A free energy calculation study of the effect of H-->F substitution on binding affinity in ligand-antibody interactions

Changes in binding affinity to catalytic antibody 6D9 of chloramphenicol phosphonate derivatives (CPDs) containing H or F were investigated by performing free energy calculations based on molecular dynamics simulations. We calculated the binding free energy, enthalpy, and entropy changes (DeltaDeltaG, DeltaDeltaH, and -TDeltaDeltaS) attributable to H-->F substitution by comparing results for CPDs containing a trifluoroacetylamino group (CPD-F) or an acetylamino group (CPD-H). The calculated DeltaDeltaG, DeltaDeltaH, and -TDeltaDeltaS values were -2.9, -6.3, and 3.5 kcal mol(-1) and close to experimental values observed for a series of similar ligands, chloramphenicol phosphonates with F and H (-1.4, -3.5, and 2.1 kcal mol(-1)). Therefore, CPD-F binds more strongly to 6D9 than does CPD-H. To clarify the origin of the large difference in DeltaDeltaG, we apportioned the calculated values of DeltaDeltaG and DeltaG for the associated and dissociated states into contributions from various atomic interactions. We found that the H-->F substitution increased the binding affinity mainly by decreasing the hydration free energy and not by increasing favorable interactions with the antibody. The decreased hydration free energy of the ligand was mainly due to unfavorable coulombic interactions between the trifluoroacetylamino group and solvent waters, which increased the free energy of the dissociated state (by about 3.7 kcal mol(-1)). Also, the trifluoroacetylamino group slightly increased the free energy level of the associated state (about 0.8 kcal mol(-1)) because favorable van der Waals interactions compensated for unfavorable coulombic interactions with antibody atoms. In addition, the enthalpy and entropy changes, DeltaDeltaH and -TDeltaDeltaS (computationally -6.3 and 3.5 kcal mol(-1)), originated mainly from a decrease in hydration free energy in the dissociated state. The CPD-F and CPD-H ligands had substantially different structures in the dissociated and complexed states.     

Highly (Z)-selective synthesis of beta-monosubstituted alpha,beta-unsaturated cyanides using the peterson reaction

[reaction: see text] The Peterson reaction between (t-BuO)Ph(2)SiCH(2)CN and various aldehydes furnishes the corresponding beta-monosubstituted alpha,beta-unsaturated cyanides with high Z selectivity (Z:E = 92:8 to >98:2).     

A New Family of Indoaniline-Derived Calix[4]arenes: Synthesis and Optical Recognition Properties as a Chromogenic Receptor(1)

A new family of indoaniline-derived calix[4]arenes has been synthesized for the purpose of developing a new chromogenic receptor. A condensing reaction of calix[4]arene (1) with 4-(diethylamino)-2-methylaniline hydrochloride (2) in the presence of an oxidizing agent under alkaline conditions affords mono- (3), 1,2-bis- (4), 1,3-bis- (5), and tetrakisindoaniline-derived (6) calix[4]arenes after careful column chromatography. Compound 3 is crystallized from a CHCl(3)-MeOH solution, and the crystal structure was determined by X-ray analysis. The crystal is monoclinic, space group P2(1)/n, Z = 4, a = 19.507(6) ?, b = 18.591(6) ?, c = 8.524(2) ?, beta = 94.69(2) degrees. The final R value for 2406 reflections of F(o) > 3sigma(F(o)) is 0.085. A unique intramolecular hydrogen-bonding network involving the carbonyl oxygen of indoaniline for 3 implied that the quinone carbonyl group as an acceptor of the chromophore can easily be subjected to an electrostatic interaction in the lower rim. Indeed, 1,3-bis(indoaniline)-derived 2,4-bis((ethoxycarbonyl)methoxy)calix[4]arene 7, prepared by the reaction of 5 with ethyl bromoacetate in the presence of NaH, is capable of undergoing an efficient ion-dipole interaction between the binding cation and the two quinone carbonyl groups of the chromophores, so that a selective Ca(2+)-induced pronounced color change (wavelength change > 100 nm) occurs with an association constant on the order of 10(6) in 99% EtOH, making 7 of potential use as an optical sensor for Ca(2+) detection. The IR and NMR studies have indicated that Ca(2+) is encapsulated in the cavity made by the distally located OCH(2)CO(2) groups on the lower rim of the cone-shaped calix[4]arene segment. Interestingly, however, the shape of the cavity in which Ca(2+) has been encapsulated does not have a C(2) axis of symmetry, as inferred from the (1)H-(1)H COSY experiment. On the other hand, 1,2-bis(indoaniline)-derived analogue 8 shows no response with metal ions, which can be interpreted to mean the absence of a cavity for encapsulation on the lower rim.     

Two-dimensional network formation of cardiac myocytes in agar microculture chip with 1480 nm infrared laser photo-thermal etching

We have developed a new method that enables agar microstructures to be used to cultivate cells and that allows cell network patterns to be controlled. The method makes use of non-contact three-dimensional photo-thermal etching with a 1480 nm infrared focused laser beam, which is strongly absorbed by water and agar gel, to form the shapes of agar microstructures. It allows microstructures to be easily formed in an agar layer within a few minutes, with cell-culture holes formed by the spot heating of a 100 mW laser and tunnels by the tracing of a 100 microm s(-1), 40 mW laser. We cultivated rat cardiac myocytes in adjacent microstructures and observed synchronized beating in them 90 min after they had made physical contact. Our results indicate that the system can make and use microstructures for cell-network cultivation in a minimal amount of time without any expensive microfabrication facilities or complicated procedures.     

Hydrogen Effect on Coke Removal and Catalytic Performance in Pre-Carburization and Methane Dehydro-Aromatization Reaction on Mo/HZSM-5

1. Introduction As an effective utilization of methane, the methane dehydro-aromatization was focused in the last decade [1-28]. Over the Mo/HZSM-5 bi- functional catalyst at high reaction temperature, methane can be converted into light aromatics (ben- zene and naphthalene) and hydrogen. Mo active species can activate the C—H bond of methane; and HZSM-5 supplies the acid sites for the oligomeriza- tion and cyclization of hydrocarbons to form aromat- ics, and suppresses the deeper condens…     

Polymerization of methyl methacrylate initiated by tri-n-butylborane–organic halide systems

The polymerization of methyl methacrylate (MMA) initiated by tri-n-butylborane (TBB) was studied in the presence of various organic halides (R′X). It was found that R′X accelerated the polymerization of MMA. Aliphatic halides were more effective than aromatic halides. Cocatalytic effects of butyl halides decreased in the order: n -BuI > n -BuBr > n -BuCl; n -BuBr ? sec-BuBr > i-BuBr > tert-BuBr. In the polymerization of MMA by TBB- n -BuI, the initial rate of polymerization was found to be proportional to the concentration of MMA and to the square root of the concentration of TBB-n-BuI. The apparent activation energy was 5.3 kcal/mole. From this and other results, it was assumed that the polymerization of MMA by this initiator system proceeds by a radical mechanism via a weak complex between TBB and R′X; alkyl radicals are formed by the interaction of R′X with TBB. The TBB–R′X system can initiate the polymerization of MMA and AN, but is ineffective in the polymerization of styrene.