Dissolved organic matter (DOM) plays a significant role in the transport and transformation of pollutants in the aquatic environment. However, the experimental characterization of DOM has been limited mainly to bulk properties, and the molecular-level interactions among various components of DOM remain to be fully characterized. Here, we use molecular dynamics (MD) simulations to probe the structural properties of model DOM systems at atomic detail. The 200 ns simulations, validated by available experimental data, reveal processes and mechanisms by which chemical species (cations, peptides, lipids, lignin, carbohydrates, and some low-molecular-weight aliphatic and aromatic compounds) aggregate to form complex DOM. The DOM aggregates are dynamic, consisting of a hydrophobic core and amphiphilic exterior. The lipid tails and other hydrophobic fragments form the core, with hydrophilic and amphiphilic groups exposed to water, making DOM accessible to both polar and nonpolar species. Thus, the lipid component acts as a nucleator, whereas cations (especially Ca2+) connect the molecular fragments on the surface by coordinating with the O-containing functional groups of DOM. The structural details revealed here provide new insights including surface accessible atoms, overall assemblage, and interactions among the molecules of DOM for understanding the kinetics and mechanisms through which DOM interacts with metal and other contaminants.

BOOK

To assess the chemical reactivity, toxicity, and mobility of pollutants in the environment, knowledge of their species distributions is critical. Because their direct measurement is often infeasible, speciation modeling is widely adopted. Mercury (Hg) is a representative pollutant for which study of its speciation benefits from modeling. However, Hg speciation modeling is often hindered by a lack of reliable thermodynamic constants. Although computational chemistry (e.g., density functional theory [DFT]) can generate these constants, methods for directly coupling DFT and speciation modeling are not available. Here, we combine computational chemistry and continuum-scale modeling with curated online databases to ameliorate the problem of unreliable inputs to Hg speciation modeling. Our AQUA-MER databases and web server (https://aquamer.ornl.gov) provides direct speciation results by combining web-based interfaces to a speciation calculator, databases of thermodynamic constants, and a computational chemistry toolkit to estimate missing constants. Although Hg is presented as a concrete use case, AQUA-MER can also be readily applied to other elements. © 2019 Wiley Periodicals, Inc.

Stability constants are central to the multiscale modeling of the thermodynamic speciation, cycling, and transport of mercury (Hg) and other contaminants in aquatic environments. However, for Hg, experimental values for many relevant complexes are not available, and for others can span ranges in excess of 10 log units. The missing data and large uncertainties lead to significant knowledge gaps in predictions of thermodynamic speciation. As an alternative to experimental measurements, thermodynamic quantities can be calculated with quantum chemical methods. Among these, density functional theory (DFT) with a polarizable continuum solvent combines accuracy with practicability. Here, we present an accurate and quick approach in which we use DFT with continuum solvation to calculate stability constants of Hg complexes with inorganic and low molecular-weight organic ligands in aqueous solution. Specifically, we use the M06/ [SDD]6-31+G(d,p) level of theory in combination with a modified version of the SMD solvent model in which the solute radii are reoptimized with a scaled solvent-accessible surface approach. For the set of 37 Hg complexes used for optimization, which contain environmentally relevant functional groups and have reliable experimental stability constants, we obtain a mean unsigned error of 1.4 log units. Testing the method on an independent set of 12 Hg complexes reproduces the experimental stability constants to a mean unsigned error of 1.6 log units. This approach is a substantial step toward generally applicable rapid stability constant derivation for a wide range of Hg complexes, including those present in dissolved organic matter.

The properties of disordered proteins are thought to depend on intrinsic conformational propensities for polyproline II (PP II) structure. While intrinsic PP II propensities have been measured for the common biological amino acids in short peptides, the ability of these experimentally determined propensities to quantitatively reproduce structural behavior in intrinsically disordered proteins (IDPs) has not been established. Presented here are results from molecular simulations of disordered proteins showing that the hydrodynamic radius (R h) can be predicted from experimental PP II propensities with good agreement, even when charge-based considerations are omitted. The simulations demonstrate that R h and chain propensity for PP II structure are linked via a simple power-law scaling relationship, which was tested using the experimental R h of 22 IDPs covering a wide range of peptide lengths, net charge, and sequence composition. Charge effects on R h were found to be generally weak when compared to PP II effects on R h. Results from this study indicate that the hydrodynamic dimensions of IDPs are evidence of considerable sequence-dependent backbone propensities for PP II structure that qualitatively, if not quantitatively, match conformational propensities measured in peptides.

1-Diphenylphosphinonaphthyl-8-triphenylstibonium triflate ([][OTf]) was prepared in excellent yield by treating 1-lithio-8-diphenylphosphinonaphthalene with dibromotriphenylstiborane followed by halide abstraction with AgOTf. This antimony(v) cation was found to be stable toward oxygen and water, and exhibited exceptional Lewis acidity. The Lewis acidity of [][OTf] was exploited in the catalytic reductive coupling of a variety of aldehydes into symmetric ethers of type in good to excellent yields under mild conditions using Et3SiH as the reductant. Additionally, [][OTf] was found to selectively catalyze the Aldol condensation reaction to afford α-β unsaturated aldehydes () when aldehydes with 2 α-hydrogen atoms were used. Finally, [][OTf] catalyzed the cyclotrimerization of aliphatic and aromatic aldehydes to afford the industrially-useful 1,3,5 trioxanes () in good yields, and with great selectivity. This phosphine-stibonium motif represents one of the first catalytic systems of its kind that is able to catalyze these reactions with aldehydes in a controlled, efficient manner. The mechanism of these processes has been explored both experimentally and theoretically. In all cases the Lewis acidic nature of the antimony(v) cation was found to promote these reactions.

Methane conversion to methyl bisulfate by Hg-II(SO4) in sulfuric acid is an example of fast and selective alkane oxidation catalysis. Dichotomous mechanisms involving C-H activation and electron transfer have been proposed based on experiments. Radical oxidation pathways have also been proposed for some reaction conditions. Hg-II is also of significant interest because as a d(10) transition metal it is similar to d(10) main-group metals that also oxidize alkanes. Density functional calculations are presented that use both implicit and a mixture of implicit/explicit solvent models for the complete Hg-II catalytic cycle of methane oxidation to methyl bisulfate. These calculations are consistent with experiment and reveal that methane is functionalized to methyl bisulfate by a C-H activation and reductive metal alkyl functionalization mechanism. This reaction pathway is lower in energy than both electron transfer and proton-coupled electron transfer pathways. After methane C-H functionalization, catalysis is completed by conversion of the proposed resting state, [Hg-I(HSO4)](2), into Hg-0 followed by Hg-0 to Hg-II oxidation induced by SO3 from dehydration of sulfuric acid. This catalytic cycle is efficient because in sulfuric acid the Hg-II/Hg-0 potential results in a moderate free energy barrier for oxidation (similar to 40 kcal/mol) and Hg-II is electrophilic enough to induce barriers of <40 kcal/mol for C-H activation and reductive metal alkyl functionalization. Comparison of Hg-II to Tl-III shows that while C-H activation and reductive metal alkyl functionalization have reasonable barriers for Tl-III, the oxidation of Tl-I to Tl-III has a significantly larger barrier than Hg-0 to Hg-II oxidation and therefore Tl-III is not catalytic in sulfuric acid. Comparison of Hg-II to Cd-II and Zn-II reveals that while M-0 to M-II oxidation and C-H activation are feasible for these first-row and second-row transition metals, reductive metal alkyl functionalization barriers are very large and catalysis is not feasible. Calculations are also presented that outline the mechanism and energy landscape for radical-initiated (K2S2O8) methane oxidation to methanesulfonic acid in sulfuric acid.

Heteroaromatic azadienes, especially 1,2,4,5-tetrazines, are extremely reactive partners with alkenes in inverse-electron-demand Diels-Alder reactions. Azadiene cycloaddition reactions are used to construct heterocycles in synthesis and are popular as bioorthogonal reactions. The origin of fast azadiene cycloaddition reactivity is classically attributed to the inverse frontier molecular orbital (FMO) interaction between the azadiene LUMO and alkene HOMO. Here, we use a combination of ab initio, density functional theory, and activation-strain model calculations to analyze physical interactions in heteroaromatic azadiene-alkene cycloaddition transition states. We find that FMO interactions do not control reactivity because, while the inverse FMO interaction becomes more stabilizing, there is a decrease in the forward FMO interaction that is offsetting. Rather, fast cycloadditions are due to a decrease in closed-shell Pauli repulsion between cycloaddition partners. The kinetic-thermodynamic relationship found for these inverse-electron-demand cycloadditions is also due to the trend in closed-shell repulsion in the cycloadducts. Cycloaddition regioselectivity, however, is the result of differences in occupied-unoccupied orbital interactions due to orbital overlap. These results provide a new predictive model and correct physical basis for heteroaromatic azadiene reactivity and regioselectivity with alkene dieneophiles.

Activation and functionalization of alkane C-H bonds has historically been dominated by transition-metal complexes. Light alkanes can also be partially oxidized by sixth-row main-group compounds, such as Tl-III(TFA)(3) (TFA = trifluoroacetate). Here ive present density-functional calculations which demonstrate that Tl-III(TFA)(3) oxidizes alkanes by closed-shell C-H activation and Tl-alkyl functionalization mechanisms. The discovery of a CH activation pathway is surprising, because Tl-III often oxidizes arene C-H bonds through an electron transfer mechanism and the transitionmetal complex Co-III(TFA)(3), with similar oxidation state and ligand coordination, oxidizes alkanes via an open-shell radical mechanism. Comparison of Tl-III(TFA)(3) to the transition-metal analogue Ir-III(TFA)(3) reveals that key to Tl-III oxidation of alkanes is a moderate barrier for C-H bond activation that is lower in energy than open-shell pathways and a subsequent metal alkyl functionalization reaction step with a very low barrier. Our calculations suggest that the high-spin ground state of Co-III(TFA)(3) provides a low-energy open-shell decarboxylation pathway that leads to radical oxidation of alkanes, which is not available for the d(10) Tl-III(TTFA)(3) complex. The C-H activation pathway and transition state model provide a straightforward explanation for why Tl-III(TFA)(3) promotes alkane C-H bond activation but Hg-II(TFA)(2) does not.

Despite the prevalence of the N-H aziridine motif in bioactive natural products and the clear advantages of this unprotected parent structure over N-protected derivatives as a synthetic building block, no practical methods have emerged for direct synthesis of this compound class from unfunctionalized olefins. Here, we present a mild, versatile method for the direct stereospecific conversion of structurally diverse mono-, di-, triand tetra-substituted olefins to NH aziridines using O-(2,4-dinitrophenyl)hydroxylamine (DPH) via homogeneous rhodium catalysis with no external oxidants. This method is operationally simple (i.e., one-pot), scalable and fast at ambient temperature, furnishing N-H aziridines in good-to-excellent yields. Likewise, N-alkyl aziridines are prepared from N-alkylated DPH derivatives. Quantum-mechanical calculations suggest a plausible Rh-nitrene pathway. Aziridines, the triangular, comparably highly-strained nitrogen analogues of epoxides, are important synthetic intermediates (i.e., building blocks) en route to structurally complex molecules due to their versatility in myriad regioand stereoselective transformations (ring openings and expansions as well as rearrangements).(1–6) The aziridine structural motif, predominantly N-H and to a lesser extent N-alkyl, also appears in biologically active natural products (e.g., azinomycins and mitomycins).(7–9) As a result, the synthesis and chemistry of aziridines have been the subject of intense research during the past 25 years, resulting in multiple aziridination methods.(10–23) The majority of these methods rely either on the transfer of substituted nitrenes, which are generated using strong external oxidants, to the C=C bond of olefins or the transfer of substituted carbenes to the C=N bond of imines. Normally, the result is an aziridine bearing a strongly electron-withdrawing N-protecting group (e.g., Ts = para-toluenesulfonyl, Ns = para-nitrophenylsulfonyl); removal of these Nsulfonyl protecting groups is problematic as it often results in the undesired opening of the Author notes: Authors marked with ‘*’ have contributed equally to this work. Supplementary Materials: Materials and Methods Figures S1a–S1f, S2a & S2b, S3a–S3c, S4a & S4b, S5 Tables S1–S3, S4–S6, S7–S8 NIH Public Access Author Manuscript Science. Author manuscript; available in PMC 2014 September 25. Published in final edited form as: Science. 2014 January 3; 343(6166): 61–65. doi:10.1126/science.1245727. N IH -P A A uhor M anscript N IH -P A A uhor M anscript N IH -P A A uhor M anscript aziridine ring. In addition, the high reactivity of N-protected nitrenes might give rise to nonproductive allylic C-H amination products as well as the loss of stereospecificity. Clearly, the direct synthesis of N-H (i.e., N-unprotected) and N-alkyl aziridines would alleviate the above problems. However, a practical, functional group-tolerant and environmentally benign direct preparation of N-H aziridines from structurally diverse olefins has so far eluded synthetic chemists.(24–31) Herein, we report an operationally simple, inherently safe, chemoselective and stereospecific conversion of a wide range of olefins to the corresponding N-H/N-Me aziridines via a rhodium-catalyzed pathway free of external oxidants. Recently, we developed a metal-free protocol for primary amination of arylboronic acids using only O-(2,4-dinitrophenyl)hydroxylamine (DPH, 1a, Fig. 1) as the stoichiometric aminating agent.(32) The transformation proceeds under neutral or basic conditions and can be conducted on a multi-gram scale to provide structurally diverse primary arylamines. The versatility and robustness of 1a prompted us to explore other uses of this aminating agent, specifically for the direct functionalization of readily available and inexpensive olefins. Our investigations began by subjecting 1:1.5 mixtures of cis-methyl oleate (7)/1a as well as styrenes (3a & 3b)/1a to a vigorous screening with a variety of transition metal complexes (see Tables S1 & S2, Supplementary Materials). This initial screen identified Rh2(OAc)4 as a promising catalyst for vic-amino-oxyarylation of olefins. Further evaluation of dimeric rhodium dicarboxylate complexes (see Table S3, Supplementary Materials), revealed that just 1 mol% loading of Du Bois’ catalyst(33–36) (2, Fig. 1) in acetonitrile (MeCN) leads to amino-oxyarylated styrenes 4a and 4b at room temperature in 56% and 75% isolated yields, respectively. These promising results prompted us to conduct a thorough solvent screen. In methanol, we observed the incorporation of the MeO group at the benzylic position (5) in addition to the amino-oxyarylated product 4b; these compounds were isolated in a combined yield of 78%. At this juncture, we reasoned a highly polar, hydroxylic and non-nucleophilic solvent such as 2,2,2-trifluoroethanol (CF3CH2OH, TFE) would completely avoid the incorporation of solvent into the products. Indeed, 3b was cleanly amino-oxyarylated in TFE and 4b was isolated in 66% yield. It was unclear if the transformation 3b→4b involved the opening of a highly reactive aziridine (6) or an alternative process. Surprisingly, when 7 was reacted in trifluoroethanol as solvent, cis-N-H aziridine 8 was isolated in excellent yield (83%) instead of the expected amino-oxyarylated product. The transformation proceeded with complete stereospecificity as no traces of the trans-N-H aziridine were detected by 1Hand 13C-NMR analysis (2% sensitivity). Encouraged by this unexpected, yet most welcome result, a systematic study was initiated using representative aliphatic olefins with a wide range of substitution patterns and functionalities (Fig. 2). Terminal aliphatic olefin substrates (entries 1–3, Fig. 2) either did not react or reacted sluggishly (i.e., days) when 1 mol% of catalyst 2 was used; however, increasing the catalyst loading to 5 mol% led to rapid conversion at room temperature to the corresponding N-H aziridines (10a–c). We empirically found that in some of the reactions (i.e., entries 4, 5, 7, 9, 11, 14 & 20) addition of the catalyst in several 1 mol% portions minimized decomposition of both the catalyst and aminating agent and invariably led to higher isolated yield of product. Remarkably, the N-H aziridination took place efficiently in Jat et al. Page 2 Science. Author manuscript; available in PMC 2014 September 25. N IH -P A A uhor M anscript N IH -P A A uhor M anscript N IH -P A A uhor M anscript the presence of a labile terminal epoxide (10c) as well as an unprotected primary alcohol (10a); these functionalities typically interfere with currently used aziridination protocols. In case of the transformation 9c→10c, only the product was detected in the crude reaction mixture by NMR analysis. In the presence of 1 mol% of catalyst 2, both cisand trans-1,2disubstituted aliphatic olefins (entries 4–10, Fig. 2) underwent smooth and stereospecific NH aziridination at room temperature as established by 13C-NMR analysis (≤2% sensitivity). The presence of an unprotected secondary alcohol in substrate 9i (entry 9) did not influence the stereochemical outcome of the N-H aziridination and 10i was isolated as a 1:1 mixture of diastereomers. Benzoyloxy and acetyloxy cis-olefins 9k and 9m (entries 11 & 14), when exposed to 1 mol % of catalyst 2 and 1.2 equiv of aminating agent 1a at 50 °C, were smoothly aziridinated followed by an in situ aziridine ring-opening (via transacylation) to yield the corresponding trans-2,3-disubstituted furans 10kk and 10mm in 84% and 61% yields, respectively. On the other hand, when olefin 9k was exposed to 5 mol% loading of catalyst 2 and 1.2 equivalents of 1a at 25 °C, the expected N-H aziridine 10k (entry 12) was formed in just 2 hours and isolated in 69% yield. As anticipated, when the rate of N-H aziridination is slow and elevated temperatures are used, secondary processes (i.e., intramolecular annulation) that consume the initially formed N-H aziridines can dominate. Apparently, a five-fold increase in catalyst loading increased the rate of N-H aziridination sufficiently that it could take place rapidly at ambient temperature. Cyclohexene 9n (entry 15) was aziridinated at room temperature to afford cyclic N-H aziridine 10n; no traces of allylic C-H amination (i.e., 1-amino-2-cyclohexene) could be detected by 1H-NMR analysis (2% sensitivity), in sharp contrast with other metal nitrenebased aziridination methods.(37) Geraniol (9o, entry 16) and geranyl acetate (9q, entry 18), which incorporate two trisubstituted C=C double bonds, were N-H aziridinated regioselectively, favoring the double bond at the Δ6,7-position over the Δ2,3-position in both cases. The shift of the regioisomeric ratio from 1:5 in 10o to 1:14 in 10q suggests a subtle directing effect of the free allylic alcohol and/or an inductive deactivation by the acetate; perhaps the extent of H-bonding in the solvent also plays a role. Entry 17 stands as a testament to the extraordinarily mild reaction conditions as trisubstituted olefin 9p, which possesses a highly sensitive epoxy alcohol, was aziridinated rapidly and efficiently to epoxy N-H aziridine 10p in excellent yield. The transformation 9q→10q (entry 18) could be readily scaled up (6 mmol) with minimal erosion of the isolated yield to provide gram quantities of 10q. N-H aziridination of limonene 9r (entry 19) favored the trisubstituted ring double bond with 9:1 regioselectivity; however, the chiral center had no evident influence on the diastereoselectivity (1:1 dr). In contrast with the lack of stereoselectivity in 9i, cholesterol 9s (entry 20) exclusively yielded the β-N-H aziridine 10s in 71% yield; this unexpected stereochemical outcome, confirmed by single crystal X-ray analysis of 10ss (a crystalline derivative of 10s), suggests a directing effect by the adjacent C(3)-β-alcohol not observed in conformationally more mobile acyclic molecules such as 9i. The success with cholesterol and other natural products (7, 9h, 9i, 9o

Direct partial oxidation of methane, ethane, and propane to their respective trifluoroacetate esters is achieved by a homogeneous hypervalent iodine(III) complex in non-superacidic (trifluoroacetic acid) solvent. The reaction is highly selective for ester formation (>99%). In the case of ethane, greater than 0.5 M EtTFA can be achieved. Preliminary kinetic analysis and density functional calculations support a nonradical electrophilic CH activation and iodine alkyl functionalization mechanism.

The Rh(III) complexes [((t)bpy)2Rh(OMe)(L)][X]n ((t)bpy = 4,4'-di-tert-butyl-2,2'-bipyridyl; L = MeOH, n = 2, X = OTf (OTf = trifluoromethanesulfonate), TFA (TFA = trifluoroacetate); L = TFA, n = 1, X = OTf) have been shown to activate dihydrogen via net 1,2-addition of the H-H bond across the Rh(III)-OMe bond. The bis(methoxide) complex [((t)bpy)2Rh(OMe)2][OTf] was synthesized by addition of CsOH·H2O in methanol to [((t)bpy)2Rh(OTf)2][OTf] in CH3CN. The addition of HTFA to [((t)bpy)2Rh(OMe)2][OTf] leads to the formation of [((t)bpy)2Rh(OMe)(MeOH)][OTf][TFA], which exists in equilibrium with [((t)bpy)2Rh(OMe)(TFA)][OTf]. The mixture of [((t)bpy)2Rh(OMe)(MeOH)][OTf][TFA] and [((t)bpy)2Rh(OMe)(TFA)][OTf] activates dihydrogen at 68 °C to give methanol and [((t)bpy)2Rh(H)(TFA)][OTf]. Studies indicate that the activation of dihydrogen has a first-order dependence on the Rh(III) methoxide complex and a dependence on hydrogen that is between zero and first order. Combined experimental and computational studies have led to a proposed mechanism for hydrogen activation by [((t)bpy)2Rh(OMe)(MeOH)][OTf][TFA] that involves dissociation of MeOH, coordination of hydrogen, and 1,2-addition of hydrogen across the Rh-OMe bond. DFT calculations indicate that there is a substantial energy penalty for MeOH dissociation and a relatively flat energy surface for subsequent hydrogen coordination and activation.

AbstractThis method gives unprotected aziridines from mono‐, di‐, tri‐ and tetrasubstituted olefins in good yields.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Undergraduate organic chemistry textbooks and Internet websites use a variety of approaches for presenting and explaining the impact of halogen atom size on trends in bond strengths and/or acidity of hydrogen halides. In particular, several textbooks and Internet websites explain these trends by invoking decreasing orbital overlap between the hydrogen is atomic orbital and successively larger group 17 halogen atomic orbitals. A similar orbital overlap rationalization is often extended to the trends in alkyl halide bond strengths. We examined this orbital overlap explanation using quantum mechanical calculations. Calculations reveal that orbital overlap increases rather than decreases with successively larger group 17 halogen atomic orbitals. This suggests that an orbital overlap explanation is physically incorrect and unneeded. Alternative to orbital overlap, we briefly discuss physically correct models for rationalizing halogen bond strength and acidity based on quantum mechanical valence bond theory and molecular orbital theory.

Despite the prevalence of the N-H aziridine motif in bioactive natural products and the clear advantages of this unprotected parent structure over N-protected derivatives as a synthetic building block, no practical methods have emerged for direct synthesis of this compound class from unfunctionalized olefins. Here, we present a mild, versatile method for the direct stereospecific conversion of structurally diverse mono-, di-, tri-, and tetrasubstituted olefins to N-H aziridines using O-(2,4-dinitrophenyl)hydroxylamine (DPH) via homogeneous rhodium catalysis with no external oxidants. This method is operationally simple (i.e., one-pot), scalable, and fast at ambient temperature, furnishing N-H aziridines in good-to-excellent yields. Likewise, N-alkyl aziridines are prepared from N-alkylated DPH derivatives. Quantum-mechanical calculations suggest a plausible Rh-nitrene pathway.

, 61 (2014); 343 Science et al. Jawahar L. Jat Aziridines from Olefins Direct Stereospecific Synthesis of Unprotected N-H and N-Me This copy is for your personal, non-commercial use only. clicking here. colleagues, clients, or customers by , you can order high-quality copies for your If you wish to distribute this article to others here. following the guidelines can be obtained by Permission to republish or repurpose articles or portions of articles ): January 3, 2014 www.sciencemag.org (this information is current as of The following resources related to this article are available online at http://www.sciencemag.org/content/343/6166/61.full.html version of this article at: including high-resolution figures, can be found in the online Updated information and services, http://www.sciencemag.org/content/suppl/2013/12/31/343.6166.61.DC1.html can be found at: Supporting Online Material http://www.sciencemag.org/content/343/6166/61.full.html#related found at: can be related to this article A list of selected additional articles on the Science Web sites http://www.sciencemag.org/content/343/6166/61.full.html#related-urls 1 articles hosted by HighWire Press; see: cited by This article has been