Synthesis of a 2-Methyl-4-sulfanilamido-s-triazine derivative

An attempt to obtain 2-methyl-4-sulfanilamido-s-triazine (XXI) by condensation of 2-amino-4-methyl-s-triazine (II) with p-acetamidobenzenesulfonyl chloride (III) in pyridine and in benzene containing trimethylamine gave instead the unexpected products, guanidine N-acetylsulfanilate (IV) (after hydrolysis) and N¹,N¹-dimethylsulfanilamide (V), respectively. On the other hand, 2-methyl-4-methylthio-6-sulfanilamido-s-triazine (XIX) was obtained from 4,6-dimethylthio-s-triazine (XVII), but the reduction of XIX with Raney nickel in aqueous sodium hydroxide solution also gave an unexpected compound, sulfaguanidine (XX).     

Understanding rubredoxin redox sites by density functional theory studies of analogues

Determining the redox energetics of redox site analogues of metalloproteins is essential in unraveling the various contributions to electron transfer properties of these proteins. Since studies of the [4Fe-4S] analogues show that the energies are dependent on the ligand dihedral angles, broken symmetry density functional theory (BS-DFT) with the B3LYP functional and double-ζ basis sets calculations of optimized geometries and electron detachment energies of [1Fe] rubredoxin analogues are compared to crystal structures and gas-phase photoelectron spectroscopy data, respectively, for [Fe(SCH(3))(4)](0/1-/2-), [Fe(S(2)-o-xyl)(2)](0/1-/2-), and Na(+)[Fe(S(2)-o-xyl)(2)](1-/2-) in different conformations. In particular, the study of Na(+)[Fe(S(2)-o-xyl)(2)](1-/2-) is the only direct comparison of calculated and experimental gas phase detachment energies for the 1-/2- couple found in the rubredoxins. These results show that variations in the inner sphere energetics by up to ～0.4 eV can be caused by differences in the ligand dihedral angles in either or both redox states. Moreover, these results indicate that the protein stabilizes the conformation that favors reduction. In addition, the free energies and reorganization energies of oxidation and reduction as well as electrostatic potential charges are calculated, which can be used as estimates in continuum electrostatic calculations of electron transfer properties of [1Fe] proteins.     

Soft sticky dipole-quadrupole-octupole potential energy function for liquid water: an approximate moment expansion

A new, efficient potential energy function for liquid water is presented here. The new model, which is referred here as the soft sticky dipole-quadrupole-octupole (SSDQO) model, describes a water molecule as a Lennard-Jones sphere with point dipole, quadrupole, and octupole moments. It is a single-point model and resembles the hard-sphere sticky dipole potential model for water by Bratko et al. [J. Chem. Phys. 83, 6367 (1985)] and the soft sticky dipole model by Ichiye and Liu [J. Phys. Chem. 100, 2723 (1996)] except now the sticky potential consists of an approximate moment expansion for the dimer interaction potential, which is much faster than the true moment expansion. The object here is to demonstrate that the SSDQO potential energy function can accurately mimic the potential energy function of a multipoint model using the moments of that model. First, the SSDQO potential energy function using the dipole, quadruple, and octupole moments from SPC/E, TIP3P, or TIP5P is shown to reproduce the dimer potential energy functions of the respective multipoint model. In addition, in Monte Carlo simulations of the pure liquid at room temperature, SSDQO reproduces radial distribution functions of the respective model. However, the Monte Carlo simulations using the SSDQO model are about three times faster than those using the three-point models and the long-range interactions decay faster for SSDQO (1/r(3) and faster) than for multipoint models (1/r). Moreover, the contribution of each moment to the energetics and other properties can be determined. Overall, the simplicity, efficiency, and accuracy of the SSDQO potential energy function make it potentially very useful for studies of aqueous solvation by computer simulations.     

A rheology model of high damping rubber bearings for seismic analysis: Identification of nonlinear viscosity

The mechanical behavior of high damping rubber bearings (HDRBs) is investigated under horizontal cyclic shear deformation with a constant vertical compressive load. On the basis of experimental observations, an elasto-viscoplastic rheology model of HDRBs for seismic analysis is developed. In this model, the Maxwell model is extended by adding a nonlinear elastic spring and an elasto-plastic model (spring-slider) in parallel. In order to identify constitutive relations of each element in the rheology model, an experimental scheme comprised of three types of tests, namely a cyclic shear (CS) test, a multi-step relaxation (MSR) test, and a simple relaxation (SR) test, are carried out at room temperature. HDRB specimens with the standard ISO geometry and three different high damping rubber materials are employed in these tests. A nonlinear viscosity law of the dashpot in the Maxwell model is deduced from the experimental scheme, and incorporated into the rheology model to reproduce the nonlinear rate dependent behavior of HDRBs. Finally, numerical simulation results for sinusoidal loading are presented to illustrate capability of the proposed rheology model in reproducing the mechanical behavior of HDRBs.     

Reduction potential calculations of the Fe–S clusters in Thermus thermophilus respiratory complex I

Respiratory complex I facilitates electron transfer from NADH to quinone over ~95 Å through a chain of seven iron–sulfur (Fe–S) clusters in the respiratory chain. In this study, the reduction potentials of the Fe–S clusters in Thermus thermophilus complex I are calculated using a Density Functional Theory + Poisson–Boltzmann method. Our results indicate that the reduction potentials are influenced by a variety of factors including the clusters being deeply buried in the complex and the protonation state of buried ionizable residues. In addition, as several of the ionizable side chains have predicted pK_a values near pH 7, relatively small structural fluctuations could lead to significant (0.2 V) shifts in the reduction potential of several of the Fe–S clusters, suggesting a dynamic mechanism for electron transfer. Moreover, the method used here is a useful computational tool to study other questions about complex I. © 2019 Wiley Periodicals, Inc.     

Linear concentration dependence of vibrational width and vibrational dephasing paths in aqueous nitrate solutions

A theoretical model of vibrational dephasing of Raman active ions in aqueous electrolyte solutions is presented in which a probe ion is coupled to the bath by direct ion-solvent and ion-ion interactions. Expression for the vibrational width in terms of concentrations and efficiencies of the vibrational frequency modulation by ion-perturber interactions is given in the fast modulation scheme. The observed linear concentration dependence of the vibrational dephasing width of the v ₁(A'₁) mode of NO₃ ^- in aqueous solutions is reasonably well explained from this model, and efficiencies of the dephasing paths through NO₃ ^--water hydrogen bonding interaction and contact NO₃ ^--cation pair formation interaction are estimated. Anions in the solution give only a secondary effect to nitrate vibrational dephasing because of interionic repulsive forces.     

Direct measurement of the hydrogen-bonding effect on the intrinsic redox potentials of [4Fe-4S] cubane complexes

To probe how H-bonding effects the redox potential changes in Fe-S proteins, we produced and studied a series of gaseous cubane-type analogue complexes, [Fe(4)S(4)(SEt)(3)(SC(n)H(2n+1))](2-) and [Fe(4)S(4)(SEt)(3)(SC(n)H(2n)OH)](2-) (n = 4, 6, 11; Et = C(2)H(5)). Intrinsic redox potentials for the [Fe(4)S(4)](2+/3+) redox couple involved in these complexes were measured by photoelectron spectroscopy. The oxidation energies from [Fe(4)S(4)(SEt)(3)(SC(n)H(2n)OH)](2-) to [Fe(4)S(4)(SEt)(3)(SC(n)H(2n)OH)](-) were determined directly from the photoelectron spectra to be approximately 130 meV higher than those for the corresponding [Fe(4)S(4)(SEt)(3)(SC(n)H(2n+1))](2-) systems, because of the OH...S hydrogen bond in the former. Preliminary Monte Carlo and density functional calculations showed that the H-bonding takes place between the -OH group and the S on the terminal ligand in [Fe(4)S(4)(SEt)(3)(SC(6)H(12)OH)](2-). The current data provide a direct experimental measure of a net H-bonding effect on the redox potential of [Fe(4)S(4)] clusters without the perturbation of other environmental effects.     

Total synthesis of 12-methoxydihydrochelerythrine and anti-tumour activity of its quaternary base: toward an efficient synthetic route for 12-alkoxybenzo[c]phenanthridine bases via naphthoquinone monooxime from 2-benzofuranyl-1-tetralone derivative

A concise total synthesis of 12-methoxydihydrochelerythrine (6), isolated from Bocconia integrifolia, is described. The synthesis features an efficient route to a 12-alkoxybenzo[c]phenanthridine skeleton via naphthoquinone monooxime 11 as a key compound. Starting from 7-methoxy-2-methylbenzo[b]furan (9), 3-aryl-1-tetralone 10 was synthesised, followed by aromatisation to 3-aryl-1-naphthol 17. After oxidative cleavage of the furan ring, basic nitrosation of naphthol 22 gave the naphthoquinone 11. The benzo[c]phenanthridine skeleton was formed by reductive cyclisation of 11. Deoxygenation of the lactam moiety in 23 afforded nor-base 32 and methylation of 32 under reductive conditions gave the target dihydro base 6 (23 steps from benzofuran 9 in 10% overall yield). The corresponding quaternary base 7 showed moderate anti-tumour activity against cancer cell lines; on NCI-H460: IC50 4.5 microM and on MDA-MB-231: IC50 1.2 microM. Introduction of a methoxy group into the 12-position of the benzo[c]phenanthridine skeleton could cause enhanced activity against MDA-MB-231 by comparison of 7 with chelerythrine (35) (IC50 5.3 microM).     

Evolution of solid phase homochirality for a proteinogenic amino acid

The inexorable evolution of solid-phase single chirality is demonstrated for the first time for a proteinogenic amino acid. Enantioenrichment is observed both under attrition-enhanced conditions and without the aid of particle grinding. Differences in the form of the conversion profiles for the process under the two sets of conditions provide suggestions concerning the mechanism of the transformation.