Oligo(p-phenylenevinylene)-peptide conjugates: synthesis and self-assembly in solution and at the solid-liquid interface

Two oligo(p-phenylenevinylene)-peptide hybrid amphiphiles have been synthesized using solid- and liquid-phase strategies. The amphiliphiles are composed of a pi-conjugated oligo(p-phenylenevinylene) trimer (OPV) which is coupled at either a glycinyl-alanyl-glycinyl-alanyl-glycine (GAGAG) silk-inspired beta-sheet or a glycinyl-alanyl-asparagyl-prolyl-asparagy-alanyl-alanyl-glycine (GANPNAAG) beta-turn forming oligopeptide sequence. The solid-phase strategy enables one to use longer peptides if strong acidic conditions are avoided, whereas the solution-phase coupling gives better yields. The study of the two-dimensional (2D) self-assembly of OPV-GAGAG by scanning tunneling microscopy (STM) at the submolecular level demonstrated the formation of bilayers in which the molecules are lying antiparallel in a beta-sheet conformation. In the case of OPV-GANPNAAG self-assembled monolayers could not be observed. Absorption, fluorescence, and circular dichroism studies showed that OPV-GAGAG and OPV-GANPNAAG are aggregated in a variety of organic solvents. In water cryogenic temperature transmission electron microscopy (cryo-TEM), atomic force microscopy (AFM), light scattering, and optical studies reveal that self-assembled nanofibers are formed in which the helical organization of the OPV segments is dictated by the peptide sequence.     

On the convergence of Z-averaged perturbation theory

Very high order open-shell Z-averaged perturbation theory (ZAPT) energies, equilibrium bond lengths, and harmonic vibrational frequencies have been computed for a suite of small molecules using a determinantal algorithm. The convergence of ZAPTn energies is compared to alternative Moller-Plesset (MP) perturbation theories built on restricted open-shell Hartree-Fock (ROMP, RMP, OPT1, and OPT2) and unrestricted Hartree-Fock (UMP) reference wave functions for NH(2) at three N-H bond lengths and for CN. The ZAPTn energy series closely parallel those of RMPn and ROMPn theories for these systems. Further, we examine the convergence of ZAPTn energies, equilibrium bond lengths (r(e)), and harmonic vibrational frequencies (omega(e)) for X (2)Sigma(g)(+) CN, X (4)Sigma(g) (-) C(2)(+), and b (2)Delta(g) C(2)(+), tracking oscillations in the energy series for the challenging latter system to order 1000. Finally, we obtain r(e) and omega(e) values from explicit ZAPT2 and ZAPT4 computations with a triple-zeta plus double polarization basis set. The ensuing results are very close to those from second- and fourth-order RMP and ROMP for the NO and CN molecules but are significantly closer to experiment in the case of (3)Sigma(g)(-) O(2). The ZAPTn series exhibit all the fascinating diversity of behavior previously observed for closed-shell MPn theory. Particularly encouraging is the ability of Feenberg transformations to remove erratic, strongly oscillatory, and divergent behavior that may occur in ZAPTn series and provide systematic improvements toward the full configuration interaction limit. In light of the appealing mathematical properties of ZAPT and similarity of results to those from the oft-applied RMP theory, coupled with the reductions in computational cost inherent in the ZAPT method relative to theories requiring different orbitals for different spins, we recommend low-order ZAPT for general applications to open-shell systems, particularly in cases where spin contamination is of concern.     

Self-assembly of a cyclic metalladecapyridine from the reaction of 2,6-bis(bis(2-pyridyl)methoxymethane)pyridine with silver(I)

Reaction of Ag( p-MeC 6H 4SO 3) with 2,6-bis(bis(2-pyridyl)methoxymethane)pyridine (PY5) in CH 2Cl 2 gave [Ag (I) 2(PY5) 2](p-MeC 6H 4SO 3) 2 (1). Treatment of 2,6-bis(bis(2-pyridyl)hydroxymethane)pyridine (PY5-OH) with AgNO 3 in MeOH gave [Ag (I) 2(PY5-OH) 2](NO3) 2 (2); in the presence of PPh 3, this reaction afforded [Ag (I)(PY5-OH)(PPh 3)]NO 3 (3). The structures of 1- 3 have been determined by X-ray crystal analysis, revealing four-coordinate Ag (I) ions in these complexes. Both 1 and 2 feature a quadruply branched 28-membered C 16N 10M 2 metallamacrocycle fused to 10 pyridyl groups. On the basis of (1)H NMR measurements, the dinuclear 1 and 2 dissociate into a mononuclear complex upon dissolving in MeCN but in MeOH an equilibrium between the mono- and dinuclear species can be detected.     

Application of mean-field and surface-hopping approaches for interrogation of the Xe3+ molecular ion photoexcitation dynamics

The dissociation dynamics of the excited Xe(3) (+) molecular ion through the Pi(12)(u) and Pi(12)(g) conical intersection was interrogated by computational simulation in which no adjustable parameters were used. The electronic ground and excited state potential energy surfaces were generated by the diatomics-in-molecules method, and the Ehrenfest mean-field and Tully surface-hopping approaches treated the nonadiabatic interactions. Reproduction of the experimental spectrum of the symmetric photofragmentation as a function of excitation energy was obtained within the region of interest (2.5-3.75 eV), with the exception of a 0.25 eV width on the red side of the spectral apex. Good agreement was obtained with the experimental dissociated photofragment kinetic energy spectra. It was determined that the greatest contribution to the nonadiabatic coupling between the two states originated from the bending vibrational mode of the molecule in the Sigma(12)(u), ground electronic state before excitation.     

The Strongest Acid: Protonation of Carbon Dioxide

The strongest carborane acid, H(CHB₁₁F₁₁), protonates CO₂ while traditional mixed Lewis/Brønsted superacids do not. The product is deduced from IR spectroscopy and calculation to be the proton disolvate, H(CO₂)₂⁺. The carborane acid H(CHB₁₁F₁₁) is therefore the strongest known acid. The failure of traditional mixed superacids to protonate weak bases such as CO₂ can be traced to a competition between the proton and the Lewis acid for the added base. The high protic acidity promised by large absolute values of the Hammett acidity function (H₀) is not realized in practice because the basicity of an added base is suppressed by Lewis acid/base adduct formation.     

Combining Biomimetic Block Copolymer Worms with an Ice‐Inhibiting Polymer for the Solvent‐Free Cryopreservation of Red Blood Cells

The first fully synthetic polymer‐based approach for red‐blood‐cell cryopreservation without the need for any (toxic) organic solvents is reported. Highly hydroxylated block copolymer worms are shown to be a suitable replacement for hydroxyethyl starch as a extracellular matrix for red blood cells. When used alone, the worms are not a particularly effective preservative. However, when combined with poly(vinyl alcohol), a known ice‐recrystallization inhibitor, a remarkable additive cryopreservative effect is observed that matches the performance of hydroxyethyl starch. Moreover, these block copolymer worms enable post‐thaw gelation by simply warming to 20 °C. This approach offers a new solution for both the storage and transport of red blood cells and also a convenient matrix for subsequent 3D cell cultures.     

Discovery of a Highly Selective Glycogen Synthase Kinase‐3 Inhibitor (PF‐04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging

Glycogen synthase kinase‐3 (GSK‐3) regulates multiple cellular processes in diabetes, oncology, and neurology. N‐(3‐(1H‐1,2,4‐triazol‐1‐yl)propyl)‐5‐(3‐chloro‐4‐methoxyphenyl)oxazole‐4‐carboxamide (PF‐04802367 or PF‐367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK‐3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF‐367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF‐367 is ideal for discovery of radiopharmaceuticals for GSK‐3 in the central nervous system. A ¹¹C‐isotopologue of PF‐367 was synthesized and preliminary PET imaging studies in non‐human primates confirmed that we have overcome the two major obstacles for imaging GSK‐3, namely, reasonable brain permeability and displaceable binding.     

Stacking and Electrostatic Interactions Drive the Stereoselectivity of Silylium‐Ion Asymmetric Counteranion‐Directed Catalysis

Computational analysis shows that the enantioselectivity of asymmetric Lewis‐acid organocatalysis of the Diels–Alder cycloaddition of cyclopentadiene to cinnamates arises from stacking interactions that favor the addition of the diene to the more hindered face of the dienophile, while electrostatic interactions control the diastereoselectivity by selectively stabilizing the endo transition state. These results not only explain the stereoselectivity of these silylium‐ion‐ACDC reactions but should also guide the development of more effective ion‐pairing asymmetric organocatalysts.     

Self‐Assembly of the Cyclic Lipopeptide Daptomycin: Spherical Micelle Formation Does Not Depend on the Presence of Calcium Chloride

The cyclic lipopeptide Daptomycin, used as a treatment for infections where antimicrobial resistance is observed, is shown to self‐assemble into spherical micelles above a critical aggregation concentration. Micelles are observed either in the absence or presence of CaCl₂, in contrast to claims in the literature that CaCl₂ is required for micellization.     

An agent-based model of organizational ambidexterity decisions and strategies in new product development

Organizational ambidexterity, defined as the pursuit of both exploitation and exploration, has become an important topic in the study of organizations, especially in innovation management theory. Previous literature has not focused on the strategic (game-theoretic) aspects of organizational ambidexterity or on its decision-making aspects. Little is known about how or even whether the decision to adopt ambidexterity is competitively advantageous in the presence of diverse strategies that competitors may adopt. This facet of the subject is inherently game-theoretic; the value of a decision by one firm depends in part on decisions made by other firms. This paper initiates systematic investigation of these strategic aspects, including the overall performance of available strategies. Specifically, this study examines questions of ambidexterity-related strategy performance in the context of new product development. The main contributions are (1) to introduce and make available to the research community an agent-based model and decision support system that captures many of the key aspects and tradeoffs, which have been identified in the literature, of the exploration–exploitation dilemma faced by firms in the new product development process, with a focus on organizations’ product investment decisions and (2) to report on results obtained from the model, calibrated with available data from the literature, augmented by new data collected from interviews with practitioners.