ACS Combinatorial Science最新文献

Establishing synthesis methods for a target material constitutes?a grand challenge in materials research, which is compounded with use-inspired specifications on the format of the material. Solar photochemistry using thin film materials is a promising technology for which many complex materials are being proposed, and the present work describes application of combinatorial methods to explore the synthesis of predicted La–Bi–Cu oxysulfide photocathodes, in particular alloys of LaCuOS and BiCuOS. The variation in concentration of three cations and two anions in thin film materials, and crystallization thereof, is achieved by a combination of reactive sputtering and thermal processes including reactive annealing and rapid thermal processing. Composition and structural characterization establish composition-processing-structure relationships that highlight the breadth of processing conditions required for synthesis of LaCuOS and BiCuOS. The relative irreducibility of La oxides and limited diffusion indicate the need for high temperature processing, which conflicts with the temperature limits for mitigating evaporation of Bi and S. Collectively the results indicate that alloys of these phases will require reactive annealing protocols that are uniquely tailored to each composition, motivating advancement of dynamic processing capabilities to further automate discovery of synthesis routes.

The Cr–Co–Ni system was studied by combining experimental and computational methods to investigate phase stability and mechanical properties. Thin-film materials libraries were prepared and quenched from high temperatures up to 700 °C using a novel quenching technique. It could be shown that a wide A1 solid solution region exists in the Cr–Co–Ni system. To validate the results obtained using thin-film materials libraries, bulk samples of selected compositions were prepared by arc melting, and the experimental data were additionally compared to results from DFT calculations. The computational results are in good agreement with the measured lattice parameters and elastic moduli. The lattice parameters increase with the addition of Co and Cr, with a more pronounced effect for the latter. The addition of ～20 atom % Cr results in a similar hardening effect to that of the addition of ～40 atom % Co.

In this research, machine learning including the genetic algorithm (GA) and support vector machine (SVM) algorithm is used to solve the “low up-conversion luminescence (UCL) intensity” problem in order to find the optimal phosphor with enhanced red UCL emission using multielement K/Li/Mn metal modulation. Compared with the first generation of phosphors, the best phosphors’ fluorescence intensity occurs in the third generation optimized by the GA, with a stronger brightness (4.91-fold), a higher relative quantum yield (6.40-fold), and an enhanced tissue penetration depth (by 5 mm). The single and multiple dopants effect on the upconversion intensity of K+Li+Mn sensitizers is also studied: the intensity increases first and then decreases with the increase of Yb/Er/K+Li+Mn content, and the optimized K+Li+Mn concentration is 6.03%. In order to confirm the stability of the brightness optimization by the GA, a batch of phosphors was synthesized with the same element proportion, and the similarity of fluorescence intensity of two batches of phosphors was evaluated by the SVM algorithm with the classification accuracy index. Finally, the optimized phosphor was used for bioimaging and phosphor-LED.

Through a screen of over one hundred and 30 permutations of reaction temperatures, solvents, carbodiimide resins, and carbodiimide molar equivalences, in the presence, absence, or combination of diisopropylamine and benzotriazole additives, a convenient and first reported carbodiimide polymer-assisted flow approach to effect amide coupling and lactamization was developed. The protocol entails injecting a single solution (1:9 dimethylformamide: dichloromethane) containing a carboxylic acid and an amine or linear peptide sequence into a continuous stream of dichloromethane. The protocol remained viable in the absence of base, did not require carboxylate preactivation which, and in concert with minimal workup requirements, enabled the isolation of products in high yields. Compared to the utilization of untethered carbodiimide reagents, the flow procedure was also observed to provide a degree of racemization safety.

Yeast surface display empowers selection of protein binding ligands, typically using recombinant soluble antigens. However, ectodomain fragments of transmembrane targets may fail to recapitulate their true, membrane-bound form. Direct selections against adhered mammalian cells empower enrichment of genuine binders yet benefit from high target expression, robustly adherent mammalian cells, and nanomolar affinity ligands. This study evaluates a modified format with mammalian cells immobilized to magnetic beads; yeast-displayed fibronectin domain and affibody ligands of known affinities and cells with expression ranges of epidermal growth factor receptor (EGFR) and CD276 elucidate important parameters to ligand enrichment and yield in cell suspension panning with comparison to adherent panning. Cell suspension panning is hindered by significant background of nondisplaying yeast but exhibits yield advantages in model EGFR systems for a high affinity (K_D = 2 nM) binder on cells with both high (10⁶ per cell) target expression (9.6 ± 0.6% vs 3.2 ± 0.4%, p < 0.0001) and mid (10⁵) target expression (2.3 ± 0.5% vs 0.41 ± 0.09%, p = 0.0008), as well as for a low affinity (K_D > 600 nM) binder on high target expression cells (2.0 ± 0.5% vs 0.017 ± 0.005%; p = 0.001). Significant enrichment was observed for all EGFR systems except the low-affinity, high expression system. The CD276 system failed to provide significant enrichment, indicating that this technique may not be suitable for all targets. Collectively, this study highlights new approaches that yield successful enrichment of yeast-displayed ligands via panning on immobilized mammalian cells.

Cerium(III) triflate-catalyzed multicomponent reactions between alkynyl carboxylic acids, tert-butyl isocyanide, and organic azides have been developed. In the presence of Ce(OTf)₃ (10 mol %), the cascade reaction of one molecule of alkynyl carboxylic acid with three molecules of tert-butyl isocyanides proceeds chemoselectively and regioselectively via a triple and ordered isocyanide insertion process at room temperature, and then the cesium-catalyzed [3 + 2] cycloaddtion reaction between the resulted alkynyl oxazole and organic azides was further initiated by the temperature elevation (100 °C), thereby leading to multisubstituted triazole–oxazole derivatives in practical, time-saving, one-pot operations. Furthermore, some of the synthesized target compounds showed potential anticancer activities against MGC803 (human gastric cancer cell) with IC₅₀ values below 20 μmol L^–1.

Adleman’s illustration of molecular computing using DNA paved the way toward an entirely new direction of computing (Adleman, L. M. Science 1994, 266, 1021). The exponential time complex combinatorial problem on a traditional computer turns out to be a separation problem involving a polynomial number of steps in DNA computing experiments. Despite being a promising concept, the implementations of existing DNA computing procedures were restricted only to the smaller size formulations. In this work, we demonstrate a structure assisted DNA computing procedure on a bigger size Hamiltonian cycle problem involving 18 vertices. The developed model involves the formation and digestion of circular structure DNA, iteratively over multiple stages to eliminate the incorrect solutions to the given combinatorial problem. A high accuracy is obtained compared to other structure assisted models, which enable one to solve the bigger size problems.

Efficient and precise construction of DNA libraries is a fundamental starting point for directed evolution of polypeptides. Recently, several in vitro selection methods have been reported that do not rely on cells for protein expression, where peptide libraries in the order of 10¹³ species are used for in vitro affinity selection. To maximize their potential, simple yet versatile construction of DNA libraries from several fragments containing random regions without bacterial transformation is essential. To address this issue, we herein propose a novel DNA construction methodology based on the use of polymerase chain reaction (PCR) primers containing a single deoxyinosine (I) residue near their 5′ end. Treatment of the PCR products with endonuclease V generates 3′ overhangs with customized lengths and sequences, which can be ligated accurately and efficiently with other fragments having exactly complementary overhangs. As a proof of concept, we constructed an artificial gene library of single-domain antibodies from four DNA fragments.

Additive manufacturing synthesis using laser engineered net shaping (LENS) is utilized to rapidly print libraries of mischmetal (MM = La, Ce, Nd, and Pr) containing R₂TM₁₄B alloys (R = MM + separated Nd and TM = Fe and Co) enabling robust evaluation of physical properties over a wide composition range. High-throughput characterization of the magnetic and thermal properties are used to identify compositions for potential high-temperature, high-performance permanent magnets with reduced critical rare-earth elements. Improved Curie temperature (T_c ～ 450 °C) is obtained with substitution of Fe by Co in pseudoternary R₂TM₁₄B alloys. Furthermore, a 4-fold decrease in the Nd content can be achieved through substitution with less critical Ce- and La-rich MM, while retaining high T_c. Guided by the properties of the LENS printed samples, selected compositions with and without TiC additions are synthesized via melt-spinning techniques to produce nanostructured ribbons. The maximum room temperature coercivity (H_c) and energy product ((BH)_max) without TiC are found to be 5.8 kOe, 8.5 MGOe, respectively, while TiC additions as a grain refiner gave H_c and (BH)_max of 4.9 kOe, 9.8 MGOe, respectively. Structural characterization of the melt-spun ribbons shows homogeneous grain refinement with TiC additions, which leads to an increase in the energy product.