Noble-Metal Substitution in Hemoproteins: An Emerging Strategy for Abiological Catalysis.

Enzymes have evolved to catalyze a range of biochemical transformations with high efficiencies and unparalleled selectivities, including stereoselectivities, regioselectivities, chemoselectivities, and substrate selectivities, while typically operating under mild aqueous conditions. These properties have motivated extensive research to identify or create enzymes with reactivity that complements or even surpasses the reactivity of small-molecule catalysts for chemical reactions. One of the limitations preventing the wider use of enzymes in chemical synthesis, however, is the narrow range of bond constructions catalyzed by native enzymes. One strategy to overcome this limitation is to create artificial metalloenzymes (ArMs) that combine the molecular recognition of nature with the reactivity discovered by chemists. This Account describes a new approach for generating ArMs by the formal replacement of the natural iron found in the porphyrin IX (PIX) of hemoproteins with noble metals. Analytical techniques coupled with studies of chemical reactivity have demonstrated that expression of apomyoglobins and apocytochrome P450s (for which "apo-" denotes the cofactor-free protein) followed by reconstitution with metal-PIX cofactors in vitro creates proteins with little perturbation of the native structure, suggesting that the cofactors likely reside within the native active site. By means of this metal substitution strategy, a large number of ArMs have been constructed that contain varying metalloporphyrins and mutations of the protein. The studies discussed in this Account encompass the use of ArMs containing noble metals to catalyze a range of abiological transformations with high chemoselectivity, enantioselectivity, diastereoselectivity, and regioselectivity. These transformations include intramolecular and intermolecular insertion of carbenes into C-H, N-H, and S-H bonds, cyclopropanation of vinylarenes and of internal and nonconjugated alkenes, and intramolecular insertions of nitrenes into C-H bonds. The rates of intramolecular insertions into C-H bonds catalyzed by thermophilic P450 enzymes reconstituted with an Ir(Me)-PIX cofactor are now comparable to the rates of reactions catalyzed by native enzymes and, to date, 1000 times greater than those of any previously reported ArM. This reactivity also encompasses the selective intermolecular insertion of the carbene from ethyl diazoacetate into C-H bonds over dimerization of the carbene to form alkenes, a class of carbene insertion or selectivity not reported to occur with small-molecule catalysts. These combined results highlight the potential of well-designed ArMs to catalyze abiological transformations that have been challenging to achieve with any type of catalyst. The metal substitution strategy described herein should complement the reactivity of native enzymes and expand the scope of enzyme-catalyzed reactions

Average causal effect estimation via instrumental variables: the no simultaneous heterogeneity assumption

Instrumental variables (IVs) can be used to provide evidence as to whether a treatment X has a causal effect on Y. Z is a valid instrument if it satisfies the three core IV assumptions of relevance, independence and the exclusion restriction. Even if the instrument satisfies these assumptions, further assumptions are required to estimate the average causal effect (ACE) of X on Y. Sufficient assumptions for this include: homogeneity in the causal effect of X on Y; homogeneity in the association of Z with X; and No Effect Modification (NEM). Here, we describe the NO Simultaneous Heterogeneity (NOSH) assumption, which requires the heterogeneity in the X-Y causal effect to be independent of both Z and heterogeneity in the Z-X association. We describe the necessary conditions for NOSH to hold, in which case conventional IV methods are consistent for the ACE even if both homogeneity assumptions and NEM are violated. We illustrate these ideas using simulations and by re-examining selected published studies

Representations of hom-Lie algebras

In this paper, we study representations of hom-Lie algebras. In particular, the adjoint representation and the trivial representation of hom-Lie algebras are studied in detail. Derivations, deformations, central extensions and derivation extensions of hom-Lie algebras are also studied as an application.Comment: 16 pages, multiplicative and regular hom-Lie algebras are used, Algebra and Representation Theory, 15 (6) (2012), 1081-109

Machine learning detects multiplicity of the first stars in stellar archaeology data

In unveiling the nature of the first stars, the main astronomical clue is the elemental compositions of the second generation of stars, observed as extremely metal-poor (EMP) stars, in our Milky Way Galaxy. However, no observational constraint was available on their multiplicity, which is crucial for understanding early phases of galaxy formation. We develop a new data-driven method to classify observed EMP stars into mono- or multi-enriched stars with Support Vector Machines. We also use our own nucleosynthesis yields of core-collapse supernovae with mixing-fallback that can explain many of observed EMP stars. Our method predicts, for the first time, that $31.8\% \pm 2.3\%$ of 462 analyzed EMP stars are classified as mono-enriched. This means that the majority of EMP stars are likely multi-enriched, suggesting that the first stars were born in small clusters. Lower metallicity stars are more likely to be enriched by a single supernova, most of which have high carbon enhancement. We also find that Fe, Mg. Ca, and C are the most informative elements for this classification. In addition, oxygen is very informative despite its low observability. Our data-driven method sheds a new light on solving the mystery of the first stars from the complex data set of Galactic archaeology surveys.Comment: Accepted by ApJ, main results in Fig. 5, source code is available at https://gitlab.com/thartwig/emu-

The star partial order and the eigenprojection at 0 on EP matrices

[EN] The space of n x n complex matrices with the star partial order is considered in the first part of this paper. The class of EP matrices is analyzed and several properties related to this order are given. In addition, some information about predecessors and successors of a given EP matrix is obtained. The second part is dedicated to the study of some properties that relate the eigenprojection at 0 with the star and sharp partial orders. 2012 Elsevier Inc. All rights reserved.This paper was partially supported by Ministry of Education of Argentina (PPUA, Grant Resol. 228, SPU, 14-15-222) and by Universidad Nacional de La Pampa, Facultad de Ingenieria (Grant Resol. No 049/11).Hernández, AE.; Lattanzi, MB.; Thome, N.; Urquiza, F. (2012). The star partial order and the eigenprojection at 0 on EP matrices. Applied Mathematics and Computation. 218(21):10669-10678. https://doi.org/10.1016/J.AMC.2012.04.034S10669106782182

Site-Selective Functionalization of (sp3 )C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor.

The selective functionalization of one C-H bond over others in nearly identical steric and electronic environments can facilitate the construction of complex molecules. We report site-selective functionalizations of C-H bonds, differentiated solely by remote substituents, catalyzed by artificial metalloenzymes (ArMs) that are generated from the combination of an evolvable P450 scaffold and an iridium-porphyrin cofactor. The generated systems catalyze the insertion of carbenes into the C-H bonds of a range of phthalan derivatives containing substituents that render the two methylene positions in each phthalan inequivalent. These reactions occur with site-selectivity ratios of up to 17.8:1 and, in most cases, with pairs of enzyme mutants that preferentially form each of the two constitutional isomers. This study demonstrates the potential of abiotic reactions catalyzed by metalloenzymes to functionalize C-H bonds with site selectivity that is difficult to achieve with small-molecule catalysts