Stabilization and structure of telomeric and c-myc region intramolecular G-quadruplexes: the role of central cations and small planar ligands

A promising approach for anticancer strategies is the stabilization of telomeric DNA into a G-quadruplex structure. To explore the intrinsic stabilization of folded G-quadruplexes, we combined electrospray ionization mass spectrometry, ion mobility spectrometry, and molecular modeling studies to study different DNA sequences known to form quadruplexes. Two telomeric DNA sequences of different lengths and two DNA sequences derived from the NHE III1 region of the c-myc oncogene (Pu22 and Pu27) were studied. NH4+ and the ligands PIPER, TMPyP4, and the three quinacridines MMQ1, MMQ3, and BOQ1 were complexed with the DNA sequences to determine their effect on the stability of the G-quadruplexes. Our results demonstrate that G-quadruplex intramolecular folds are stabilized by NH4+ cations and the ligands listed. Furthermore, the ligands can be classified according to their ability to stabilize the quadruplexes and end stacking is shown to be the dominant mode for ligand attachment. In all cases our solvent-free experimental observations and theoretical modeling reveal structures that are highly relevant to the solution-phase structures.     

Optimization of algorithms for ion mobility calculations

Ion mobility spectrometry (IMS) is increasingly employed to probe the structures of gas-phase ions, particularly those of proteins and other biological macromolecules. This process involves comparing measured mobilities to those computed for potential geometries, which requires evaluation of orientationally averaged cross sections using some approximate treatment of ion-buffer gas collisions. Two common models are the projection approximation (PA) and exact hard-spheres scattering (EHSS) that represent ions as collections of hard spheres. Though calculations for large ions and/or conformer ensembles take significant time, no algorithmic optimization had been explored. Previous EHSS programs were dominated by ion rotation operations that allow orientational averaging. We have developed two new algorithms for PA and EHSS calculations: one simplifies those operations and greatly reduces their number, and the other disposes of them altogether by propagating trajectories from a random origin. The new algorithms were tested for a representative set of seven ion geometries including diverse sizes and shapes. While the best choice depends on the geometry in a nonobvious way, the difference between the two codes is generally modest. Both are much more efficient than the existing software, for example faster than the widely used Mobcal (implementing EHSS) approximately 10-30-fold.     

A two transition state model for radical-molecule reactions: applications to isomeric branching in the OH-isoprene reaction

A two transition state model is applied to the prediction of the isomeric branching in the addition of hydroxyl radical to isoprene. The outer transition state is treated with phase space theory fitted to long-range transition state theory calculations on an electrostatic potential energy surface. High-level quantum chemical estimates are applied to the treatment of the inner transition state. A one-dimensional master equation based on an analytic reduction from two-dimensions for a particular statistical assumption about the rotational part of the energy transfer kernel is employed in the calculation of the pressure dependence of the addition process. We find that an accurate treatment of the two separate transition state regions, at the energy and angular momentum resolved level, is essential to the prediction of the temperature dependence of the addition rate. The transition from a dominant outer transition state to a dominant inner transition state is shown to occur at about 275 K, with significant effects from both transition states over the 30-500 K temperature range. Modest adjustments in the ab initio predicted inner saddle point energies yield predictions that are in quantitative agreement with the available high-pressure limit experimental observations and qualitative agreement with those in the falloff regime. The theoretically predicted capture rate is reproduced to within 10% by the expression [1.71 x 10(-10)(T/298)(-2.58) exp(-608.6/RT) + 5.47 x 10(-11)(T/298)-1.78 exp(-97.3/RT); with R = 1.987 and T in K] cm3 molecule(-1) s(-1) over the 30-500 K range. A 300 K branching ratio of 0.67:0.02:0.02:0.29 was determined for formation of the four possible OH-isoprene adduct isomers 1, 2, 3, and 4, respectively, and was found to be relatively insensitive to temperature. An Arrhenius activation energy of -0.77 kcal/mol was determined for the high-pressure addition rate constants around 300 K.     

Multiple additions of phenylgermanium ligands to tetraruthenium and tetraosmium carbonyl cluster complexes

Three new compounds, Ru4(mu4-GePh)2(mu-GePh2)2(mu-CO)2(CO)8 (11), Ru4(mu4-GePh)2(mu-GePh2)3(mu-CO)(CO)8 (12), and Ru4(mu4-GePh)2(mu-GePh2)4(CO)8 (13), were obtained from the reaction of H(4)Ru(4)(CO)12 with excess Ph(3)GeH in octane (11 and 12) or decane (13) reflux. Compound 11 was converted to compound 13 by reaction with Ph(3)GeH by heating solutions in nonane solvent to reflux. Compounds 11-13 each contain a square-type arrangement of four Ru atoms capped on each side by a quadruply bridging GePh ligand to form an octahedral geometry for the Ru(4)Ge(2) group. Compound 11 also contains two edge-bridging GePh(2) groups on opposite sides of the cluster and two bridging carbonyl ligands. Compound 12 contains three edge-bridging GePh(2) groups and one bridging carbonyl ligand. Compound 13 contains four bridging GePh(2) groups, one on each edge of the Ru4 square. The reaction of H(4)Os(4)(CO)12 with excess Ph(3)GeH in decane at reflux yielded two new tetraosmium cluster complexes, Os4(mu4-GePh)2(mu-GePh2)3(mu-CO)(CO)8 (14) and Os4(mu4-GePh)2(mu-GePh(2))4(CO)8 (15). These compounds are structurally similar to compounds 12 and 13, respectively.     

Rapid synthesis of 3-amino-imidazopyridines by a microwave-assisted four-component coupling in one pot

The rapid and efficient synthesis of various 2,6-disubstituted-3-amino-imidazopyridines using a microwave-assisted one-pot cyclization/Suzuki coupling approach is described. The utility of a 2-aminopyridine-5-boronic acid pinacol ester as a robust and versatile building block for the synthesis of diverse compound libraries is emphasized. The boronate functional group is remarkably tolerant to the Lewis acid catalyzed cyclizations, and the subsequent Pd(0)-catalyzed Suzuki coupling reactions proceed cleanly in the presence of magnesium salts. This work highlights the vast potential of microwave-assisted, metal-catalyzed, multicomponent reactions.     

Directed electrodeposition of polymer films using spatially controllable electric field gradients

We report a method for the directed electrodeposition of polymer films in various patterns using spatially controllable electric field gradients. One- and two- dimensional surface electric field gradients were produced by applying different potential values at spatially distinct locations on an electrode surface. Variations in the resulting local electrochemical potentials were used to spatially manipulate the rate of electrodeposition of several polymers. By controlling the electric field gradient in the presence of sequentially varying deposition solutions, complex polymer patterns could be produced. One-dimensional structures consisting of alternating bands of polyaniline and either poly(phenylene) oxide or poly(aminophenylene) oxide were produced, as well as more complex two-dimensional structures. Film characterization was achieved through optical imaging, UV-vis spectroscopy, and ellipsometry. Results indicate that this directed deposition technique is a simple strategy to create complex, millimeter-sized surface patterns of electrodeposited materials.     

Nanotribology of octadecyltrichlorosilane monolayers and silicon: self-mated versus unmated interfaces and local packing density effects

We use atomic force microscopy (AFM) to determine the frictional properties of nanoscale single-asperity contacts involving octadecyltrichlorosilane (OTS) monolayers and silicon. Quantitative AFM measurements in the wearless regime are performed using both uncoated and OTS-coated silicon AFM tips in contact with both uncoated and OTS-coated silicon surfaces, providing four pairs of either self-mated or unmated interfaces. Striking differences in the frictional responses of the four pairs of interfaces are found. First, lower friction occurs with OTS present on either the tip or substrate, and friction is yet lower when OTS is present on both. Second, the shape of the friction versus load plot strongly depends on whether the substrate is coated with OTS, regardless of whether the tip is coated. Uncoated substrates exhibit the common sublinear dependence, consistent with friction being directly proportional to the area of contact. However, coated substrates exhibit an unusual superlinear dependence. These results can be explained qualitatively by invoking molecular plowing as a significant contribution to the frictional behavior of OTS. Direct in situ comparison of two intrinsic OTS structural phases on the substrate is also performed. We observe frictional contrast for different local molecular packing densities of the otherwise identical molecules. The phase with lower packing density exhibits higher friction, in agreement with related previous work, but decisively observed here in single, continuous images involving the same molecules. Lateral stiffness measurements show no distinction between the two OTS structural phases, demonstrating that the difference in friction is not due to divergent stiffnesses of the two phases. Therefore, the packing density directly affects the interface's intrinsic resistance to friction, that is, the interfacial shear strength.     

Effects of catalyst introduction methods using PAMAM dendrimers on selective electroless nickel deposition on polyelectrolyte multilayers

We studied the effects of catalyst introduction methods using poly(amidoamine) (PAMAM) dendrimers on the nickel patterning of polyelectrolyte multilayer (PEM)-coated substrates. Three different approaches to palladium catalyst introduction using microcontact printing as the patterning technique were utilized and compared. The catalyst introduction methods are (1) direct catalyst stamping, (2) directed assembly using PAMAM dendrimer stamping, and (3) catalyst encapsulation and reduction to nanoparticles within PAMAM dendrimers before stamping. After patterning, the sample surfaces were placed in an electroless bath where nickel was selectively plated onto the patterns. The patterned surfaces were characterized using optical microscopy, atomic force microscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The metal plating rates on different homogeneous surfaces that simulate the patterned surfaces were measured using a quartz crystal microbalance. In addition, the effect of PEM film thickness (i.e., number of bilayers) on the selectivity of nickel patterning was investigated.     

Controlling electron transfer dynamics in donor-bridge-acceptor molecules by increasing unpaired spin density on the bridge

A t-butylphenylnitroxide (BPNO*) stable radical is attached to an electron donor-bridge-acceptor (D-B-A) system having well-defined distances between the components: MeOAn-6ANI-Ph(BPNO*)-NI, where MeOAn=p-methoxyaniline, 6ANI=4-(N-piperidinyl)naphthalene-1,8-dicarboximide, Ph=phenyl, and NI=naphthalene-1,8:4,5-bis(dicarboximide). MeOAn-6ANI, BPNO*, and NI are attached to the 1, 3, and 5 positions of the Ph bridge, respectively. Time-resolved optical and EPR spectroscopy show that BPNO* influences the spin dynamics of the photogenerated triradical states 2,4(MeOAn+*-6ANI-Ph(BPNO*)-NI-*), resulting in slower charge recombination within the triradical, as compared to the corresponding biradical lacking BPNO*. The observed spin-spin exchange interaction between the photogenerated radicals MeOAn+* and NI-* is not altered by the presence of BPNO*. However, the increased spin density on the bridge greatly increases radical pair (RP) intersystem crossing from the photogenerated singlet RP to the triplet RP. Rapid formation of the triplet RP makes it possible to observe a biexponential decay of the total RP population with components of tau=740 ps (0.75) and 104 ns (0.25). Kinetic modeling shows that the faster decay rate is due to rapid establishment of an equilibrium between the triplet RP and the neutral triplet state resulting from charge recombination, whereas the slower rate monitors recombination of the singlet RP to ground state.     

Star‐Shaped Polyaromatic Ethers Coordinated to Redox‐Active Cyclopentadienyliron Moieties

This communication is focused on the controlled design of star‐shaped aromatic ethers with pendent cyclopentadienyliron moieties. A trimetallic core was prepared, which was then reacted with a number of oligomeric ether complexes to give star‐shaped polymers with six, nine, twelve and fifteen pendent cationic cyclopentadienyliron moieties. Cyclic voltammetric studies showed reduction of the iron centers between –0.99 and –1.41 V. Thermogravimetric analysis showed that loss of the metallic moieties occurred between 225 and 284°C.