Generation of oxynitrenes and confirmation of their triplet ground states

New sulfoximine- and phenanthrene-based photochemical precursors to oxynitrenes have been developed. These precursors have been used to examine the chemistry and spectroscopy of oxynitrenes. The first EPR spectra of oxynitrenes are reported and are consistent with their triplet ground states. Additional support for the triplet ground state of oxynitrenes is provided by trapping and reactivity studies, nanosecond time-resolved IR investigations, and computational studies.     

Thermal hydrogen-atom transfer from methane: the role of radicals and spin states in oxo-cluster chemistry

Hydrogen-atom transfer (HAT), as one of the fundamental reactions in chemistry, is investigated with state-of-the-art gas-phase experiments in conjunction with computational studies. The focus of this Minireview concerns the role that the intrinsic properties of gaseous oxo-clusters play to permit HAT reactivity from saturated hydrocarbons at ambient conditions. In addition, mechanistic implications are discussed which pertain to heterogeneous catalysis. From these combined experimental/computational studies, the crucial role of unpaired spin density at the abstracting atom becomes clear, in distinct contrast to recent conclusions derived from solution-phase experiments.     

Reactivity of biarylazacyclooctynones in copper-free click chemistry

The 1,3-dipolar cycloaddition of cyclooctynes with azides, also called "copper-free click chemistry", is a bioorthogonal reaction with widespread applications in biological discovery. The kinetics of this reaction are of paramount importance for studies of dynamic processes, particularly in living subjects. Here we performed a systematic analysis of the effects of strain and electronics on the reactivity of cyclooctynes with azides through both experimental measurements and computational studies using a density functional theory (DFT) distortion/interaction transition state model. In particular, we focused on biarylazacyclooctynone (BARAC) because it reacts with azides faster than any other reported cyclooctyne and its modular synthesis facilitated rapid access to analogues. We found that substituents on BARAC's aryl rings can alter the calculated transition state interaction energy of the cycloaddition through electronic effects or the calculated distortion energy through steric effects. Experimental data confirmed that electronic perturbation of BARAC's aryl rings has a modest effect on reaction rate, whereas steric hindrance in the transition state can significantly retard the reaction. Drawing on these results, we analyzed the relationship between alkyne bond angles, which we determined using X-ray crystallography, and reactivity, quantified by experimental second-order rate constants, for a range of cyclooctynes. Our results suggest a correlation between decreased alkyne bond angle and increased cyclooctyne reactivity. Finally, we obtained structural and computational data that revealed the relationship between the conformation of BARAC's central lactam and compound reactivity. Collectively, these results indicate that the distortion/interaction model combined with bond angle analysis will enable predictions of cyclooctyne reactivity and the rational design of new reagents for copper-free click chemistry.     

Cyclic Haloiodanes: Syntheses,Applications and Fundamental Studies

Hypervalent iodine reagents are powerful tools in contemporary organic synthesis. They have found numerous applications in modern oxidative transformations. The unique reactivity of hypervalent iodine allows access to unconventional electrophilic synthons. For example, electrophilic halogenation chemistry has been greatly expanded by the study of various haloiodanes. Cyclic λ³-haloiodanes are versatile reagents which can promote reactions such as halogenations, halocyclizations and oxidations. Their peculiar reactivity sets them apart from traditional sources of electrophilic halogens. Furthermore, they offer a broad range of reactivities which have been exploited in more diversified transformations. This review summarizes the different syntheses and derivatives of these cyclic haloiodanes, their applications and mechanistic insights as well as the relevant computational, structural and kinetic studies.     

Reactivity and Mechanistic Studies of the Reactions of Chlorodiphenylphosphine and Its Oxide with Methyl Glyoxylate,Glyoxylate Oximes,and Methyl Cyanoformate

In this work, we describe the reactivity of chlorodiphenylphosphine and its oxide, as well as diphenylphosphine, with some glyoxylate derivative systems: methyl glyoxylate, methyl or 8‐phenylneomenthyl glyoxylate oximes, and methyl cyanoformate. By analyzing the reactions outcomes and with the aid of computational chemistry, we propose some reaction mechanisms and molecular rearrangements.     

Modelling fundamental arene-borane contacts: spontaneous formation of a dibromoborenium cation driven by interaction between a borane Lewis acid and an arene π system

Reaction of 2,6-dimesityl pyridine (L(py)) with BBr(3) leads to the spontaneous formation of the trigonal dibromoborenium cation [L(py)·BBr(2)](+)via bromide ejection. Systematic structural and computational studies, and the reactivity displayed by a closely related N-heterocyclic carbene (NHC) donor, reveal the role played by arene-borane interactions in this chemistry. [L(py)·BBr(2)](+) features a structurally characterized (albeit weak) electrostatic interaction between the borane Lewis acid and flanking arene π systems.     

Application of the Systems Chemistry Approach on the Ammonolysis of 1-Ethoxycarbonyl- and 1-Phenoxycarbonyl-3-(2-thienyl)oxindoles. A Method to Predict Reactivity

The routine prediction of the reactivity of a complex, multifunctional molecule is a challenging and time-consuming procedure. In the last step of the synthesis of the well-known drug substance tenidap, a nonexpected difference was observed between the reactivities of two closely related carbamate moieties, the N-ethoxycarbonyl and the N-phenoxycarbonyl group. A detailed kinetic study, necessitating a significant computational effort, is described in the present paper for this reaction step. On the other hand, the systems chemistry concept, by analyzing the details of the electronic structure and the connections between functional groups in a fast and simple way, is also able to answer this question using various "-icity" parameters (aromaticity, carbonylicity, olefinicity). The complete systems chemistry approach involves all these conjugativicity parameters, while its further simplified version is based on only one key parameter, which is carbonylicity in the present case. The above methods were compared in terms of their predictive power. The results show that the systems chemistry concept, even its one-parameter version, is applicable for the characterization of this challenging reactivity issue.     

Computational study of ethylene,acetylene, and cyclopropene addition to heterocycles with two heteroatoms in the 1,2 position

The AM1 semiempirical and B3LYP density functional theory computational studies are undertaken with the target being to explore cycloaddition reactions with heterocycles that have two heteroatoms in the ring's 1 and 2 positions as an initial synthetic step in the preparation of allene's acetylene derivatives. Several qualitative computational approaches were used to evaluate the heterocycle reactivity, including two new approaches using electronic and bond order changes in transformation of the reactant pair into corresponding transition state structures. Finally, the reactivity was evaluated by computing activation barriers, and the feasibility of the proposed synthetic transformations was discussed.     

Integrating Molecular Modeling with Semiempirical Quantum Mechanical Calculations into the Upper-Level Inorganic Chemistry Course

The analysis of chemical bonding and reactivity from the perspective of molecular orbital theory is challenging for students at the undergraduate level. In an attempt to improve the instruction of this material in my upper-level inorganic chemistry course I developed a series of computational experiments using a molecular modeling program that can perform semiempirical quantum mechanical calculations. These exercises explore the chemistry of molecular systems through an analysis of the variation in the attractive and repulsive forces in the system as a function of structure or composition. The exercises challenge the analysis skills of the students by requiring them to consider how two or more factors contribute to the properties of the system. Examples of exercises that demonstrate different types of computational experiments are given. These sample exercises examine the structure of simple molecules, the reactivity of Lewis acids, and the bonding in transition metal complexes.     

Biological chemistry of organotin compounds: Interactions and dealkylation by dithiols

In this paper, we review our past and current efforts toward the elucidation of the biological chemistry of organotin compounds. In particular, we cover two prominent aspects of organotin compounds: their reactivity toward biological dithiols, and their degradation (or metabolization) mechanism using a combination of experimental and computational techniques.     

Special Collection: Computational Chemistry

Chemists know well the value of an experimental or a theoretical result, but what is the value of a computational result? Simulation is neither theory nor experience, nor a mere calculation tool, but a genuine way of approaching reality that is transforming the scientific method. In some cases, it offers explanations to observations or experiments that seem incomprehensible because they are too complex. In this case, the computation serves as a relief. An experiment that converges with a certain computation has more scientific value than an experiment that does not converge with anything at all. In other cases, contribution of computational chemistry is essential because there is no experimental manner to determine what happens during a chemical process; for instance, in the path from reactants to products in (fast) reactions. Now, computational chemistry provides additional information that is not possible to obtain from experiments, so it is a valuable complement to them. Indeed, fruitful synergy between computation and experiment has led to the approach of theory-driven experimentation. Finally, computational chemistry helps to legitimize models or theories that have little opportunity to be contrasted with reality. In this situation, computational chemistry is not experience, but it does substitute it in relation to theory. In the present special collection, we have examples of the different ways computational chemistry helps chemists to interpret the electronic and molecular structure of molecules and their reactivity.     

Molecular Magnets: The Synthesis and Characterization of High-Spin Nitrenes

Among all C-, N-, and O-centered polyradicals, high-spin nitrenes possess the largest magnetic anisotropy and are of considerable interest as multi-level molecular spin systems for exploration of organic molecular magnetism and quantum information processing. Although the first representatives of quintet and septet nitrenes were obtained almost 50 years ago, the experimental and theoretical studies of these highly reactive species became possible only recently, owing to new achievements in molecular spectroscopy and computational chemistry. Meanwhile, dozens of various quintet dinitrenes and septet trinitrenes were successfully characterized by IR, UV/Vis, and EPR spectroscopy, thus providing important information about the electronic structure, magnetic properties and reactivity of these compounds.     

Guidelines for publication of research results from force-field calculations

For the publication of research results, the chemical sciences community has had a long history of requiring authors to provide sufficient data so that their research results and procedures can be (1) understood, (2) critically evaluated, and (3) replicated by other competent scientists. The emergence of computational chemistry as a distinct area of research presents new challenges in defining criteria to meet these obligations. While much of the long-standing paradigm for experimental chemistry can be directly transferred to computational chemistry, some differences are apparent. A computational study does not give a product for which one can measure physical properties, nor are percent yields and recoveries available to demonstrate experimental success. Nonetheless, it is imperative that computational results be able to withstand the same scientific scrutiny as experimental ones. Like all fields of scientific endeavor, computational chemistry is also a dynamic science. The continuous and dramatic improvements in computational algorithms and increases in computing power over the last decade have made possible the study of chemical problems for which solutions by computational means previously were unattainable. Moreover, advances in computer technology have also changed the way these computational studies are carried out. For any new study, the traditional search for the nearest energy minimum may no longer be adequate, fewer assumptions and approximations may be acceptable, and even the nature of the data to be stored and reported may have evolved. For example, many computer algorithms have become sufficiently fast and convenient that it is more efficient to repeat some part of the overall calculation than to save and record the corresponding data that it generates. This document has been developed to provide guidance to chemists who employ computations of molecular structure, properties, reactivity, and dynamics as either a part or as the main thrust of a research report. It is derived in part from earlier work carried out by the Provisional Section Committee on Medicinal Chemistry of IUPAC (Gund, P.; Barry, D. C.; Blaney, J. M.; Cohen, C. N. J. Med. Chem., 1988, 31 , 2230–2234). ©1998 IUPAC     

The Computational Road to Better Catalysts

Computational studies, especially those that use density functional theory (DFT), have become pervasive in the characterization, mechanistic study, and optimization of homogeneous organometallic catalysts, and the “rational” design of such catalysts seems within reach once more. But how advanced, user‐friendly, and reliable are the computational tools that are currently available? Here we summarize the current state of the art for predictive computational organometallic chemistry in reference to the different stages of catalyst development by considering characterization, mechanistic studies, fine‐tuning/optimization, and evaluation of novel designs. We also assess critically where the strengths and weaknesses of computational studies lie and hence map out the road ahead for the design and discovery of novel catalysts in silico and in combination with targeted experimental studies.     

The AQUA-MER databases and aqueous speciation server: A web resource for multiscale modeling of mercury speciation

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.     

Functionalization of Alkynes by a (Salen)ruthenium(VI) Nitrido Complex

Exploring new reactivity of metal nitrides is of great interest because it can give insights to N₂ fixation chemistry and provide new methods for nitrogenation of organic substrates. In this work, reaction of a (salen)ruthenium(VI) nitrido complex with various alkynes results in the formation of novel (salen)ruthenium(III) imine complexes. Kinetic and computational studies suggest that the reactions go through an initial ruthenium(IV) aziro intermediate, followed by addition of nucleophiles to give the (salen)ruthenium(III) imine complexes. These unprecedented reactions provide a new pathway for nitrogenation of alkynes based on a metal nitride.     

Organic Chemistry as a Language and the Implications of Chemical Linguistics for Structural and Retrosynthetic Analyses

Methods of computational linguistics are used to demonstrate that a natural language such as English and organic chemistry have the same structure in terms of the frequency of, respectively, text fragments and molecular fragments. This quantitative correspondence suggests that it is possible to extend the methods of computational corpus linguistics to the analysis of organic molecules. It is shown that within organic molecules bonds that have highest information content are the ones that 1) define repeat/symmetry subunits and 2) in asymmetric molecules, define the loci of potential retrosynthetic disconnections. Linguistics‐based analysis appears well‐suited to the analysis of complex structural and reactivity patterns within organic molecules.     

Computational assessment of synthetic procedures

Synthetic chemistry is hard because some reasonable looking molecules cannot be made, because there are errors in the chemical literature, because it is easy to miss reaction possibilities and because even the shape of molecules is very difficult to determine. We propose an approach to the computational analysis of reactions that tries to circumvent these difficulties, by restricting the analysis to simple rules for reactivity that can generate a large number of competing pathways. This huge ensemble is filtered using computational methods to pick out the most likely pathways, and to suggest possible products.     

Aryloxide-based multidentate ligands for early transition metals and f-element metals

This article presents an overview of the chemistry of early transition metal and f-element complexes stabilized by aryloxide-based multidentate ligands. Preparations and reactivity studies of these compounds are discussed. The presence of the bridging units in this ligand system imposes a strong geometry constraint to the aryloxide groups, which leads the way to novel patterns of structure and reactivity.