No abstract

The hypotheses that a firm's environmental performance has a positive impact on its financial performance and vice versa are statistically supported by Japanese data. However, this tendency for two-way positive interaction appears to be only a relatively recent phenomenon. The tendency for realizing the two-way interaction is not limited to the top-scoring firms in terms of both financial and environmental performance. On the contrary, this is also a trend that can be observed fairly generally. Obviously, when we consider only scores of those companies that published the relevant information in their environmental reports, and conduct the statistical causality test with such information as additional input to the pooled time-series and cross-section data of financial performance, the results become more strongly significant. From the recent experience of environmental policies in Japan, we infer that information-based environmental policy measures are effective to encourage the ongoing transition toward a more sustainable market economy.

The internal rotational barrier heights of biphenyl were calculated with the Dunning correlation consisted basis sets (up to cc-pVQZ, 960 basis functions) and the electron correlation correction by the second order Mo/ller-Plesset method (MP2). Although previous Hartree–Fock (HF) and MP2 calculations showed that the internal rotational barrier height at 0° (ΔE0) was substantially larger than that at 90° (ΔE90), our MP2/cc-pVQZ//MP2/6-31G* calculations showed that ΔE0 (2.28 kcal/mol) was close to ΔE90 (2.13 kcal/mol), which agreed with the estimation from experimental measurements. The calculations of benzene dimers suggested that the dispersion interaction increased the relative stability of the coplanar conformer. The basis sets employed in the previous calculations were not large enough to evaluate the attractive dispersion interaction. The underestimation of the stabilization of the coplanar conformer by the dispersion interaction would be one of the reasons for the overestimation of ΔE0 in the previous calculations.

Inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) represents a promising strategy for the discovery of a new generation of anticancer chemotherapeutics. Our synthetic efforts, beginning from the lead compound 2, were directed at improving antiproliferative activity against cancer cells as well as various drug properties. These efforts led to the discovery of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethylsulfoxide solvate (GSK1120212, JTP-74057 DMSO solvate; 1), a selective and highly potent MEK inhibitor with improved drug properties. We further confirmed that the antiproliferative activity correlates with cellular MEK inhibition and observed significant antitumor activity with daily oral dosing of 1 in a tumor xenograft model. These qualities led to the selection of 1 for clinical development.

The MP2 intermolecular interaction energies of the title complexes were calculated with the Dunning’s correlation consistent basis sets (cc-pVXZ, X=D, T, Q, and 5) and the interaction energies at the basis set limit were estimated. The second-order Mo/ller–Plesset (MP2) interaction energies greatly depend on the basis sets used, while the Hartree–Fock (HF) energies do not. Small basis sets considerably underestimate the attractive interaction. The coupled cluster single double triple [CCSD(T)] interaction energies are close to the MP2 ones. The expected CCSD(T) interaction energies of the H2O–MeOH, H2O–Me2O, H2O–H2CO, MeOH–MeOH, and HCOOH–HCOOH complexes at the basis set limit are −4.90, −5.51, −5.17, −5.45, and −13.93 kcal/mol, respectively, while the HF/cc-pV5Z energies are −3.15, −2.58, −3.60, −2.69, and −11.29 kcal/mol, respectively. The HF calculations greatly underestimate the attractive energies and fail to predict the order of the bonding energies in these complexes. These results show that a large basis set and the consideration of an appropriate electron correlation correction are essential to study interactions of hydrogen bonding complexes by ab initio molecular orbital calculation.

lminodiacetate complexes of lanthanide(ii1) ions (lutetium, europium, thulium and lanthanum), attached to the 5'-end of a 15-mer DNA, hydrolyse a 39-mer RNA selectively at the 3'-side of its 15-mersequence, which is complementary with the DNA.

Lanthanide(III) ions have shown enormous catalyses for the hydrolysis of the phosphodiester linkages in RNA, indicating their high potential for versatile applications to biotechnology and molecular biology. The activity monotonically increases with increasing atomic number in the lanthanide series, the last three ions (Tm3+, Yb3+, and Lu3+) being the most active. Non-lanthanide metal ions are virtually inactive. The pseudo first-order rate constant for the hydrolysis of adenylyl(3'-5')adenosine (ApA) by LuCl3 (5 mmol x dm(-3)) at pH 7.2 and 30 degrees C is 1.9 x 10(-1) min(-1) (the half-life is only 3.6 min), corresponding to 10(8)-fold acceleration. The product is an equimolar mixture of adenosine and its 2'- or 3'-monophosphate without any byproducts. The 2',3'-cyclic monophosphate of adenosine is not accumulated much in the reaction mixture. Lanthanide ions also efficiently hydrolyze oligoribonucleotides without a specific base-preference. In ApA hydrolysis by NdCl3 and GdCl3, the dependence of the hydrolysis rate on either the pH or concentration of the metal salt coincides fairly well with the corresponding profile of the equilibrium concentration of the bimetallic hydroxo-cluster [M2(OH)2]4+ (M=metal ion). Both the formation of the pentacoordinated intermediate and its decomposition are greatly promoted by lanthanide ions. A catalytic mechanism in which two metal ions (or their coordination water) in these tetracationic hydroxo-clusters show acid/base cooperation is proposed.

The cooperative action of multiple Cu(II) nuclear centers is shown to be effective and selective in the hydrolysis of 2'-5' and 3'-5' ribonucleotides. Reported herein is the specific catalysis by two trinuclear Cu(II) complexes of L3A and L3B. Pseudo first-order kinetic studies reveal that the L3A trinuclear Cu(II) complex effects hydrolysis of Up(2'-5')U with a rate constant of 28 x 10(-)(4) min(-)(1) and Up(3'-5')U with a rate constant of 0.5 x 10(-)(4) min(-)(1). The hydrolyses of Ap(3'-5')A and Ap(2'-5')A proceed with rate constants of 24 x 10(-)(4) min(-)(1) and 0.5 x 10(-)(4) min(-)(1) respectively. The L3A trinuclear Cu(II) complex demonstrates high specificity for Up(2'-5')U and Ap(3'-5')A. Similar studies with the more rigid L3B trinuclear Cu(II) complex shows no selectivity and yields lower rate constants for hydrolysis. The selectivity observed with the L3A ligand is attributed to the geometry of the ligand-bound diribonucleotide which ultimately dictates the proximity of the attacking hydroxyl and the phosphoester to a Cu(II) center for activation and subsequent hydrolysis.