Cationic carbosilane dendrimers and oligonucleotide binding: an energetic affair

GENERATION 2 CATIONIC CARBOSILANE DENDRIMERS HOLD GREAT PROMISE AS INTERNALIZING AGENTS FOR GENE THERAPY AS THEY PRESENT LOW TOXICITY AND RETAIN AND INTERNALIZE GENETIC MATERIAL AS OLIGONUCLEOTIDE OR SIRNA. IN THIS WORK WE CARRIED OUT A COMPLETE IN SILICO STRUCTURAL AND ENERGETICAL CHARACTERIZATION OF THE INTERACTIONS OF A SET OF 2G CARBOSILANE DENDRIMERS, SHOWING DIFFERENT AFFINITY TOWARDS TWO SINGLE STRAND OLIGONUCLEOTIDE (ODN) SEQUENCES IN VITRO. OUR SIMULATIONS PREDICT THAT THESE FOUR DENDRIMERS AND THE RELEVANT ODN COMPLEXES ARE CHARACTERIZED BY SIMILAR SIZE AND SHAPE, AND THAT THE MOLECULE-SPECIFIC ODN BINDING ABILITY CAN BE RATIONALIZED ONLY CONSIDERING A CRITICAL MOLECULAR DESIGN PARAMETER: THE NORMALIZED EFFECTIVE BINDING ENERGY \u394GBIND,EFF/NEFF I.E., THE PERFORMANCE OF EACH ACTIVE INDIVIDUAL DENDRIMER BRANCH DIRECTLY INVOLVED IN A BINDING INTERACTIO

Emergence of highly-ordered hierarchical nanoscale aggregates on electrostatic binding of self-assembled multivalent (SAMul) cationic micelles with polyanionic heparin

We report three surfactants, with cationic N,N-di-(3-aminopropyl)-N-methylamine (DAPMA) head groups and aliphatic chains connected via an amide linkage, and investigate their ability to self-assemble and bind polyanionic heparin – a process of potential clinical importance in coagulation control. Modifying the hydrophobic chain length tunes the self-assembly event, with C16-DAPMA having the lowest critical micelle concentration and also being the optimal heparin binder. Remarkably highly structured hierarchical nanoscale aggregates are formed on binding between the spherical cationic micelles and linear polyanionic heparin. C14-DAPMA and C16-DAPMA yield organized polycrystalline assemblies as observed by transmission electron microscopy (TEM), predicted in solution by mesoscale simulations and characterized by small-angle X-ray scattering (SAXS). This confirms that the micelles remain intact during the hierarchical assembly process and become packed in a face-centered cubic manner. The nanoscale assembly formed by C16-DAPMA showed the highest degree of order. Importantly, these studies indicate the impact of hydrophobic modification on self-assembly and heparin binding, demonstrate remarkably high stability of these self-assembled micelles even when forming strong electrostatic interactions with heparin, and provide structural insights into nanoscale hierarchical electrostatic assemblies

Light driven water oxidation by a single site cobalt salophen catalyst

A salophen cobalt(II) complex enables water oxidation at neutral pH in photoactivated sacrificial cycles under visible light, thus confirming the high appeal of earth abundant single site catalysis for artificial photosynthesis

Electrostatic binding of polyanions using self-assembled multivalent (SAMul) ligand displays-structure-activity effects on DNA/heparin binding

This paper reports that modifying the ligands in self-assembled multivalent (SAMul) displays has an impact on apparent binding selectivity towards two nanoscale biological polyanions-heparin and DNA. For the nanostructures assayed here, spermidine ligands are optimal for heparin binding but spermine ligands are preferred for DNA. Probing subtle differences in such nanoscale binding interfaces is a significant challenge, and as such, several experimental binding assays-competition assays and isothermal calorimetry-are employed to confirm differences in affinity and provide thermodynamic insights. Given the dynamic nature and hierarchical binding processes involved in SAMul systems, we employed multiscale modelling to propose reasons for the origins of polyanion selectivity differences. The modelling results, when expressed in thermodynamic terms and compared with the experimental data, suggest that DNA is a shape-persistent polyanion, and selectivity originates only from ligand preferences, whereas heparin is more flexible and adaptive, and as such, actively reinforces ligand preferences. As such, this study suggests that inherent differences between polyanions may underpin subtle binding selectivity differences, and that even simple electrostatic interfaces such as these can have a degree of tunability, which has implications for biological control and regulation on the nanoscale

Measurement of CP Asymmetries and Branching Fractions in Charmless Two-Body B-Meson Decays to Pions and Kaons

We present improved measurements of CP-violation parameters in the decays $B^0 \to \pi^+ \pi^-$, $B^0 \to K^+ \pi^-$, and $B^0 \to \pi^0 \pi^0$, and of the branching fractions for $B^0 \to \pi^0 \pi^0$ and $B^0 \to K^0 \pi^0$. The results are obtained with the full data set collected at the $\Upsilon(4S)$ resonance by the BABAR experiment at the PEP-II asymmetric-energy $B$ factory at the SLAC National Accelerator Laboratory, corresponding to $467 \pm 5$ million $B\bar B$ pairs. We find the CP-violation parameter values and branching fractions $S_{\pi^+\pi^-} = -0.68 \pm 0.10 \pm 0.03, C_{\pi^+\pi^-} = -0.25 \pm 0.08 \pm 0.02, A_{K^-\pi^+} = -0.107 \pm 0.016 ^{+0.006}_{-0.004}, C_{\pi^0\pi^0} = -0.43 \pm 0.26 \pm 0.05, Br(B^0 \to \pi^0 \pi^0) = (1.83 \pm 0.21 \pm 0.13) \times 10^{-6}, Br(B^0 \to K^0 \pi^0) = (10.1 \pm 0.6 \pm 0.4) \times 10^{-6},$ where in each case, the first uncertainties are statistical and the second are systematic. We observe CP violation with a significance of 6.7 standard deviations for $B^0 \to\pi^+\pi^-$ and 6.1 standard deviations for $B^0 \to K^+ \pi^-$, including systematic uncertainties. Constraints on the Unitarity Triangle angle $\alpha$ are determined from the isospin relations among the $B \to \pi\pi$ rates and asymmetries. Considering only the solution preferred by the Standard Model, we find $\alpha$ to be in the range $[71^\circ,109^\circ]$ at the 68% confidence level.Comment: 18 pages, 11 postscript figures, submitted to Phys. Rev.

Search for lepton-number violating processes in B+ -> h- l+ l+ decays

We have searched for the lepton-number violating processes B+ -> h- l+ l+ with h- = K-/pi- and l+ = e+/mu+, using a sample of 471+/-3 million BBbar events collected with the BaBar detector at the PEP-II e+e- collider at the SLAC National Accelerator Laboratory. We find no evidence for these decays and place 90% confidence level upper limits on their branching fractions Br(B+ -> pi- e+ e+) K- e+ e+) pi- mu+ mu+) K- mu+ mu+) < 6.7 x 10^{-8}.Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D. R

Measurement of B(B-->X_s {\gamma}), the B-->X_s {\gamma} photon energy spectrum, and the direct CP asymmetry in B-->X_{s+d} {\gamma} decays

The photon spectrum in B --> X_s {\gamma} decay, where X_s is any strange hadronic state, is studied using a data sample of (382.8\pm 4.2) \times 10^6 e^+ e^- --> \Upsilon(4S) --> BBbar events collected by the BABAR experiment at the PEP-II collider. The spectrum is used to measure the branching fraction B(B --> X_s \gamma) = (3.21 \pm 0.15 \pm 0.29 \pm 0.08)\times 10^{-4} and the first, second, and third moments = 2.267 \pm 0.019 \pm 0.032 \pm 0.003 GeV,, )^2> = 0.0484 \pm 0.0053 \pm 0.0077 \pm 0.0005 GeV^2, and )^3> = -0.0048 \pm 0.0011 \pm 0.0011 \pm 0.0004 GeV^3, for the range E_\gamma > 1.8 GeV, where E_{\gamma} is the photon energy in the B-meson rest frame. Results are also presented for narrower E_{\gamma} ranges. In addition, the direct CP asymmetry A_{CP}(B --> X_{s+d} \gamma) is measured to be 0.057 \pm 0.063. The spectrum itself is also unfolded to the B-meson rest frame; that is the frame in which theoretical predictions for its shape are made.Comment: 37 pages, 19 postscript figures, submitted to Phys. Rev. D. No analysis or results have changed from previous version. Some changes to improve clarity based on interactions with Phys. Rev. D referees, including one new Figure (Fig. 13), and some minor wording/punctuation/spelling mistakes fixe

Measurement of the Time-Dependent CP Asymmetry of Partially Reconstructed B0->D*+D*- Decays

We present a new measurement of the time-dependent CP asymmetry of B0->D*+D*- decays using (471+-5) million BBbar pairs collected with the BaBar detector at the PEP-II B Factory at the SLAC National Accelerator Laboratory. Using the technique of partial reconstruction, we measure the time-dependent CP asymmetry parameters S=-0.34+-0.12+-0.05$ and C=+0.15+-0.09+-0.04. Using the value for the CP-odd fraction R_perp=0.158+-0.028+-0.006, previously measured by BaBar with fully reconstructed B0->D*+D*- events, we extract the CP-even components S+=-0.49+-0.18+-0.07+-0.04 and C+=+0.15+-0.09+-0.04. In each case, the first uncertainty is statistical and the second is systematic; the third uncertainty on S+ is the contribution from the uncertainty on R_perp. The measured value of the CP-even component S+ is consistent with the value of sin(2Beta) measured in b->(ccbar)s transitions, and with the Standard Model expectation of small penguin contributions.Comment: 17 pages, 7 figures, submitted to Physical Review

Measurement of Branching Fractions and Rate Asymmetries in the Rare Decays B -> K(*) l+ l-

In a sample of 471 million BB events collected with the BABAR detector at the PEP-II e+e- collider we study the rare decays B -> K(*) l+ l-, where l+ l- is either e+e- or mu+mu-. We report results on partial branching fractions and isospin asymmetries in seven bins of di-lepton mass-squared. We further present CP and lepton-flavor asymmetries for di-lepton masses below and above the J/psi resonance. We find no evidence for CP or lepton-flavor violation. The partial branching fractions and isospin asymmetries are consistent with the Standard Model predictions and with results from other experiments.Comment: 16 pages, 14 figures, accepted by Phys. Rev.

Precise Measurement of the e+ e- --> pi+ pi- (gamma) Cross Section with the Initial-State Radiation Method at BABAR

A precise measurement of the cross section of the process $e^+e^-\to\pi^+\pi^-(\gamma)$ from threshold to an energy of 3GeV is obtained with the initial-state radiation (ISR) method using 232fb$^{-1}$ of data collected with the BaBar detector at $e^+e^-$ center-of-mass energies near 10.6GeV. The ISR luminosity is determined from a study of the leptonic process $e^+e^-\to\mu^+\mu^-(\gamma)\gamma_{\rm ISR}$, which is found to agree with the next-to-leading-order QED prediction to within 1.1%. The cross section for the process $e^+e^-\to\pi^+\pi^-(\gamma)$ is obtained with a systematic uncertainty of 0.5% in the dominant $\rho$ resonance region. The leading-order hadronic contribution to the muon magnetic anomaly calculated using the measured $\pi\pi$ cross section from threshold to 1.8GeV is $(514.1 \pm 2.2({\rm stat}) \pm 3.1({\rm syst}))\times 10^{-10}$.Comment: 58 pages, 56 figures, to be submitted to Phys. Rev.