy)2(2-appt)](PF6)2 [1.(PF6)2, tBu2bpy = 4,4'-di-tert-butyl-2,2'-bipyridine, 2-appt = 2-amino-4-phenylamino-6-(2-pyridyl)-1,3,5-triazine] and [Re(CO)3(2-appt)Cl] (2) were prepared and characterized by X-ray crystal analysis. The binding of 1.(PF6)2 and 2 to calf thymus DNA (ct DNA) led to increases in the DNA melting temperature (Delta Tm = +12 degrees C), modest hypochromism (29% and 5% of the absorption bands at lambda max = 450 and 376 nm, respectively), and insignificant shifts in the absorption maxima. The binding constants of 1.(PF6)2 and 2 with ct DNA, as determined by absorption titration, are (8.9 +/- 0.5) x 104 and (3.6 +/- 0.1) x 104 dm3 mol-1, respectively. UV-vis absorption titration, DNA melting studies, and competition dialysis using synthetic oligonucleotides [poly(dA-dT)2 and poly(dG-dC)2] revealed that 1.(PF6)2 and 2 exhibit a binding preference for AT sequences. A modeling study on the interaction between 1 or 2 and B-DNA revealed that the minor groove is the most favored binding site and an extensive hydrogen-bonding network is formed. As determined by MTT assays, 1.(PF6)2 and 2 exhibited moderate cytotoxicities toward several human cancer cell lines (KB-3-1, HepG2, and HeLa), as well as a multi-drug-resistant cancer cell line (KB-V-1). According to confocal microscopic and flow cytometric studies, 1.(PF6)2 and 2 induced apoptosis (50-60%) in cancer cells with <5% necrosis detected.     

Kinetics of Dissociation of tris-{3-(2-pyridyl)-5,6-bis(2-furyl)-1,2,4-triazine}iron(II)

The kinetics of base hydrolysis of the low-spin iron(II)-diimine complex [Fe(fertri)₃]²⁺, where fertri=3-(2-pyridyl)-5,6-bis(2-furyl)-1,2,4-triazine, as a function of hydroxide concentration, solvent composition (water; aqueous MeOH), and pressure are reported. Rate constants are also reported for dissociation of the [Fe(fertri)₃]²⁺ cation in 50–64% MeOH, determined from replacement of the fertri ligands by 1,10-phenanthroline. The reactivity of this fertri complex is compared with reactivities of a selection of other iron(II)-diimine complexes and, where possible, their ligand-sulfonated derivatives. The activation volume for base hydrolysis of [Fe(fertri)₃]²⁺ is +10.7 cm³ mol⁻¹, in 40% MeOH.     

Understanding the role of the sulfide redox couple (S2-/S(n)2-) in quantum dot-sensitized solar cells

The presence of sulfide/polysulfide redox couple is crucial in achieving stability of metal chalcogenide (e.g., CdS and CdSe)-based quantum dot-sensitized solar cells (QDSC). However, the interfacial charge transfer processes play a pivotal role in dictating the net photoconversion efficiency. We present here kinetics of hole transfer, characterization of the intermediates involved in the hole oxidation of sulfide ion, and the back electron transfer between sulfide radical and electrons injected into TiO(2) nanoparticles. The kinetic rate constant (10(7)-10(9) s(-1)) for the hole transfer obtained from the emission lifetime measurements suggests slow hole scavenging from CdSe by S(2-) is one of the limiting factors in attaining high overall efficiency. The presence of the oxidized couple, by addition of S or Se to the electrolyte, increases the photocurrent, but it also enhances the rate of back electron transfer.     

Initial oxidation and hydroxylation of the Ge(100)-2 x 1 surface by water and hydrogen peroxide

We use density functional theory to investigate the surface chemistry of initial oxidation and hydroxylation of the Ge(100)-2 x 1 surface by water and hydrogen peroxide. Comparison of the reaction of water on the Si(100)-2 x 1 and Ge(100)-2 x 1 surfaces shows that the kinetics of oxidation of the Ge(100)-2 x 1 surface with water is slower. Our calculations also show that oxidation products on the Ge(100)-2 x 1 surface are less thermodynamically stable than on Si. We also investigate two competing dissociation reactions of H2O2 on the Ge(100)-2 x 1 surface. We find that dissociative adsorption via cleavage of the OH bond is less exothermic than OO dissociation. Furthermore, interdimer OO dissociation has a lower activation barrier than interdimer or intradimer OH dissociation, although interdimer dissociation products are found to be less stable compared than those formed from intradimer dissociation reactions. Finally, we find that the oxidation products formed from hydrogen peroxide are more stable than those formed from water.     

Kinetic and computational study of dissociative substitution and phosphine exchange at tetrahedrally distorted cis-Pt(SiMePh2)2(PMe2Ph)2

The substitution kinetics of Me2PhP in cis-Pt(SiMePh2)2(PMe2Ph)2 (1) by the chelating ligand bis(diphenylphosphino)ethane has been followed at 25.0 degrees C in dichloromethane by stopped-flow spectrophotometry. Addition of the leaving ligand causes mass-law retardation compatible with a dissociative process via a three-coordinate transition state or intermediate. Exchange of Me2PhP in 1 has been studied by variable-temperature magnetization transfer 1H NMR in toluene-d8, giving kex326 = 1.76 +/- 0.12 s-1, delta H++ = 117.8 +/- 2.1 kJ mol-1, and delta S++ = 120 +/- 7 J K-1 mol-1. An exchange rate constant independent of the concentrations of free phosphine, a strongly positive delta S++, and nearly equal exchange and ligand dissociation rate constants also support a dissociative process. Density functional theory (DFT) calculations for a dissociative process give an estimate for the Pt-P bond energy of 98 kJ mol-1 for R = R' = Me, which is in reasonable agreement with the experimental activation energy given the differences between the substituents used in the calculation and those employed experimentally. DFT calculations on cis-Pt(PR3)2(SiR'3)2 (R = H, CH3; R' = H, CH3) are consistent with the experimental molecular structure and show that methyl substituents on the Si donors are sufficient to induce the observed tetrahedral twist. The optimized Si-Pt-Si angle in cis-Pt(SiH3)2(PH3)2 is not significantly altered by changing the P-Pt-P angle from its equilibrium value of 104 degrees to 80 degrees or 120 degrees. The origin of the tetrahedral twist is therefore not steric but electronic. The Si-Pt-Si angle is consistently less than 90 degrees, but the Si-Si distance is still too long to support an incipient reductive elimination reaction with its attendant Si-Si bonding interaction. Instead, it appears that four tertiary ligands introduce a steric strain which can be decreased by a twist of two of the ligands out of the plane; this twist is only possible when two strong sigma donors are cis to each other, causing a change in the metal's hybridization.     

Kinetics and mechanism of ring transformation of S-[1-(4-methoxyphenyl)pyrrolidin-2-on-3-yl]isothiuronium bromide to 2-methylimino-5-[2-(4-methoxyphenylamino)ethyl]thiazolidin-4-one

The kinetics and mechanism of transformation reaction of S-[1-(4- methoxyphenyl)pyrrolidin-2-one-3-yl]-N-methyl-isothiuronium bromide into 2-methylimino-5-[2-(4-methoxyphenylamino) ethyl)]thiazolidin-4-one have been studied in aqueous solutions of amine buffers (pH 8.1-11.5) and sodium hydroxide solutions (0.005-0.5 mol l-1) at 25 degrees C and at I = 1 mol l-1 at pseudo-first-order reaction conditions. The kinetics observed shows that the transformation reaction is subject to general base, general acid, and hydroxide-ion catalyses. The rate-limiting step of transformation is the splitting-off a proton from the tetrahedral intermediate In. The value of pKa for S-[1-(4-methoxyphenyl)- pyrrolidin-2-one-3-yl]-N-methylisothiuronium bromide has been determined from the kinetic data (pKa = 8.75 +/- 0.10) and by potentiometric titration (pKa = 8.90 +/- 0.05). With increasing pKa value of the acid buffer component, the value of Br?nsted coefficient beta gradually decreases from about 0.7 to almost zero. The value of pKa approximately 10 for the intermediate to base-catalysed transformation has been found from this dependence. In the N-methylpyrrolidine and triethylamine buffers, the rate-limiting step of transformation is changed into ring opening of In-, and the general-base-catalysed reaction changes into a specific-base-catalysed one.     

Synthesis and characterization of the SO(2)N(3)(-), (SO(2))(2)N(3)(-), and SO(3)N(3)(-) anions

SO(2) solutions of azide anions are bright yellow, and their Raman spectra indicate the presence of covalently bound azide. Removal of the solvent at -64 degrees C from CsN(3) or N(CH(3))(4)N(3) solutions produces yellow (SO(2))(2)N(3)(-) salts. Above -64 degrees C, these salts lose 1 mol of SO(2), resulting in white SO(2)N(3)(-) salts that are marginally stable at room temperature and thermally decompose to the corresponding azides and SO(2). These anions were characterized by vibrational and (14)N NMR spectroscopy and theoretical calculations. Slow loss of the solvent by diffusion through the walls of a sealed Teflon tube containing a sample of CsSO(2)N(3) in SO(2) resulted in white and yellowish single crystals that were identified by X-ray diffraction as CsSO(2)N(3).CsSO(3)N(3) with a = 9.542(2) A, b = 6.2189(14) A, c = 10.342(2) A, and beta = 114.958(4) degrees in the monoclinic space group P2(1)/m, Z = 2, and Cs(2)S(2)O(5).Cs(2)S(2)O(7).SO(2), respectively. Pure CsSO(3)N(3) was also prepared and characterized by vibrational spectroscopy. The S-N bond in SO(2)N(3)(-) is much weaker than that in SO(3)N(3)(-), resulting in decreased thermal stability, an increase in the S-N bond distance by 0.23 A, and an increased tendency to undergo rotational disorder. This marked difference is due to SO(3) being a much stronger Lewis acid (pF(-) value of 7.83) than SO(2) (pF(-) value of 3.99), thus forming a stronger S-N bond with the Lewis base N(3)(-). The geometry of the free gaseous SO(2)N(3)(-) anion was calculated at the RHF, MP2, B3LYP, and CCSD(T) levels. The results show that only the correlated methods correctly reproduce the experimentally observed orientation of the SO(2) group.     

Kinetic Investigation of Homogeneous H(2)-D(2) Equilibration Catalyzed by Pt-Au Cluster Compounds. Characterization of the Cluster [(H)Pt(AuPPh(3))(9)](NO(3))(2)

The new Pt-Au hydrido cluster compound [(H)Pt(AuPPh(3))(9)](NO(3))(2) (3) has been synthesized and characterized by NMR, FABMS, and single-crystal X-ray diffraction [triclinic, P&onemacr;, a = 17.0452(1) ?, b = 17.4045(2) ?, c = 55.2353(1) ?, alpha = 89.891(1) degrees, beta = 85.287(1) degrees, gamma = 75.173(1) degrees, V = 15784.0(2) ?(3), Z = 4 (two molecules in asymmetric unit), residual R = 0.089 for 45 929 observed reflections and 3367 variables, Mo Kalpha radiation]. The Pt(AuP)(9) core geometry is a distorted icosahedron with three vertices vacant. The Pt-Au, Au-Au, and Au-P distances are within the normal ranges observed in other Pt-Au clusters. This cluster is a catalyst for H(2)-D(2) equilibration in homogeneous solution phase and has been used in a general mechanistic study of this reaction catalyzed by Pt-Au clusters. We previously proposed that a key step in the mechanism for catalytic H(2)-D(2) equilibration is the dissociation of a PPh(3) ligand to give a cluster with an open Au site for bonding of H(2) or D(2). This was based on qualitative observations that PPh(3) inhibited the rate of HD production with [Pt(AuPPh(3))(8)](NO(3))(2) (1) as catalyst. In order to test this hypothesis, phosphine inhibition (on the rate of HD production) and phosphine ligand exchange kinetic experiments were carried out with [(H)(PPh(3))Pt(AuPPh(3))(7)](NO(3))(2) (2) and 3. In this paper we show that the rate constant for phosphine dissociation determined from the PPh(3) inhibition rate study of H(2)-D(2) equilibration with cluster 2 is nearly identical to the rate constant for dissociative phosphine ligand exchange. The slower rate for H(2)-D(2) equilibration observed with 3 compared with 2 (5.5 x 10(-3) vs 7.7 x 10(-2) turnover s(-1)) is explained by its smaller rate constant for phosphine dissociation (2.8 x 10(-5) vs 2.9 x 10(-4) s(-1)). The fact that clusters 2 and 3 show similar kinetic behaviors suggests that the PPh(3) dissociation step in the catalytic H(2)-D(2) equilibration is general for 18-electron hydrido Pt-AuPPh(3) clusters.     

Radical nucleophilic substitution of 2-(4-halophenyl)-2-methyl-1-chloropropane with enolate ions of ketones

The photoinitiated reaction of 2-(4-halophenyl)-2-methyl-1-chloropropane 2a,b (halogen=Br, I, respectively) with the anions of pinacolone (3a) and acetophenone (3b) either in DMSO or in liquid ammonia are reported. In DMSO, the main reaction is the SRN1 nucleophilic substitution at the aromatic (Csp2-halogen) center with substitution or reduction at the aliphatic (Csp3-Cl) one. In liquid ammonia, the main reaction is substitution at the aromatic C-halogen site. This difference in product distribution is ascribed to modifications in the rate constant of Csp3-Cl dissociation of the radical anions proposed as intermediates in going from DMSO (rt) to liquid NH3 (-33 degrees C).     

Kinetics of the reactions between [S(2)MoS(2)Cu(SC(6)H(4)R-4)](2-)(R = MeO, H, Cl or NO(2)) and CN(-): substitution mechanism at a 3-coordinate Cu(I) site

The kinetics of the reaction between [S(2)MoS(2)Cu(SC(6)H(4)R-4)](2-)(R = MeO, H, Cl or NO(2)) and CN(-) to form [S(2)MoS(2)CuCN](2-) have been studied in MeCN using stopped-flow spectrophotometry. In all cases, the rate law is of the form, Rate ={k+k(2)(R)[CN(-)]}[S(2)MoS(2)Cu(SC(6)H(4)R-4)(2-)]. It is proposed that both k and k correspond to associative substitution mechanisms. The k pathway involves attack by CN(-) at the copper site followed by dissociation of the thiolate. The k pathway involves attack of the solvent (MeCN) at the copper site, followed by dissociation of the thiolate to form [S(2)MoS(2)Cu(NCMe)](-). Subsequent rapid substitution of the coordinated solvent by cyanide produces [S(2)MoS(2)CuCN](2-). The evidence that both the k and k pathways involve associative mechanisms are: (i) the 4-R-substituent on the thiolate ligand has a similar effect on both k and k, with electron-withdrawing 4-R-substituents facilitating substitution; (ii) both the k and k pathways are associated with similar activation parameters (for k(1)(H): DeltaH++ = 5.5 +/- 0.5 kcal mol(-1), DeltaS++ = -23.9 +/- 2.0 cal deg(-1) mol(-1); for k(2)(H): DeltaH++ = 2.3 +/- 0.5 kcal mol(-1), DeltaS++ = - 23.9 +/- 2.0 cal deg(-1) mol(-1)) and (iii) addition of C(6)H(5)S(-) results in a similar increase in both k and k.     

Multifunctional Ligands. Phosphinimine-Substituted Cyanofluoroaromatics Including X-ray Molecular Structures of Three Representative Ligands 4,6-(CN)(2)C(6)F(2)-1,3-(N=PPh(3))(2), 4,6-(CN)(2)C(6)F(2)-1,3-(N=PPh(2)Me)(2) and 4,6-(CN)(2)C(6)F(2)-1-(N=PPh(3))-3-(N=PPh(2)Me). Formation of Rhodium(I) Complexes

Reaction of 1,3-dicyanotetrafluorobenzene with 2 equiv of (trimethylsilyl)iminophosphoranes gave the disubstituted derivatives 4,6-(CN)(2)C(6)F(2)-1,3-AB: 1, A = B = (N=PPh(3)); 2, A = B = (N=PPh(2)Me); and 3, A = (N=PPh(3)), B = (N=PPh(2)Me). Monosubstituted compounds of the type 2,4-(CN)(2)C(6)F(3)-1-A; notably 4, A = (N=PPh(3)), and 5, A = (N=PPh(2)Me), were readily obtained by reaction of 1 molar equiv of the silylated iminophosphorane with the cyanofluoro aromatic. Substitution of the fluorine para to the CN group(s) occurs in all cases. Reactions of 1,2- and 1,4-dicyanotetrafluorobenzene with (trimethylsilyl)iminophosphoranes gave only monosubstituted derivatives 3,4-(CN)(2)C(6)F(3)-1-A (6, A = (N=PPh(3)), and 7, A = (N=PPh(2)Me)) and 2,5-(CN)(2)C(6)F(3)-1-A (8, A = (N=PPh(3)), and 9, A = (N=PPh(2)Me)), respectively, as the result of electronic deactivation of the second substitutional point. 1, 4,6-(CN)(2)C(6)F(2)-1,3-(N=PPh(3)), 2, 4,6-(CN)(2)C(6)F(2)-1,3-(N=PPh(2)Me)(2), and 3, 4,6-(CN)(2)C(6)F(2)-1-(N=PPh(3))-3-(N=PPh(2)Me) have been structurally characterized. For 1 (at 21 degrees C), monoclinic, C2/(c) (No. 15), a = 15.289(2) ?, b = 10.196(1) ?, c = 23.491(6) ?, beta = 91.63(2) degrees, V = 3660(2) ?(3), and Z = 4. The P=N bond length is 1.579(2) ? and the P(V)-N-C(phenyl) angle is 134.0(2) degrees. For 2, (at 21 degrees C) monoclinic, C2/(c) (No. 15), a = 18.694(2) ?, b = 8.576(1) ?, c = 40.084(4) ?, beta = 94.00(1) degrees, V = 6411(2) ?(3), and Z = 8. The P(1)=N(1) bond length is 1.570(4) ?, the P(2)=N(2) bond length is 1.589(3) ?, the P(1)-N(1)-C(14) angle is 131.6(3) degrees, and the P(2)-N(2)-C(16) angle is 131.3(3) degrees. For 3, (at -80 degrees C) monoclinic, P2(1)/c (No. 14), a = 9.210(1) ?, b = 18.113(2) ?, c = 20.015(2) ?, beta = 100.07(1) degrees, V = 3287(2) ?(3), and Z = 4. The P(1)=N(1) bond length (PPh(3) group) is 1.567(4) ?, the P(2)=N(2) bond length (PPh(2)Me group) is 1.581(5) ?, the P(1)-N(1)-C(1) angle is 140.4(4) degrees, and the P(2)-N(2)-C(3) angle is 129.4(4) degrees. These new multifunctional chelating ligands readily react with [Rh(cod)Cl](2) and AgClO(4) to give cationic Rh(I) complexes in which the imine and/or the nitrile groups are coordinated to the Rh center.     

Formation and dissociation kinetics of Cu(II) and Ni(II) complexes with N2S2-macrocycles

The kinetics of the formation and dissociation of the Cu(2+) and Ni(2+) complexes with a series of N(2)S(2) macrocycles, in which the ring size and the geometry of the arrangement of the donor groups have been varied, have been measured at 25 [degree]C and I= 0.5 (KNO(3)). Both the deprotonated (L) and the monoprotonated (LH(+)) form of the ligands are reactive species in the formation step. In their deprotonated form, first bond formation, in some cases supported by an ICB effect, is rate determining, independently of the ring size. In the monoprotonated form, we find slower rates, due to the charge repulsion and/or conformation changes induced by hydrogen bonds. In contrast the mechanism of the dissociation is very dependent on the ring size. The complexes with the smaller rings react as flexible open-chain ligands directly with H(+). In contrast, the complexes with the larger rings react in a similar way as rigid ligands: first the metal amine bond slowly dissociates so that the free electron pair of the amine can take the "out conformation" and then it is protonated. The 14-membered macrocycle L(3) forms complexes in which the metal ions are ideally coordinated so that their dissociation becomes extremely slow.     

2'-O-[2-(guanidinium)ethyl]-modified oligonucleotides: stabilizing effect on duplex and triplex structures

[structure: see text] Oligonucleotides with a novel 2'-O-[2-(guanidinium)ethyl] (2'-O-GE) modification have been synthesized using a novel protecting group strategy for the guanidinium group. This modification enhances the binding affinity of oligonucleotides to RNA as well as duplex DNA (DeltaT(m) 3.2 degrees C per modification). The 2'-O-GE modified oligonucleotides exhibited exceptional resistance to nuclease degradation. The crystal structure of a palindromic duplex formed by a DNA oligonucleotide with a single 2'-O-GE modification was solved at 1.16 A resolution.     

Preparation and characterization of two crystalline forms of 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrroli dinyl]benzamide (TKS159)

For 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrrolid inyl]benzamide (TKS159), two polymorphs, forms alpha and beta, were prepared and characterized by means of X-ray powder diffractometry, thermal analysis, infrared spectroscopy and 13C-NMR spectroscopy, both in the solution and solid phases. The X-ray powder diffraction analysis gave different patterns for forms alpha and beta. In the thermogravimetry and differential thermal analysis profiles, form beta exhibited characteristic endo- and exothermic peaks at 112.7 degrees C and 116.2 degrees C, respectively, due to the partial melting-induced phase transition to form alpha without accompanying weight loss, and these were followed by an additional endothermic peak at 138.2 degrees C due to fusion. For form alpha, only an endothermic peak at 137.8 degrees C due to fusion was observed. The IR spectroscopic analyses of forms alpha and beta gave different absorption bands assigned to N-H and O-H stretching, N-H bending, and C=O stretching vibrations. From the data obtained by thermal analysis, form alpha was shown to be thermodynamically more stable than form beta.