Perfect Polar Alignment of Parallel Beloamphiphile Layers: Improved Structural Design Bias Realized in Ferroelectric Crystals of the Novel "Methoxyphenyl Series of Acetophenone Azines".

Invited for the cover of this issue are Harmeet Bhoday, Nathan Knotts, and Rainer Glaser at the Missouri University of Science and Technology. Joe Miner, the university mascot, is a silent and honorary co-author and personifies the spirit of the old west and the determination to succeed (our emphasis). The image depicts one (MeO-Ph, Y)-azine molecule and a model of a perfectly polar stacked bilayer. The floodlight illumination presents a graphic metaphor of second-harmonic generation (frequency doubling) by the crystalline ferroelectric materials. Read the full text of the article at 10.1002/chem.202400182.

Perfect Polar Alignment of Parallel Beloamphiphile Layers: Improved Structural Design Bias Realized in Ferroelectric Crystals of the Novel "Methoxyphenyl Series of Acetophenone Azines".

An improved design is described for ferroelectric crystals and implemented with the "methoxyphenyl series" of acetophenone azines, (MeO-Ph, Y)-azines with Y=F (1), Cl (2), Br (3), or I (4). The crystal structures of these azines exhibit polar stacking of parallel beloamphiphile monolayers (PBAMs). Azines 1, 3, and 4 form true racemates whereas chloroazine 2 crystallizes as a kryptoracemate. Azines 1-4 are helical because of the N-N bond conformation. In true racemates the molecules of opposite helicity (M and P) are enantiomers A(M) and A*(P) while in kryptoracemates they are diastereomers A(M) and B*(P). The stacking mode of PBAMs is influenced by halogen bonding, with 2-4 showcasing a kink due to directional interlayer halogen bonding, whereas fluoroazine 1 demonstrates ideal polar stacking by avoiding it. Notably, (MeO-Ph, Y)-azines display a stronger bias for dipole parallel alignment, attributed to the linearity of the biphenyl moiety as compared to the phenoxy series of (PhO, Y)-azines with their non-linear Ph-O-Ph moiety. The crystals of 1-4 all feature planar biphenyls and this synthon facilitates their crystallization through potent triple T-contacts and enhances their nonlinear optical (NLO) performance by increasing conjugation length and affecting favorable chromophore conformations in the solids.

Nuclear Magnetic Resonance Study of CO2 Capture by Fluoroalkylamines: Ammonium Ion pKa Depression via Fluorine Modification and Thermochemistry of Carbamylation.

We are developing energy-efficient and reversible carbon capture and release (CCR) systems that mimic the Lys201 carbamylation reaction in the active site of ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO). The multiequilibria scenario ammonium ion Xa ⇌ amine Xb ⇌ carbamic acid Xc ⇌ carbamate Xd requires the presence of both free amine and CO2 for carbamylation and is affected by the pKa(Xa). Two fluorination strategies aimed at ammonium ion pKa depression and low pH carbamylation were analyzed with (2,2,2-trifluoroethyl)butylamine 2b and 2,2-difluoropropylamine 3b and compared to butylamine 1b. The determination of K1 and ΔG1 of the carbamylation reactions requires the solution of multiequilibria systems of equations based on initial conditions, 1H NMR measurements of carbamylation yields over a wide pH range, and knowledge of K2-K5 values. K2 and K3 describe carbonic acid acidity, and ammonium ion acidities K4 were measured experimentally. We calibrated carbamic acid acidities K5 based on the measured value K6 of aminocarbamic acid using isodesmic reactions. The proton exchange reactions were evaluated with ab initio computations at the APFD/6-311+G* level in combination with continuum solvation models and explicit solvation. The utilities of 1-3 will be discussed as they pertain to the development of fluorine-modified RuBisCO-mimetic reversible CCR systems.

NMR Study of CO2 Capture by Butylamine and Oligopeptide KDDE in Aqueous Solution: Capture Efficiency and Gibbs Free Energy of the Capture Reaction as a Function of pH.

We have been interested in the development of rubisco-based biomimetic systems for reversible CO2 capture from air. Our design of the chemical CO2 capture and release (CCR) system is informed by the understanding of the binding of the activator CO2 (A CO2 ) in rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase). The active site consists of the tetrapeptide sequence Lys-Asp-Asp-Glu (or KDDE) and the Lys sidechain amine is responsible for the CO2 capture reaction. We are studying the structural chemistry and the thermodynamics of CO2 capture based on the tetrapeptide CH3 CO-KDDE-NH2 ("KDDE") in aqueous solution to develop rubisco mimetic CCR systems. Here, we report the results of 1 H NMR and 13 C NMR analyses of CO2 capture by butylamine and by KDDE. The carbamylation of butylamine was studied to develop the NMR method and with the protocol established, we were able to quantify the oligopeptide carbamylation at much lower concentration. We performed a pH profile in the multi equilibrium system and measured amine species and carbamic acid/carbamate species by the integration of 1 H NMR signals as a function of pH in the range 8≤pH≤11. The determination of ΔG1 (R) for the reaction R-NH2 +CO2 ← → ${ \mathbin{{\stackrel{\textstyle\rightarrow} { {\smash{\leftarrow}\vphantom{_{\vbox to.5ex{\vss}}}} } }} }$ R-NH-COOH requires the solution of a multi-equilibrium equation system, which accounts for the dissociation constants K2 and K3 controlling carbonate and bicarbonate concentrations, the acid dissociation constant K4 of the conjugated acid of the amine, and the acid dissociation constant K5 of the alkylcarbamic acid. We show how the multi-equilibrium equation system can be solved with the measurements of the daughter/parent ratio X, the knowledge of the pH values, and the initial concentrations [HCO3 - ]0 and [R-NH2 ]0 . For the reaction energies of the carbamylations of butylamine and KDDE, our best values are ΔG1 (Bu)=-1.57 kcal/mol and ΔG1 (KDDE)=-1.17 kcal/mol. Both CO2 capture reactions are modestly exergonic and thereby ensure reversibility in an energy-efficient manner. These results validate the hypothesis that KDDE-type oligopeptides may serve as reversible CCR systems in aqueous solution and guide designs for their improvement.

Rotation-Inversion Isomerization of Tertiary Carbamates: Potential Energy Surface Analysis of Multi-Paths Isomerization Using Boltzmann Statistics.

The front cover artwork is provided by Prof. Rainer Glaser's group at the Missouri University of Science and Technology. The image shows one of four potential energy surfaces generated from our rotation-inversion study of tertiary carbamates and highlights two of the eight possible transition state pathways between two ensembles of E- and Z-minima. In the context of synthetic studies of fluorinated carbamates R1 O-CO-N(R2 )CH2 CF3 , we unexpectedly observed two sets of 13 C NMR quartets for the CF3  group and we needed to understand their origin. Read the full text of the Research Article at 10.1002/cphc.2022005442.

Rotation-Inversion Isomerization of Tertiary Carbamates: Potential Energy Surface Analysis of Multi-Paths Isomerization Using Boltzmann Statistics.

Potential energy surface (PES) analyses at the SMD[MP2/6-311++G(d,p)] level and higher-level energies up to MP4(fc,SDTQ) are reported for the fluorinated tertiary carbamate N-ethyl-N-(2,2,2-trifluoroethyl) methyl carbamate (VII) and its parent system N,N-dimethyl methyl carbamate (VI). Emphasis is placed on the analysis of the rotational barrier about the CN carbamate bond and its interplay with the hybridization of the N-lone pair (NLP). All rotational transition state (TS) structures were found by computation of 1D relaxed rotational profiles but only 2D PES scans revealed the rotation-inversion paths in a compelling fashion. We found four unique chiral minima of VII, one pair each of E- and Z-rotamers, and we determined the eight unique rotational TS structures associated with every possible E/Z-isomerization path. It is a significant finding that all TS structures feature N-pyramidalization whereas the minima essentially contain sp2 -hybridized nitrogen. We will show that the TS stabilities are affected by the synergetic interplay between NLP/CO2 repulsion minimization, NLP→σ* (CO) negative hyperconjugation, and two modes of intramolecular through-space electrostatic stabilization. We demonstrate how Boltzmann statistics must be applied to determine the predicted experimental rotational barrier based on the energetics of all eight rotamerization pathways. The computed barrier for VII is in complete agreement with the experimentally measured barrier of the very similar fluorinated carbamate N-Boc-N-(2,2,2-trifluoroethyl)-4-aminobutan-1-ol II. NMR properties of VII were calculated with a variety of density functional/basis set combinations and Boltzmann averaging over the E- and Z-rotamers at our best theoretical level results in good agreement with experimental chemical shifts δ(13 C) and J(13 C,19 F) coupling constants of II (within 6 %).

Single-retainer all-ceramic resin-bonded fixed dental prostheses: Long-term outcomes in the esthetic zone.

OBJECTIVES: To present an update on the concept of cantilevered single-retainer all-ceramic resin-bonded fixed dental prostheses (RBFDPs) first presented 25 years ago in the Journal of Esthetic Dentistry. OVERVIEW: The initially presented case of the concept was followed clinically over 26 years and is presented along with two additional clinical long-term cases using varying methods to obtain an esthetic and hygienic ovate pontic design. Veneered alumina and zirconia ceramic (3 mol% yttria-tetragonal zirconia polycrystalline ceramic; 3Y-TZP) was used and bonded with a phosphate monomer containing luting resin after 50 µm alumina particle air-abrasion at 0.25 MPa pressure. The restorations replacing incisors did not debond and soft tissues in the pontic area were maintained over 26 years. CONCLUSIONS: Cantilevered single-retainer all-ceramic RBFDPs today made from veneered 3Y-TZP zirconia ceramic can be considered a standard of care for the replacement of single incisors and provide an excellent esthetic outcome with a long-term preservation of soft tissues in the pontic area. CLINICAL SIGNIFICANCE: Bonding nonretentive oxides ceramics such as alumina and zirconia ceramic with phosphate monomer containing luting resins after alumina particle air-abrasion is durable over decades. This proves that bonding to zirconia ceramic is not of any problem when adequate methods are used. Single-retainer zirconia ceramic RBFDPs maintain soft tissues in the edentulous area of single missing incisors and often deem implants unessential for this indication.

Importance of Solvent-Bridged Structures of Fluorinated Diphenylalanines: Synthesis, Detailed NMR Analysis, and Rotational Profiles of Phe(2-F)-Phe(2-F), Phe(2-F)-Phe, and Phe-Phe(2-F).

The crystal structure of l-phenylalanyl l-phenylalanine (Phe-Phe, FF, a.k.a. diphenylalanine) is not merely noncentrosymmetric, but it is highly dipole parallel aligned. It is for this reason that FF is a nonlinear optical (NLO) material and exhibits strong second harmonic generation (SHG). Enhancement of the SHG response by ortho fluorination was demonstrated. Crystallization is nontrivial, and learning about the zwitterion structures in solution is important for the rational improvement of the crystallization process. Here, we present an NMR study of di-fluorinated FF (Phe(2-F)-Phe(2-F)) and mono-fluorinated FF isomers (Phe(2-F)-Phe and Phe-Phe(2-F)). The dipeptides were prepared by solid-phase synthesis and purified by high-performance liquid chromatography (HPLC). Their 1H and 13C NMR spectra were recorded in partially deuterated water (10% D2O), and two-dimensional (2D) NMR techniques were employed for signal assignments. The unambiguous assignments are reported of all chemical shifts for the aliphatic H and C atoms and of the C atoms of the carboxylate, the amide carbonyl, the CF carbons, and of every arene C atom in each phenyl ring. The dipeptides are trans amides and intramolecular hydrogen bonding between the ammonium group and the amide carbonyl restricts the H3N-CH-C(O) geometry. We explored the rotational profile of the diphenylalanines as a function of the τ = ∠(C-N-C-CO2) dihedral angle at the SMD(B3LYP/6-31G*) level without and with specific hydration and report the associated Karplus curves J(θ) vs θ = ∠(H-N-C-H). The rotational profiles show a maximum of three stationary structures, and relative conformer stabilities of the free diphenylalanines show that the conformation found in the crystal M1 is the least stable among the three, M3 > M2 ≫ M1. Specific water solvation makes all of the difference and adds a large competitive advantage to the water-bridged ion pair M1a. In fact, M1a becomes the most stable and dominant conformation for the parent diphenylalanine and mono1 F-FF and M1a becomes competitive with M3c for mono2 F-FF and di F-FF. Implications are discussed regarding the importance of the conformational preorganization of diphenylalanines in solution and the facility for their crystallization.

Origin of the Second-Order Proton Catalysis of Ferriin Reduction in Belousov-Zhabotinsky Reactions: Density Functional Studies of Ferroin and Ferriin Aggregates with Outer Sphere Ligands Sulfate, Bisulfate, and Sulfuric Acid.

The detailed mechanisms of Belousov-Zhabotinsky oscillating reactions continue to present grand challenges, even after half a century of study. The origin of the pH dependence of the oscillation pattern had never been rigorously identified. In our recent kinetic study of one of the key Belousov-Zhabotinsky reactions, the iron-catalyzed bromate oxidation of malonic acid, compelling agreement between experiments and kinetic simulations was achieved only with the inclusion of second-order proton catalysis of the reduction of the [Fe(phen)3]3+ species. After exhausting all other avenues in search of an explanation of this proton catalysis, we considered the possibility that the parent iron-phenanthroline complexes could aggregate with neutral and anionic outer sphere ligands (OSLs) in the highly concentrated sulfuric acid solution, and we hypothesized that OSL protonation would increase the capacity of the aggregated complex to oxidize the organic fuel. We performed potential energy surface analyses at the SMD(APFD/6-311G*) level of complexes of the types [Fe(phen)3(SO42-)m(HSO4-)n(H2SO4)o](c-2m-n)+ for ferriin (c = 3) and ferroin (c = 2) aggregated with m sulfate, n bisulfate, and o sulfuric acid OSLs. We present structures of the OSL aggregates, develop a nomenclature for their description, and characterize their electronic structure. The structural chemistry provides the foundation to discuss the ferroin/ferriin redox couple with emphasis on the relationship between the vertical electron affinities of ferriin aggregates and their OSL protonation states. For proton catalysis to manifest itself, double-protonation paths that are slightly endergonic should be present, and proton affinities of aggregated OSLs allow the identification of such double-protonation chains. As a first test of our mechanistic proposal for the second-order proton catalysis of the Belousov-Zhabotinsky reaction, the results presented here provide compelling evidence in support of the importance of outer sphere ligation of the iron catalyst.

Perfect Polar Alignment of Parallel Beloamphiphile Monolayers: Synthesis, Characterization, and Crystal Architectures of Unsymmetrical Phenoxy-Substituted Acetophenone Azines.

It remains a great challenge to achieve polar order in organic molecular crystals because anti-parallel alignment of side-by-side molecules is intrinsically preferred. We have addressed this problem with a rational design that focuses on the polar stacking of parallel beloamphiphile monolayers (PBAMs) with strong lateral quadrupole-quadrupole attractions. We employ arene-arene interactions as lateral synthons. The first successes were achieved with unsymmetrical donor (X), acceptor (Y) substituted acetophenone azines which form polar PBAMs with double T-contacts between the azines. Near-perfect alignment was achieved with the methoxy series of (MeO, Y)-azines with Y=Cl, Br, I. Here, we report on the synthesis, the characterization (GC/MS, 1 H NMR, 13 C NMR, FTIR), the crystallization, and the single-crystal X-ray analyses of the phenoxy series of (PhO, Y)-acetophenone azines with Y=F, Cl, Br, I. Properties of (RO, Y) azines were computed at the APFD/6-311G* level and are discussed with reference to p-nitroaniline (PNA). This (PhO, Y) series embodies an improved PBAM design based on triple T-contacts which is shown to facilitate faster crystallization and to produce larger crystals. Perfect polar-alignment has been achieved for the phenoxy series of (PhO, Y)-azines with Y=Cl, Br, I and the (PhO, F)-azine also features near-perfect dipole alignment.

Computational Investigation of the Thermochemistry of the CO2 Capture Reaction by Ethylamine, Propylamine, and Butylamine in Aqueous Solution Considering the Full Conformational Space via Boltzmann Statistics.

Rubisco is the enzyme responsible for CO2 fixation in nature, and it is activated by CO2 addition to the amine group of its lysine 201 side chain. We are designing rubisco-based biomimetic systems for reversible CO2 capture from ambient air. The oligopeptide biomimetic capture systems are employed in aqueous solution. To provide a solid foundation for the experimental solution-phase studies of the CO2 capture reaction, we report here the results of computational studies of the thermodynamics of CO2 capture by small alkylamines in aqueous solution. We studied CO2 addition to methyl-, ethyl-, propyl-, and butylamine with the consideration of the full conformational space for the amine and the corresponding carbamic acids and with the application of an accurate solvation model for the potential energy surface analyses. The reaction energies of the carbamylation reactions were determined based on just the most stable structures (MSS) and based on the ensemble energies computed with the Boltzmann distribution (BD), and it is found that ΔGBD ≈ ΔGMSS. The effect of the proper accounting for the molecular translational entropies in solution with the Wertz approach are much more significant, and the free energy of the capture reactions ΔWGBD is more negative by 2.9 kcal/mol. Further accounting for volume effects in solution results in our best estimates for the reaction energies of the carbamylation reactions of ΔWABD = -5.4 kcal/mol. The overall difference is ΔGBD - ΔWABD = 2.4 kcal/mol for butylamine carbamylation. The full conformational space analyses inform about the conformational isomerizations of carbamic acids, and we determined the relevant rotational profiles and their transition-state structures. Our detailed studies emphasize that, more generally, solution-phase reaction energies should be evaluated with the Helmholtz free energy and can be affected substantially by solution effects on translational entropies.

Video colorimetry of single-chromophore systems based on vector analysis in the 3D color space: Unexpected hysteresis loops in oscillating chemical reactions.

Colorimetry, the quantitative determination of color, usually of a digital image, has useful applications in diverse areas of research. Many methods have been proposed for translating the RGB data of an image to obtain concentration information. Among the many methods for RGB analysis, we focus on the vector projection method (VP), which is based on a vector analysis in 3D RGB color space. This method has the major advantages of being conceptually intelligible and generalizable to various systems. For solutions with variable concentrations of one chromophore, we will show that the analysis of the trace in RGB color space allows for a judgment about the reliability of the linear concentration dependence of the chromapostasi parameter. We discuss the theoretical underpinnings of the method in two test cases, a simple dye solution and a titration of an organic acid with phenolphthalein indicator. The VP method was then applied to the Ce-catalyzed Belousov-Zhabotinsky reaction with the expectation that the colorimetry would quantify [Ce4+] oscillations. Surprisingly, the 3D color space analysis revealed hysteresis loops and the origin and implications of this observation are discussed.

Aluminum alkoxy-catalyzed biomass conversion of glucose to 5-hydroxymethylfurfural: Mechanistic study of the cooperative bifunctional catalysis.

Density functional theory calculations were performed to understand the detailed reaction mechanism of aluminum alkoxy-catalyzed conversion of glucose to 5-hydroxymethylfurfural (HMF) using Al(OMe)3 as catalyst. Potential energy surfaces were studied for aggregates formed between the organic compounds and Al(OMe)3 and effects of the medium were considered via continuum solvent models. The reaction takes place via two stages: isomerization from glucose to fructose (stage I) and transformation of fructose to HMF (stage II). Stage II includes three successive dehydrations, which begins with a 1,2-elimination to form an enolate (i.e., B), continues with the formation of the acrolein moiety (i.e., D), and ends with the formation of the furan ring (i.e., HMF). All of these steps are facilitated by aluminum alkoxy catalysis. The highest barriers for stage I and stage II are 23.9 and 31.2 kcal/mol, respectively, and the overall catalytic reaction is highly exothermic. The energetic and geometric results indicate that the catalyzed reaction path has feasible kinetics and thermodynamics and is consistent with the experimental process under high temperature (i.e., 120 °C). Remarkably, the released water molecules in stage II act as the product, reactant, proton shuttle, as well as stabilizer in the conversion of fructose to HMF. The metal-ligand functionality of the Al(OMe)3 catalyst, which combines cooperative Lewis acid and Lewis base properties and thereby enables proton shuttling, plays a crucial role in the overall catalysis and is responsible for the high reactivity. © 2019 Wiley Periodicals, Inc.

Measurements and Simulations of the Acidity Dependence of the Kinetics of the Iron-Catalyzed Belousov-Zhabotinsky Reaction: Proton-Catalysis in the Electron Transfer Reaction Involving the [Fe(phen)3]3+ Species.

The acidity dependence of the iron-catalyzed bromate-malonic acid Belousov-Zhabotinsky reaction was studied in the range 0.36 M < [H2SO4]0 < 1.20 M, and the temporal evolutions of the oscillation patterns were analyzed. The experimental results show that the period times PT i decrease exponentially with increasing acidity and that the period times parallel the decrease of the reduction times RT with increasing acidity. Simulations using the reactions of the commonly accepted core reaction mechanism failed to match the measurements even in a qualitative fashion. However, we found that compelling agreement between the experiments and the simulations can be achieved over the entire range with the inclusion of second-order proton-catalysis of the oxidation of bromomalonic acid (BrMA) by the [Fe(phen)3]3+ species in the reaction identified in this paper as reaction 9 (R9), and this [H+] dependence is informative about the species involved in the outer sphere electron transfer reaction. The trication [Fe(phen)3]3+ species is stabilized by ion pairing and solvation, and one may anticipate the presence of [Fe(phen)3(HSO4) n(H2O) m](3- n)+ species ( n = 0-3). Our results suggest that the removal of aggregating HSO4- ions by protonation creates a better oxidant and facilitates the approach of the reductant BrMA, and the second-order [H+] dependence further suggests that BrMA is primarily oxidized by a doubly charged [Fe(phen)3(HSO4)1(L) k]2+ species. Considering the complexity of the BZ system and the uncertainties in the many reaction rate constants, we were somewhat surprised to find this high level of agreement by (just) the replacement of R9 by R9'. In fact, the near-quantitative agreement presents a powerful corroboration of the core reaction mechanism of the BrMA-rich BZ reaction, and the replacement of R9 by R9' extends the validity of this core reaction mechanism to acidities above and below the typical acidity of BZ reactions ([H+] ≈ 1 M).

Near-silence of isothiocyanate carbon in (13)C NMR spectra: a case study of allyl isothiocyanate.

(1)H and (13)C NMR spectra of allyl isothiocyanate (AITC) were measured, and the exchange dynamics were studied to explain the near-silence of the ITC carbon in (13)C NMR spectra. The dihedral angles α = ∠(C1-C2-C3-N4) and ß = ∠(C2-C3-N4-C5) describe the conformational dynamics (conformation change), and the bond angles γ = ∠(C3-N4-C5) and ε = ∠(N4-C5-S6) dominate the molecular dynamics (conformer flexibility). The conformation space of AITC contains three minima, Cs-M1 and enantiomers M2 and M2'; the exchange between conformers is very fast, and conformational effects on (13)C chemical shifts are small (νM1 - νM2 < 3 ppm). Isotropic chemical shifts, ICS(γ), were determined for sp, sp(x), and sp(2) N-hybridization, and the γ dependencies of δ(N4) and δ(C5) are very large (10-33 ppm). Atom-centered density matrix propagation trajectories show that every conformer can access a large region of the potential energy surface AITC(γ,ε,...) with 120° < γ < 180° and 155° < ε < 180°. Because the extreme broadening of the (13)C NMR signal of the ITC carbon is caused by the structural flexibility of every conformer of AITC, the analysis provides a general explanation for the near-silence of the ITC carbon in (13)C NMR spectra of organic isothiocyanates.

Isotopic labeling experiments that elucidate the mechanism of DNA strand cleavage by the hypoxia-selective antitumor agent 1,2,4-benzotriazine 1,4-di-N-oxide.

The 1,2,4-benzotriazine 1,4-dioxides are an important class of potential anticancer drugs that selectively kill the low-oxygen (hypoxic) cells found in solid tumors. These compounds undergo intracellular one-electron enzymatic reduction to yield an oxygen-sensitive drug radical intermediate that partitions forward, under hypoxic conditions, to generate a highly reactive secondary radical that causes cell killing DNA damage. Here, we characterized bioreductively activated, hypoxia-selective DNA-strand cleavage by 1,2,4-benzotriazine 1,4-dioxide. We found that one-electron enzymatic activation of 1,2,4-benzotriazine 1,4-dioxide under hypoxic conditions in the presence of the deuterium atom donor methanol-d4 produced nondeuterated mono-N-oxide metabolites. This and the results of other isotopic labeling studies provided evidence against the generation of atom-abstracting drug radical intermediates and are consistent with a DNA-damage mechanism involving the release of hydroxyl radical from enzymatically activated 1,2,4-benzotriazine 1,4-dioxides.

Electronic structures and spin density distributions of BrO2 and (HO)2BrO radicals. Mechanisms for avoidance of hypervalency and for spin delocalization and spin polarization.

The results are reported of an ab initio study of bromine dioxide BrO2, 1, and of the T-shaped trans- and cis-dihydroxides 2 and 3 of dihydrogen bromate (HO)2BrO. The thermochemistry has been explored of potential synthetic routes to (HO)2BrO involving water addition to BrO2, hydroxyl addition to bromous acid HOBrO, 4, protonation/reduction of bromic acid HOBrO2, 5, via tautomers 6-8 of protonated bromic acid, and by reduction/protonation of bromic acid via radical anion [HOBrO2](-), 9. The potential energy surface analyses were performed at the MP2(full)/6-311G* level (or better) and with the consideration of aqueous solvation at the SMD(MP2(full)/6-311G*) level (or better), and higher-level energies were computed at levels up to QCISD(full,T)/6-311++G(2df,2pd)//MP2. The addition of RO radical to bromous acid or bromite esters and the reduction of protonated bromic acid or protonated bromate esters are promising leads for possible synthetic exploration. Spin density distributions and molecular electrostatic potentials were computed at the QCISD(full)/6-311G*//MP2(full)/6-311G* level to characterize the electronic structures of 1-3. Both radicals employ maximally occupied (pseudo) π-systems to transfer electron density from bromine to the periphery. While the formation of the (3c-5e) π-system suffices to avoid hypervalency in 1, the formation of the (4c-7e) π-system in 2 or 3 still leaves the bromine formally hypervalent and (HO)2BrO requires delocalization of bromine density into σ*-SMOs over the trans O-Br-O moiety. Molecular orbital theory is employed to describe the mechanisms for the avoidance of hypervalency and for spin delocalization and spin polarization. The (4c-7e) π-system in 2 is truly remarkable in that it contains five π-symmetric spin molecular orbitals (SMO) with unique shapes.

Mechanistic models for LAH reductions of acetonitrile and malononitrile. Aggregation effects of Li+ and AlH3 on imide-enamide equilibria.

The results are reported of an ab initio study of the addition of LiAlH(4) to acetonitrile and malononitrile at the MP2(full)/6-311+G* level considering the effects of electron correlation at higher levels up to QCISD(T)/6-311++G(2df,2pd) and including ether solvation. All imide (RCH(2)CH═N(-)) and enamide (RCH(-)CH═NH ↔ RCH═CHN(-)H) adducts feature strong interactions between the organic anion and both Li(+) and AlH(3). The relative stabilities of the tautomeric LAH adducts are compared to the tautomer preference energies of the LiH adducts and of the hydride adducts of the nitriles. Alane affinities were determined for the lithium ion pairs formed by LiH addition to the nitriles. The results show that alane binding greatly affects the imide-enamide equilibria and that alane complexation might even provide a thermodynamic preference for the imide intermediate. While lithium enamides of malononitrile are much more stable than lithium imides, alane binding dramatically reduces the enamide preference so that both tautomers are present at equilibrium. Implications are discussed regarding to the propensity for multiple hydride reductions and with regard to the mechanism of reductive nitrile dimerization. A detailed mechanism is proposed for the formation of 2-aminonicotinonitrile (2ANN) in the LAH reduction of malononitrile.

Disproportionation of bromous acid HOBrO by direct O-transfer and via anhydrides O(BrO)2 and BrO-BrO2. An ab initio study of the mechanism of a key step of the Belousov-Zhabotinsky oscillating reaction.

The results are reported of an ab initio study of the thermochemistry and of the kinetics of the HOBrO disproportionation reaction 2HOBrO (2) ⇄ HOBr (1) + HBrO(3) (3), reaction ( R4' ), in gas phase (MP2(full)/6-311G*) and aqueous solution (SMD(MP2(full)/6-311G*)). The reaction energy of bromous acid disproportionation is discussed in the context of the coupled reaction system R2-R4 of the FKN mechanism of the Belousov-Zhabotinsky reaction and considering the acidities of HBr and HOBrO(2). The structures were determined of ten dimeric aggregates 4 of bromous acid, (HOBrO)(2), of eight mixed aggregates 5 formed between the products of disproportionation, (HOBr)(HOBrO(2)), and of four transition states structures 6 for disproportionation by direct O-transfer. It was found that the condensation of two HOBrO molecules provides facile access to bromous acid anhydride 7, O(BrO)(2). A discussion of the potential energy surface of Br(2)O(3) shows that O(BrO)(2) is prone to isomerization to the mixed anhydride 8, BrO-BrO(2), and to dissociation to 9, BrO, and 10, BrO(2), and their radical pair 11. Hence, three possible paths from O(BrO)(2) to the products of disproportionation, HOBr and HOBrO(2), are discussed: (1) hydrolysis of O(BrO)(2) along a path that differs from its formation, (2) isomerization of O(BrO)(2) to BrO-BrO(2) followed by hydrolysis, and (3) O(BrO)(2) dissociation to BrO and BrO(2) and their reactions with water. The results of the potential energy surface analysis show that the rate-limiting step in the disproportionation of HOBrO consists of the formation of the hydrate 12a of bromous acid anhydride 7 via transition state structure 14a. The computed activation free enthalpy ΔG(act)(SMD) = 13.6 kcal/mol for the process 2·2a → [14a](‡) → 12a corresponds to the reaction rate constant k(4) = 667.5 M(-1) s(-1) and is in very good agreement with experimental measurements. The potential energy surface analysis further shows that anhydride 7 is kinetically and thermodynamically unstable with regard to hydrolysis to HOBr and HOBrO(2) via transition state structure 14b. The transition state structure 14b is much more stable than 14a, and, hence, the formation of the "symmetrical anhydride" from bromous acid becomes an irreversible reaction for all practical purposes because 7 will instead be hydrolyzed as a "mixed anhydride" to afford HOBr and HOBrO(2). The mixed anhydride 8, BrO-BrO(2), does not play a significant role in bromous acid disproportionation.

On the reaction mechanism of tirapazamine reduction chemistry: unimolecular N-OH homolysis, stepwise dehydration, or triazene ring-opening.

The initial steps of the activation of tirapazamine (TPZ, 1, 3-amino-1,2,4-benzotriazine 1,4-N,N-dioxide) under hypoxic conditions consist of the one-electron reduction of 1 to radical anion 2 and the protonation of 2 at O(N4) or O(N1) to form neutral radicals 3 and 4, respectively. There are some questions, however, as to whether radicals 3 and/or 4 will then undergo N-OH homolyses 3 → 5 + ·OH and 4 → 6 + ·OH or, alternatively, whether 3 and/or 4 may react by dehydration and form aminyl radicals via 3 → 11 + H(2)O and 4 → 12 + H(2)O or phenyl radicals via 3 → 17 + H(2)O. These outcomes might depend on the chemistry after the homolysis of 3 and/or 4, that is, dehydration may be the result of a two-step sequence that involves N-OH homolysis and formation of ·OH aggregates of 5 and 6 followed by H-abstraction within the ·OH aggregates to form hydrates of aminyls 11 and 12 or of phenyl 17. We studied these processes with configuration interaction theory, perturbation theory, and density functional theory. All stationary structures of OH aggregates of 5 and 6, of H(2)O aggregates of 11, 12, and 17, and of the transition state structures for H-abstraction were located and characterized by vibrational analysis and with methods of electron and spin-density analysis. The doublet radical 17 is a normal spin-polarized radical, whereas the doublet radicals 11 and 12 feature quartet instabilities. The computed reaction energies and activation barriers allow for dehydration in principle, but the productivity of all of these channels should be low for kinetic and dynamic reasons. With a view to plausible scenarios for the generation of latent aryl radical species without dehydration, we scanned the potential energy surfaces of 2-4 as a function of the (O)N1-Y (Y = C5a, N2) and (O)N4-Z (Z = C4a, C3) bond lengths. The elongation of any one of these bonds by 0.5 Å requires less than 25 kcal/mol, and this finding strongly suggests the possibility of bimolecular reactions of the spin-trap molecules with 2-4 concomitant with triazene ring-opening.