Assessment of Popular DFT and Semiempirical Molecular Orbital Techniques for Calculating Relative Transition State Energies and Kinetic Product Distributions in Enantioselective Organocatalytic Reactions

The performance of computationally accessible levels of calculation for the transition states of organocatalytic reaction has been assessed. Reference post-Hartree–Fock single point energy calculations were used as standards for the gas-phase Born–Oppenheimer relative energies of pairs of alternative transition states that lead to the two product enantiomers. We show that semiempirical methods cannot even be relied on to yield qualitatively correct results. The geometries (optimized, for instance, with DFT) have a large impact on the results of high-level post-HF calculations, so that it is essential to use an adequate DFT technique and basis set. DFT can yield quantitatively correct results that are consistent with post-HF calculations if functionals that consider dispersion are used. Geometries for large systems show larger errors than those for smaller ones but are treated better by functionals such as M06-2X and w97Bxd that include dispersion implicitly or explicitly. Local correlation techniques introduce errors of comparable magnitude to those given by different levels of geometry optimization. We recommend RICC2/TZVP//M06-2X/TZVP, RI-MP2/TZVP// M06-2X/TZVP, and M06-2X/TZVP// M06-2X/TZVP calculations in that order, depending on the size of the system

ROC’n’Ribo: Characterizing a Riboswitching Expression System by Modeling Single-Cell Data

RNA-engineered systems offer simple and versatile control over gene expression in many organisms. In particular, the design and implementation of riboswitches presents a unique opportunity to manipulate any reporter device <i>in cis</i>, executing tight temporal and spatial control at low metabolic costs. Assembled to higher order genetic circuits, such riboswitch-regulated devices may efficiently process logical operations. Here, we propose a hierarchical stochastic modeling approach to characterize an <i>in silico</i> repressor gate based on neomycin- and tetracycline-sensitive riboswitches. The model was calibrated on rich, transient <i>in vivo</i> single-cell data to account for cell-to-cell variability. To capture the effect of this variability on gate performance we employed the well-known ROC-analysis and derived a novel performance indicator for logic gates. Introduction of such a performance measure is necessary, since we aimed to assess the correct functionality of the gate at the single-cell levela prerequisite for its further adaption to a genetic circuitry. Our results may be applied to other genetic devices to analyze their efficiency and ensure their correct performance in the light of cell-to-cell variability

Black TiO₂ Nanotubes: Cocatalyst-Free Open-Circuit Hydrogen Generation

Here we report that TiO₂ nanotube (NT) arrays, converted by a high pressure H₂ treatment to anatase-like “black titania”, show a high open-circuit photocatalytic hydrogen production rate without the presence of a cocatalyst. Tubes converted to black titania using classic reduction treatments (e.g., atmospheric pressure H₂/Ar annealing) do not show this effect. The main difference caused by the high H₂ pressure annealing is the resulting room-temperature stable, isolated Ti³⁺ defect-structure created in the anatase nanotubes, as evident from electron spin resonance (ESR) investigations. This feature, absent for conventional reduction, seems thus to be responsible for activating intrinsic, cocatalytic centers that enable the observed high open-circuit hydrogen generation

Quantitative Metabolomic Profiling of Serum, Plasma, and Urine by ¹H NMR Spectroscopy Discriminates between Patients with Inflammatory Bowel Disease and Healthy Individuals

Serologic biomarkers for inflammatory bowel disease (IBD) have yielded variable differentiating ability. Quantitative analysis of a large number of metabolites is a promising method to detect IBD biomarkers. Human subjects with active Crohn’s disease (CD) and active ulcerative colitis (UC) were identified, and serum, plasma, and urine specimens were obtained. We characterized 44 serum, 37 plasma, and 71 urine metabolites by use of ¹H NMR spectroscopy and “targeted analysis” to differentiate between diseased and non-diseased individuals, as well as between the CD and UC cohorts. We used multiblock principal component analysis and hierarchical OPLS-DA for comparing several blocks derived from the same “objects” (e.g., subject) to examine differences in metabolites. In serum and plasma of IBD patients, methanol, mannose, formate, 3-methyl-2-oxovalerate, and amino acids such as isoleucine were the metabolites most prominently increased, whereas in urine, maximal increases were observed for mannitol, allantoin, xylose, and carnitine. Both serum and plasma of UC and CD patients showed significant decreases in urea and citrate, whereas in urine, decreases were observed, among others, for betaine and hippurate. Quantitative metabolomic profiling of serum, plasma, and urine discriminates between healthy and IBD subjects. However, our results show that the metabolic differences between the CD and UC cohorts are less pronounced

Quantitative Metabolomic Profiling of Serum, Plasma, and Urine by ¹H NMR Spectroscopy Discriminates between Patients with Inflammatory Bowel Disease and Healthy Individuals

Serologic biomarkers for inflammatory bowel disease (IBD) have yielded variable differentiating ability. Quantitative analysis of a large number of metabolites is a promising method to detect IBD biomarkers. Human subjects with active Crohn’s disease (CD) and active ulcerative colitis (UC) were identified, and serum, plasma, and urine specimens were obtained. We characterized 44 serum, 37 plasma, and 71 urine metabolites by use of ¹H NMR spectroscopy and “targeted analysis” to differentiate between diseased and non-diseased individuals, as well as between the CD and UC cohorts. We used multiblock principal component analysis and hierarchical OPLS-DA for comparing several blocks derived from the same “objects” (e.g., subject) to examine differences in metabolites. In serum and plasma of IBD patients, methanol, mannose, formate, 3-methyl-2-oxovalerate, and amino acids such as isoleucine were the metabolites most prominently increased, whereas in urine, maximal increases were observed for mannitol, allantoin, xylose, and carnitine. Both serum and plasma of UC and CD patients showed significant decreases in urea and citrate, whereas in urine, decreases were observed, among others, for betaine and hippurate. Quantitative metabolomic profiling of serum, plasma, and urine discriminates between healthy and IBD subjects. However, our results show that the metabolic differences between the CD and UC cohorts are less pronounced

Quantitative Metabolomic Profiling of Serum, Plasma, and Urine by ¹H NMR Spectroscopy Discriminates between Patients with Inflammatory Bowel Disease and Healthy Individuals

Serologic biomarkers for inflammatory bowel disease (IBD) have yielded variable differentiating ability. Quantitative analysis of a large number of metabolites is a promising method to detect IBD biomarkers. Human subjects with active Crohn’s disease (CD) and active ulcerative colitis (UC) were identified, and serum, plasma, and urine specimens were obtained. We characterized 44 serum, 37 plasma, and 71 urine metabolites by use of ¹H NMR spectroscopy and “targeted analysis” to differentiate between diseased and non-diseased individuals, as well as between the CD and UC cohorts. We used multiblock principal component analysis and hierarchical OPLS-DA for comparing several blocks derived from the same “objects” (e.g., subject) to examine differences in metabolites. In serum and plasma of IBD patients, methanol, mannose, formate, 3-methyl-2-oxovalerate, and amino acids such as isoleucine were the metabolites most prominently increased, whereas in urine, maximal increases were observed for mannitol, allantoin, xylose, and carnitine. Both serum and plasma of UC and CD patients showed significant decreases in urea and citrate, whereas in urine, decreases were observed, among others, for betaine and hippurate. Quantitative metabolomic profiling of serum, plasma, and urine discriminates between healthy and IBD subjects. However, our results show that the metabolic differences between the CD and UC cohorts are less pronounced