Andrew L. Cooksy

A Labile and Catalytically Active Imidazol‐2‐yl Fragment System

N-heterocyclic carbenes (NHCs) and their complexes are excellent catalysts for a broad array of organic transformations, where the NHC ligands impart useful electronic and steric properties to metal centers. In these systems, with commonly used ancilliary NHC ligands that are substituted at nitrogen atom(s) by alkyl, aryl, or other groups, all catalytic transformations take place at the metal center, which is stabilized and/or activated by the NHC ligand. However, transformations that may possibly involve both the metal center and at one ring nitrogen of the NHC ligand are much less common, 5c,e–g] and are limited to protic NHC complexes or their conjugated bases. Thus, the N H function of a protic NHC complex (A or D ; Scheme 1) could

Finding the Proton in a Key Intermediate of anti-Markovnikov Alkyne Hydration by a Bifunctional Catalyst

The secondary structure of a bifunctional catalyst positions a crucial reactive proton in the final intermediate of anti-Markovnikov alkyne hydration to give an aldehyde. NMR coupling and isotopic labeling studies elucidate the location of this proton and its involvement in hydrogen bonding.

Role of diacetyl metabolite in alcohol toxicity and addiction via electron transfer and oxidative stress

There are many gaps in our knowledge of the molecular basis of alcohol toxicity and addiction. Metabolism affords mainly acetic acid via acetaldehyde. A minor metabolite, diacetyl (an α-dicarbonyl), arises from the aldehyde. We propose that this C4 entity and/or its iminium derivatives from condensation with protein amino groups plays important roles in bioresponses. A review of the literature reveals substantial support for this premise. Reduction potentials for diacetyl and its iminium derivatives fall in the range favorable for catalytic electron transfer in vivo, which can generate oxidative stress via reactive oxygen species due to redox cycling. Oxidative stress and reactive oxygen species are linked to toxicity associated with major organs by alcohol. The α-dicarbonyl moiety in related substances is believed to induce various toxic responses, such as Alzheimer’s disease, mutagenesis, and carcinogenesis. In addition to discussion of addiction and computational studies, potential applications for health improvement are suggested.

Multimodal Study of Secondary Interactions in Cp*Ir Complexes of Imidazolylphosphines Bearing an NH Group

Hydrogen bonding phenomena are explored using a combination of X-ray diffraction, NMR and IR spectroscopy, and DFT calculations. Three imidazolylphosphines R(2)PImH (ImH = imidazol-2-yl, R = t-butyl, i-propyl, phenyl, 1a-1c) and control phosphine (i-Pr)(2)PhP (1d) lacking an imidazole were used to make a series of complexes of the form Cp*Ir(L(1))(L(2))(phosphine). In addition, in order to suppress intermolecular interactions with either imidazole nitrogen, 1e, a di(isopropyl)imidazolyl analogue of 1b was made along with its doubly (15)N-labeled isotopomer to explore bonding interactions at each imidazole nitrogen. A modest enhancement of transfer hydrogenation rate was seen when an imidazolylphosphine ligand 1b was used. Dichloro complexes (L(1) = L(2) = Cl, 2a-2c,2e) showed intramolecular hydrogen bonding as revealed by four X-ray structures and various NMR and IR data. Significantly, hydride chloride complexes [L(1) = H, L(2) = Cl, 3a-3c and 3e-((15)N)(2)] showed stronger hydrogen bonding to chloride than hydride, though the solid-state structure of 3b evinced intramolecular Ir-H...H-N bonding reinforced by intermolecular N...H-N bonding between unhindered imidazoles. These results are compared to literature examples, which show variations in preferred hydrogen bonding to hydride, halide, CO, and NO ligands. Surprising differences were seen between the dichloro complex 2b with isopropyl groups on phosphorus, which appeared to exist as a mixture of two conformers, and related complex 2a with tert-butyl groups on phosphorus, which exists in chlorinated solvents as a mixture of conformer 2a-endo and chelate 5a-Cl, the product of ionization of one chloride ligand. This difference became apparent only through a series of experiments, especially (15)N chemical shift data from 2D (1)H-(15)N correlation. The results highlight the difficulty of characterizing hemilabile, bifunctional complexes and the importance of innocent ligand substituents in determining structure and dynamics.

The fine-structure intervals of (N-14)+ by far-infrared laser magnetic resonance

The far-infrared laser magnetic resonance spectra associated with both fine-structure transitions in 14N+ in its ground 3P state have been recorded. This is the first laboratory observation of the J = 1 t 0 transition and its frequency has been determined two orders of magnitude more accurately than previously. The remeasurement of the J = 2 t 1 spectrum revealed a small error in the previous laboratory measurements. The finestructure splittings (free of hyperfine interactions) determined in this work are AElo = 1461.13190 (61) GHz

Electron Transfer as a Potential Cause of Diacetyl Toxicity in Popcorn Lung Disease

Diacetyl, a butter-flavoring component, has recently attracted scientific and media attention because it has been implicated as an agent that induces popcorn lung disease in exposed plant workers. This disease, officially referred to as bronchiolitis obliterans, entails exposure-induced compromise to the lungs epithelial barrier function. In this review, we present a novel molecular mechanism (electron transfer, ET) designed to explain how diacetyl and its imine derivatives might interact to produce lung damage. We relate the fact that diacetyl and related compounds possess reduction potentials amenable to electron transfer (ET) in vivo. The electrochemical nature of these toxicants can potentially disrupt normal ET processes, generate reactive oxygen species (ROS), and participate in cell signaling events. Condensation of diacetyl with protein may also play a role in the toxicity caused by this compound. ET is a common feature of toxic substances, usually involving their metabolites which can operate per se or through reactions that generate ROS and oxidative stress (OS). Examples of agents capable of ET are quinone and metal compounds, aromatic nitro compounds, and iminium salts. Among compounds that generate ET, the alpha-dicarbonyl ET class, of which diacetyl is a member, is much less studied. This review emphasizes diacetyl as an agent that acts through oxidative processes to cause its effects. However, we also treat related substances that appear to act by a similar mechanism. This mechanism forms a theoretical framework capable of describing the mechanism by which diacetyl may induce its effects and is in accord with various physiological activities displayed by other alpha-dicarbonyl substances. Examples of substances that may act by mechanisms similar to that displayed by diacetyl include cyclohexane-1,2-dione, marinopyrroles, reactive carbonyl species, the bacterial signaling agent DPD, and advanced glycation end products.

Encapsulation of a metal complex within a self-assembled nanocage: synergy effects, molecular structures, and density functional theory calculations.

A novel palladium-based metallacage was self-assembled. This nanocage displayed two complementary effects that operate in synergy for guest encapsulation. Indeed, a metal complex, [Pt(NO2)4](2-), was hosted inside the cavity, as demonstrated by solution NMR studies. Single-crystal X-ray diffraction shows that the guest adopts two different orientations, depending on the nature of the host-guest interactions involved. A density functional theory computational study is included to rationalize this type of host-guest interaction. These studies pave the way to a better comprehension of chemical interaction and transformation within confined nanospaces.

Rotational spectra of the carbon-chain radicals HC5O, HC6O, and HC7O

Three new free carbon-chain radicals, HC5O, HC6O, and HC7O, and their deuterated isotopic species have been observed by Fourier transform microwave spectroscopy of a supersonic molecular beam. In contrast to the shorter HCnO radicals, these all have linear heavy-atom backbones and 2Pi electronic ground states. Like the isovalent HCnS radicals, the ground states of the HCnO radicals alternate with odd and even numbers of carbon atoms: those of HC5O and HC7O are 2Pi1/2 and that of HC6O is 2Pi3/2. From frequency measurements between 6 and 26 GHz, the rotational constant B, the centrifugal distortion constant D, and the lambda-type doubling and magnetic hyperfine constants have been determined to high precision for each chain. Predicted properties from coupled-cluster calculations are also reported for chains up to HC9O. The production of HCnO radicals for n even was highly favored when O2 was used as the source of oxygen, but those with n odd were best produced with CO.

Accurate determination of the fine-structure intervals in the 3P ground states of C-13 and C-12 by far-infrared laser magnetic resonance

In this work we present accurate values for the fine-structure intervals in the 3P ground state of neutral atomic carbon-12 and carbon-I3 as obtained from laser magnetic resonance spectroscopy. The rigorous analysis of 13C hyperfine structure, the measurement of resonant fields for 13C transitions at several additional far-infrared laser frequencies, and the increased precision of the 12C measurements permit significant improve- ment in the evaluation of these energies relative to earlier work. The J = 2 c 1 interval is 809.3435(9) GHz in 12C and 809.3489(10) GHz in I3C, while we find values of 492.1611(12) GHz and 492.1628(20) GHz, respec- tively, for the J = 1 c 0 splittings. These results will expedite the direct and precise measurement of these transitions in interstellar sources and should assist in the determination of the interstellar 12C/l 3C abundance ratio. Subject headings: atomic processes - interstellar: abundances - line identifications

Novel, unifying mechanism for amphotericin B and other polyene drugs: electron affinity, radicals, electron transfer, autoxidation, toxicity, and antifungal action.

Amphotericin B is the most important member of the macrolide polyene antibiotics. There has been recent focus on mode of action involving membrane ion channels. The present report provides extensive evidence based on literature reports and computational studies on electron affinity for a multifaceted approach to therapeutic action and drug toxicity. Aspects involved include electron affinity, electron transfer, reactive oxygen species and oxidative stress in relation to mechanisms of drug action and toxicity. Other features addressed are autoxidation, metabolism, therapeutic properties (mainly antifungal), pro-oxidant action, antioxidant properties and analogy to conjugated dicarbonyls.