Heterocyclic diamidine interactions at AT base pairs in the DNA minor groove: effects of heterocycle differences, DNA AT sequence and length

Given the increasing significance of diamidines as DNA-targeted therapeutics and biotechnology reagents, it is important to establish the variations in thermodynamic quantities that characterize the interactions of closely related compounds to different sequence AT binding sites. In this study, an array of methods including biosensor-surface plasmon resonance (SPR), isothermal titration microcalorimetry (ITC), circular dichroism (CD), thermal melting (Tm) and molecular modeling have been used to characterize the binding of dicationic diamidines related to DB75 (amidine-phenyl-furan-phenyl-amidine) with alternating and nonalternating AT sequences. Conversion of the central furan of DB75 to other similar groups, such as thiophene or selenophene, can yield compounds with increased affinity and sequence binding selectivity for the minor groove. Calorimetric measurements revealed that the thermodynamic parameters (Delta G, Delta H, Delta S) that drive diamidine binding to alternating and nonalternating oligomers can be quite different and depend on both DNA sequence and length. Small changes in a compound can have major effects on DNA interactions. By choosing an appropriate central group it is possible to "tune" the shape of the molecule to match DNA for enhanced affinity and sequence recognition.     

Computable error bounds for pointwise derivatives of a Neumann problem

In this paper we discuss the recovery of derivatives and thecomputation of rigorous and useful upper bounds for the pointwiseerror in the recovered derivatives, for finite element approximationsof the Laplace equation with Neumann boundary conditions, especiallyat points close to or on a smooth, curved boundary. We analyzethe dipole image technique for the case of curved boundaries,and show how to compute reliable recovered derivatives and errorbounds even in the limiting case of points lying on the curvedboundary. Numerical experiments show reasonably tight errorbounds for points both close to and away from a curved boundary.     

17O NMR spectroscopy: unusual substituent effects in para-substituted benzyl alcohols and acetates

The ¹⁷O chemical shifts for $\text{para}$-substituted benzyl alcohols and acetates were measured: electron donating substituents resulted in deshielding and electron withdrawing groups resulted in shielding of the chemical shift; the data are correlated by DSP treatment.     

Natural abundance 17O NMR spectroscopy of heterocyclic N-oxides and Di N-oxides. Structural effects

The ¹⁷O chemical shift data for a series of azine N-oxides, diazine N-oxides and di-N-oxides at natural abundance are reported. Isomeric methyl substituted quinoline N-oxides exhibited chemical shifts which are interpreted in terms of electronic and compressional effects. The ¹⁷O chemical shift for 8-methylquinoline N-oxide (370 ppm) is deshielded by 25 ppm more than predicted, based upon electronic considerations. The ¹⁷O chemical shift for the N-oxide of 8-hydroxyquinoline (289 ppm) is substantially shielded as a result of intramolecular hydrogen bonding. The relative ¹⁷O chemical shifts for diazine N-oxides of pyrazine, pyridazine and pyrimidine follow predictions based on back donation considerations. Because of solubility limitations, spectra of only two N,N′-dioxides were obtained. The chemical shift of benzopyrazine di N-oxide in acetonitrile was shielded by 18 ppm compared to that of its mono N-oxide.     

Analytic determination of an optimal human motion

A three-rigid-links model is constructed for a gymnast performing a kip-up maneuver on a horizontal bar. Equations of motion with constrained, voluntary torques at hip and shoulder joints give a well-posed optimal control problem when boundary conditions and a performance criterion for the maneuver are specified. An approximate numerical solution for the minimum-time performance of this nonlinear process is obtained by the method of steepest descent. Results of the computations are compared with experimental results. Difficulties of solving human motion problems by existing numerical methods are pointed out.Notation element 1 arm system - element 2 head-neck-torso system - element 3 leg system - angle between element 1 and vertical - angle between elements 1 and 2 - angle between elements 2 and 3 - O ₁ hinge axis between elements 1 and 2 - O ₂ hinge axis between elements 2 and 3 - O ₃ hinge axis representing fist-horizontal-bar system - T ₁ torque between elements 1 and 2 - T ₂ torque between elements 2 and 3 - l ₁ distance betweenO ₃ andO ₁ - l ₂ distance betweenO ₁ andO ₂ - I _i moment of inertia of elementi about its CG about an axis perpendicular to the plane of motion,i = 1,2,3 - I _r moment of inertia of the horizontal bar about its longitudinal axis - m _i mass of elementi, i=1,2,3 - r ₁ distance between O₃ and CG of element 1 - r ₂ distance between O₁ and CG of element 2 - r ₃ distance between O₁ and CG of element 3 - g acceleration due to gravity This research was partially supported by the National Science Foundation through Grants Nos. GK-4944 and GK-37024x.Appreciation of Dr. Tom Bullock for discussion on numerical optimization techniques and Mr. Tom Boone for his services as an experimental test subject is gratefully acknowledged.     

Simple amine/Pd(OAc)(2)-catalyzed suzuki coupling reactions of aryl bromides under mild aerobic conditions

A new palladium catalyst (DAPCy) made from Pd(OAc)(2) and commercially available, inexpensive dicyclohexylamine has been developed for the Suzuki coupling reaction of aryl bromides with boronic acids to give the coupling products in good to high yields. The air-stable catalyst was characterized and well-defined by X-ray crystallography. A catalytic system involving DAPCy in dioxane demonstrates a temperature-dependent reactivity toward aryl bromides with different electronic substituents, and selectively couples electron-deficient aryl bromides with boronic acids over electron-rich ones at room temperature. Another catalytic system employing DAPCy in EtOH provides a general and convenient method to prepare biaryls from aryl bromides and boronic acids with a broad range of functional groups at room temperature and under aerobic conditions.     

trans-Pd(OAc)2(Cy2NH)2 catalyzed Suzuki coupling reactions and its temperature-dependent activities toward aryl bromides

A new catalytic system based on Pd-simple amines for Suzuki coupling reactions of aryl bromides is described. A well-defined air-stable complex, trans-Pd(OAc)₂(Cy₂NH)₂ effectively promotes Suzuki couplings of aryl bromides with a range of aryl boronic acids to give diaryl products in high yields. It also exhibits temperature-dependent activity toward aryl bromides bearing different electronic substituents under reaction conditions.     

Effective interactions and block diagonalization in quantum-mechanical problems

Many models of condensed-matter systems have interactions with unexpected features: for example, exclusively distant-neighbor spin–orbit interactions. On first inspection these interactions seem physically questionable in view of the basis states used. However, such interactions can be physically reasonable if the model is an effective one, in which the basis states are not exactly as described, but instead include components of states removed from the problem. Mathematically, an effective model results from partitioning the Hamiltonian matrix, which can be accomplished by energy-dependent or energy-independent methods. We examine effective models of both types, with a special emphasis on energy-independent approaches. We show that an appropriate choice of basis makes the partitioning simpler and more accurate. We illustrate the method by calculating the spin–orbit splitting in graphene.