Acevedochristensen4237

The inherent conformational preferences of the neutral β-peptide foldamer series, Ac-(ACHC)n-NHBn, n = 2-4, are studied in the gas phase using conformation-specific IR-UV double resonance methods. The cyclically constrained chiral β-amino acid cis-2-aminocyclohexane carboxylic acid (ACHC) is designed to bring both right- and left-handed helices into close energetic proximity. Comparison of the infrared spectra in the NH stretch and amide I/II regions with the predictions of DFT calculations lead to the unambiguous assignment of four out of the six observed conformations of the molecules in this series, while corroborating computational and spectral evidence, affords tentative assignments of the remaining two conformers for which IR data were not recorded. NU7026 The observed structures fall into one of two conformational families a right-handed 12/10-mixed helix or its "cap-disrupted" left-handed helical analogue, which coexist with significant populations. Site-specific and stereospecific methylation on the cyclohexane backbone at the dipeptide (n = 2) level is also tested as a means to sterically lock in a predetermined cyclohexane chair conformation. These substitutions are proven to be a means of selectively driving formation of one helical screw sense or the other. Calculated relative energies and free energies of all possible structures for the molecules provide strong supporting evidence that the rigid nature of the ACHC residue confers unusual stability to the 12/10-mixed helix conformation, regardless of local environment, temperature, or C-terminal capping unit. The simultaneous presence of both handed helices offers unique opportunities for future studies of their interconversion.Enhanced sampling techniques are a promising approach to obtain reliable binding free-energy profiles for flexible protein-ligand complexes from molecular dynamics (MD) simulations. To put four popular enhanced sampling techniques to a biologically relevant and challenging test, we studied the partial dissociation of an antigenic peptide from the Major Histocompatibility Complex I (MHC I) HLA-B*3501 to systematically investigate the performance of umbrella sampling (US), replica exchange with solute tempering 2 (REST2), bias exchange umbrella sampling (BEUS, or replica-exchange umbrella sampling), and well-tempered metadynamics (MTD). With regard to the speed of sampling and convergence, the peptide-MHC I complex (pMHC I) under study showcases intrinsic strengths and weaknesses of the four enhanced sampling techniques used. We found that BEUS can best handle the sampling challenges that arise from the coexistence of an enthalpically and an entropically stabilized free-energy minimum in the pMHC I under study. These findings might also be relevant for other flexible biomolecular systems with competing enthalpically and entropically stabilized minima.We report a novel reductive interrupted Fischer indolization process for the concise assembly of the 20-oxoaspidospermidine framework. This rapid complexity generating route paves the way toward various dihydroindole Aspidosperma alkaloids with different C-5 side chain redox patterns. The end-game redox modulations were accomplished by modified Wolff-Kishner reaction and photo-Wolff rearrangement, enabling the total synthesis of (-)-aspidospermidine, (-)-limaspermidine, and (+)-17-demethoxy-N-acetylcylindrocarine and the formal total synthesis of (-)-1-acetylaspidoalbidine.We report on the effect of the substrate on electrochemical deposition of Cu from deep eutectic solvent ethaline. We investigated the polarization behavior during electrodeposition of Cu on Pt and glassy carbon (GC) from both Cu2+ and Cu+ containing ethaline using cyclic voltammetry (CV). Formation of bulk Cu deposits on both substrates underwent nucleation and growth processes; however, the nucleation was considerably sluggish on GC compared to Pt. While experiments in Cu+ solutions indicated that coalescence of Cu islands on Pt is a slow process and that its surface may not be fully covered by Cu, such determination of Cu coverage could not be made on GC. Cu dissolution is also slower from GC than from Pt. It was observed that CV of Cu deposition on GC is influenced by the surface preparation method. Since ethaline has high chloride concentration, a parallel study in aqueous 3 M NaCl solution was conducted in order to examine the influence of the chloride medium on the electrodeposition process. This revealed that electrodeposition in both media occurred in the same manner but with different charge and mass transfer rates caused by the differences in viscosity and chloride concentrations of the two solutions.Extending the bandwidth of triplet excited-state absorption in transition-metal complexes is appealing for developing broadband reverse saturable absorbers. Targeting this goal, five bis-terdentate iridium(III) complexes (Ir1-Ir5) bearing trans-bis-cyclometalating (C^N^C) and 4'-R-2,2'6',2″-terpyridine (4'-R-tpy) ligands were synthesized. The effects of the structural variation in cyclometalating ligands and substituents at the tpy ligand on the photophysics of these complexes have been systematically explored using spectroscopic methods (i.e., UV-vis absorption, emission, and transient absorption spectroscopy) and time-dependent density functional theory (TDDFT) calculations. All complexes exhibited intensely structured 1π,π* absorption bands at Ir3. The RSA trend corresponded well with the strength of the excited-state and ground-state absorption differences (ΔOD) at 532 nm for these complexes.Thermally activated photophysical processes are ubiquitous in numerous organic and metal-organic molecules, leading to chromophores with excited-state properties that can be considered an equilibrium mixture of the available low-lying states. Relative populations of the equilibrated states are governed by temperature. Such molecules have been devised as high quantum yield emitters in modern organic light-emitting diode technology and for deterministic excited-state lifetime control to enhance chemical reactivity in solar energy conversion and photocatalytic schemes. The recent discovery of thermally activated photophysics at CdSe nanocrystal-molecule interfaces enables a new paradigm wherein molecule-quantum dot constructs are used to systematically generate material with predetermined photophysical response and excited-state properties. Semiconductor nanomaterials feature size-tunable energy level engineering, which considerably expands the purview of thermally activated photophysics beyond what is possible using only molecules. This Perspective is intended to provide a nonexhaustive overview of the advances that led to the integration of semiconductor quantum dots in thermally activated delayed photoluminescence (TADPL) schemes and to identify important challenges moving into the future. The initial establishment of excited-state lifetime extension utilizing triplet-triplet excited-state equilibria is detailed. Next, advances involving the rational design of molecules composed of both metal-containing and organic-based chromophores that produce the desired TADPL are described. Finally, the recent introduction of semiconductor nanomaterials into hybrid TADPL constructs is discussed, paving the way toward the realization of fine-tuned deterministic control of excited-state decay. It is envisioned that libraries of synthetically facile composites will be broadly deployed as photosensitizers and light emitters for numerous synthetic and optoelectronic applications in the near future.In this Review, we highlight well-described and emerging polyanions, and the way these molecules can be targeted in the design of potential therapeutics (synthetic and biologics) with applications in thrombosis and hemostasis. It is important to strike a balance between bleeding and clotting. In thrombosis, unwanted blood clots are formed in the lumen of a blood vessel, obstructing the flow of blood through the circulatory system. Over many years of research, several polyanionic biopolymers that can either impede (anticoagulant) or promote (procoagulant) blood clotting have been identified. Mediators impeding blood clotting, including polyanionic polysaccharides such as heparins and heparin mimics, are widely used as antithrombotics, although they impart adverse complications such as bleeding. Emerging synthetic polycations and well-described cationic proteins that are specifically designed to neutralize the biological activity of heparins to prevent bleeding complications are discussed. On the other hand, there is growing evidence that several polyanions bear a procoagulant nature in blood; polyphosphate (polyP), neutrophil extracellular traps (NETs), extracellular RNA, and cell-free DNA are shown to promote blood clotting. Recent research highlights the use of polycations and enzymes that either inhibit or cleave these procoagulant polyanions and demonstrates the proof-of-concept design of new antithrombotics without bleeding side effects. Additional studies have shown that some of these procoagulant polyanions can be used as a hemostat to prevent bleeding in an emergency. There are significant opportunities for chemists in the design of new inhibitors and agents with improved selectivity toward these biological polyanions, furthering the development of novel therapeutics.Liquid fouling can reduce the functionality of critical engineering surfaces. Recent studies have shown that minimizing contact angle hysteresis is a promising strategy for achieving omniphobic (all-liquid repellent) properties, thereby inhibiting fouling. Prior omniphobic films can repel a broad range of liquids, but the applicability of these coatings has always been limited to silicon wafers or smooth glass. Here we develop a facile procedure to generate an omniphobic coating on any surface, including metals, paper, ceramics, etc. The coating involves depositing an ultrasmooth, silicon wafer-like silica layer and then treating this layer with a highly reactive chlorosilane, which grafts polydimethylsiloxane chains onto the surface. Negligible contact angle hysteresis (≤1°) for various liquids, including ultralow surface tension oils, alcohols, and fluoro-solvents, was achieved on many different substrates regardless of their initial roughness or chemistry. In fact, the contact angle hysteresis was so low we were forced to propose an alternate measurement technique, using tilt angles, that reduced the inherent errors associated with traditional contact angle goniometry. The coating's durability was characterized and, when it was damaged, could be repeatedly repaired, fully restoring the omniphobic properties to their initial state.Free energies as a function of a selected set of collective variables are commonly computed in molecular simulation and of significant value in understanding and engineering molecular behavior. These free energy surfaces are most commonly estimated using variants of histogramming techniques, but such approaches obscure two important facets of these functions. First, the empirical observations along the collective variable are defined by an ensemble of discrete observations, and the coarsening of these observations into a histogram bin incurs unnecessary loss of information. Second, the free energy surface is itself almost always a continuous function, and its representation by a histogram introduces inherent approximations due to the discretization. In this study, we relate the observed discrete observations from biased simulations to the inferred underlying continuous probability distribution over the collective variables and derive histogram-free techniques for estimating this free energy surface. We reformulate free energy surface estimation as minimization of a Kullback-Leibler divergence between a continuous trial function and the discrete empirical distribution and show that this is equivalent to likelihood maximization of a trial function given a set of sampled data.