The Cholinergic Selectivity of FDA-Approved and Metabolite Compounds Examined with Molecular-Docking-Based Virtual Screening.

The search for selective anticholinergic agents stems from varying cholinesterase levels as Alzheimer's Disease progresses from the mid to late stage. In this computational study, we probed the selectivity of FDA-approved and metabolite compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with molecular-docking-based virtual screening. The results were evaluated using locally developed codes for the statistical methods. The docking-predicted selectivity for AChE and BChE was predominantly the consequence of differences in the volume of the active site and the narrower entrance to the bottom of the active site gorge of AChE.

Selective Depolymerization of Lignin Towards Isolated Phenolic Acids Under Mild Conditions.

The selective transformation of lignin to value-added biochemicals (e. g., phenolic acids) in high yields is incredibly challenging due to its structural complexity and many possible reaction pathways. Phenolic acids (PA) are key building blocks for various aromatic polymers, but the isolation of PAs from lignin is below 5 wt.% and requires harsh reaction conditions. Herein, we demonstrate an effective route to selectively convert lignin extracted from sweet sorghum and poplar into isolated PA in a high yield (up to 20 wt.% of lignin) using a low-cost graphene oxide-urea hydrogen peroxide (GO-UHP) catalyst under mild conditions (<120 °C). The lignin conversion yield is up to 95 %, and the remaining low molecular weight organic oils are ready for aviation fuel production to complete lignin utilization. Mechanistic studies demonstrate that pre-acetylation allows the selective depolymerization of lignin to aromatic aldehydes with a decent yield by GO through the Cα activation of ß-O-4 cleavage. A urea-hydrogen peroxide (UHP) oxidative process is followed to transform aldehydes in the depolymerized product to PAs by avoiding the undesired Dakin side reaction due to the electron-withdrawing effect of the acetyl group. This study opens a new way to selectively cleave lignin side chains to isolated biochemicals under mild conditions.

Polymer Nanocomposites for Photocatalytic Degradation and Photoinduced Utilizations of Azo-Dyes.

Specially designed polymer nanocomposites can photo-catalytically degrade azo dyes in wastewater and textile effluents, among which TiO2-based nanocomposites are outstanding and extensively explored. Other nanocomposites based on natural polymers (i.e., chitosan and kaolin) and the oxides of Al, Au, B, Bi, Fe, Li, and Zr are commonly used. These nanocomposites have better photocatalytic efficiency than pure TiO2 through two considerations: (i) reducing the hole/electron recombination rate by stabilizing the excited electron in the conducting band, which can be achieved in TiO2-nanocomposites with graphene, graphene oxide, hexagonal boron nitride (h-BN), metal nanoparticles, or doping; (ii) decreasing the band energy of semiconductors by forming nanocomposites between TiO2 and other oxides or conducting polymers. Increasing the absorbance efficiency by forming special nanocomposites also increases photocatalytic performance. The photo-induced isomerization is exploited in biological systems, such as artificial muscles, and in technical fields such as memory storage and liquid crystal display. Heteroaryl azo dyes show remarkable shifts in photo-induced isomerization, which can be applied in biological and technical fields in place of azo dyes. The self-assembly methods can be employed to synthesize azo-dye polymer nanocomposites via three types of interactions: electrostatic interactions, London forces or dipole/dipole interactions between azo dyes, and photo alignments.

Catalytic Urea Synthesis from Ammonium Carbamate Using a Copper(II) Complex: A Combined Experimental and Theoretical Study.

The synthesis of urea fertilizer is currently the largest CO2 conversion process by volume in the industry. In this process, ammonium carbamate is an intermediate en route to urea formation. We determined that the tetraammineaquacopper(II) sulfate complex, [Cu(NH3)4(OH2)]SO4, catalyzed the formation of urea from ammonium carbamate in an aqueous solution. A urea yield of up to 18 ± 6% was obtained at 120 °C after 15 h and in a high-pressure metal reactor. No significant urea formed without the catalyst. The urea product was characterized by Fourier transform infrared (FT-IR), powder X-ray diffraction (PXRD), and quantitative 1H{13C} NMR analyses. The [Cu(NH3)4(OH2)]SO4 catalyst was then recovered at the end of the reaction in a 29% recovery yield, as verified by FT-IR, PXRD, and quantitative UV-vis spectroscopy. A precipitation method using CO2 was developed to recover and reuse 66 ± 3% of Cu(II). The catalysis mechanism was investigated by the density functional theory at the B3LYP/6-31G** level with an SMD continuum solvent model. We determined that the [Cu(NH3)4]2+ complex is likely an effective catalyst structure. The study of the catalysis mechanism suggests that the coordinated carbamate with [Cu(NH3)4]2+ is likely the starting point of the catalyzed reaction, and carbamic acid can be involved as a transient intermediate that facilitates the removal of an OH group. Our work has paved the way for the rational design of catalysts for urea synthesis from the greenhouse gas CO2.

Incorporation of Cellulose Nanocrystals into Graphene Oxide Membranes for Efficient Antibiotic Removal at High Nutrient Recovery.

Two-dimensional (2D) material-based membranes hold great promise in wastewater treatment. However, it remains challenging to achieve highly efficient and precise small molecule/ion separation with pure 2D material-fabricated lamellar membranes. In this work, laminated graphene oxide (GO)-cellulose nanocrystal (CNC) hybrid membranes (GO/CNC) were fabricated by taking advantages of the unique structures and synergistic effects generated from these two materials. The characterization results in physiochemical properties, and the structure of the as-synthesized hybrid membranes displayed enhanced membrane surface hydrophilicity, enhanced crumpling surface structure, and slightly enlarged interlayer-spacing with the incorporation of CNCs. Water permeability increases by two to four times with the addition of different CNC weight ratios in comparison to a pristine GO membrane. The optimal GO/CNC membrane achieved efficient rejection toward three typical antibiotics at 74.8, 90.9, and 97.2% for sulfamethoxazole (SMX), levofloxacin (Levo), and norfloxacin (Nor), respectively, while allowing a high passage of desirable nutrients such as NO3- and H2PO4-. It was found that SMX removal is primarily governed by electrostatic repulsion, while adsorption plays a crucial role in removing Levo and Nor. Moreover, the density functional theory calculations confirmed the increased antibiotic removal in the presence of an organic foulant, humic acid. Such a 2D material-based hybrid membrane offers a new strategy to develop fit-for purpose membranes for resource recovery and water separation.

Depolymerization of Lignin into Monophenolics by Ferrous/Persulfate Reagent under Mild Conditions.

This study aimed to use a persulfate together with transition metal ions as the reagent to effectively depolymerize lignin into monophenolic compounds under mild conditions (ambient pressure, temperature <100 °C). The Box-Behnken experimental design in combination with the response surface methodology was applied to obtain optimized reaction conditions. The results showed that this reagent could depolymerize up to 99 % of lignin dimers to mainly veratraldehyde. This reaction also successfully depolymerized industrial lignins with a high yield of phenolic oils and monophenolic compounds. Quantum chemistry calculations using the density functional theory level indicated that the persulfate free radical attacks Cß to break the ß-O-4 bond of lignin through a five-membered ring mechanism. This mechanism using persulfate free radicals has a lower activation barrier than that using hydroxyl radicals. Gel permeation chromatography and 2D-NMR spectroscopy demonstrated the effective cleavage of the ß-O-4 bonds of lignin after depolymerization.

The Reactivity of Ambident Nucleophiles: Marcus Theory or Hard and Soft Acids and Bases Principle?

The model reactions CH3 X + (NH-CH=O)M ➔ CH3 -NH-NH═O or NH═CH-O-CH3 + MX (M = none, Li, Na, K, Ag, Cu; X = F, Cl, Br) are investigated to demonstrate the feasibility of Marcus theory and the hard and soft acids and bases (HSAB) principle in predicting the reactivity of ambident nucleophiles. The delocalization indices (DI) are defined in the framework of the quantum theory of atoms in molecules (QT-AIM), and are used as the scale of softness in the HSAB principle. To react with the ambident nucleophile NH═CH-O- , the carbocation H3 C+ from CH3 X (F, Cl, Br) is actually a borderline acid according to the DI values of the forming C…N and C…O bonds in the transition states (between 0.25 and 0.49), while the counter ions are divided into three groups according to the DI values of weak interactions involving M (M…X, M…N, and M…O): group I (M = none, and Me4 N) basically show zero DI values; group II species (M = Li, Na, and K) have noticeable DI values but the magnitudes are usually less than 0.15; and group III species (M = Ag and Cu(I)) have significant DI values (0.30-0.61). On a relative basis, H3 C+ is a soft acid with respect to group I and group II counter ions, and a hard acid with respect to group III counter ions. Therefore, N-regioselectivity is found in the presence of group I and group II counter ions (M = Me4 N, Li, Na, K), while O-regioselectivity is observed in the presence of the group III counter ions (M = Ag, and Cu(I)). The hardness of atoms, groups, and molecules is also calculated with new functions that depend on ionization potential (I) and electron affinity (A) and use the atomic charges obtained from localization indices (LI), so that the regioselectivity is explained by the atomic hardness of reactive nitrogen atoms in the transition states according to the maximum hardness principle (MHP). The exact Marcus equation is derived from the simple harmonic potential energy parabola, so that the concepts of activation free energy, intrinsic activation barrier, and reaction energy are completely connected. The required intrinsic activation barriers can be either estimated from ab initio calculations on reactant, transition state, and product of the model reactions, or calculated from identity reactions. The counter ions stabilize the reactant through bridging N- and O-site of reactant of identity reactions, so that the intrinsic barriers for the salts are higher than those for free ambident anions, which is explained by the increased reorganization parameter Δr. The proper application of Marcus theory should quantitatively consider all three terms of Marcus equation, and reliably represent the results with potential energy parabolas for reactants and all products. For the model reactions, both Marcus theory and HSAB principle/MHP principle predict the N-regioselectivity when M = none, Me4 N, Li, Na, K, and the O-regioselectivity when M = Ag and Cu(I). © 2019 Wiley Periodicals, Inc.

O-Regioselective Synthesis with the Silver Salt Method.

The excellent O-regioselectivity of the glycosidation of the ambident 2-O-substituted 5-fluorouracil (5-FU) via the silver salt method is computationally investigated at the MP2/6-311++G(2d,p):DZP//B3LYP/6-31+G(d):DZP level of theory. The reactions studied are those between 1-bromo-1-deoxy-2,3,4,6-tetra-O-acetyl-α-d-glucopyranose and the silver salts of 5-FU, 2-O-butyl-5-FU, and 2-O-benzyl-5-FU. Two pathways are considered as follows: (A) one where the silver and bromide ion do not interact, and (B) another where the silver and bromide ion interact in the transition states. Because the O-reaction barriers are much lower (by 13.3-22.2 kcal/mol) than N-reaction barriers in both pathways, the O-regioselectivity of the silver salt method can be satisfactorily explained by either path A or path B. Furthermore, path B, where Ag and Br interact consistently, has lower activation barriers than the corresponding path A (by 6.8-17.4 kcal/mol) in both N- and O-reactions. This computational result can be attributed to the following reasons: (1) the speeding-up effect in Koenigs-Knorr reactions due to the addition of silver carbonate into the reaction mixture; (2) the halogens being pulled away by silver ions from halides, as proposed by Kornblum and co-workers; and (3) the oxocarbenium ion involvement in the glycosidation reactions. The large energy difference between N- and O-transition states originates from the association between Ag and N-(O-) of the ambident unit (-N3-C4=O4) that shows significant covalent character so that the O-reaction transition states of the silver salt method benefit from favorable ionic interaction (C+···O-) and favorable covalent interaction (Ag···N). These two favorable interactions are in agreement with the hard and soft acids and bases principle; the former is a hard-hard interaction and the latter is a soft-soft interaction.

Theoretical Studies of the Glycosidation of 2-O-Substituted 5-Fluorouracil: N-Regioselective Synthesis with the Phase-Transfer-Catalysis Method.

The observed N-regioselective glycosidation of 2-O-substituted 5-fluorouracil (5-FU) via the phase-transfer-catalysis (PTC) method was investigated computationally. The Gibbs free energy reaction barrier of the N-reaction between the 5-FU anion and 1-bromo-1-deoxy-2,3,4,6-tetra-O-acetyl-α-d-glucopyranose was computed at the MP2/6-311++G(2d,p)//B3LYP/6-31+G* level. The calculated transition states were, in general, quite "loose", with the ambident reaction sites at the N3- or O4-positions on 5-FU located approximately 2.0 Å from the anomeric carbon. With the SN2 mechanism, the formation of ß-glycosides was explained by the characteristics of transition states, and the N-regioselectivity was explained by three considerations: (1) the conformations of initial complexes and the structural requirement of the reactions; (2) the formation of an ionic pair between nBu4N+ and 2-O-substituted 5-FU anions; and (3) the thermodynamic conversion of O-glycosides to N-glycosides. The reactions between the oxocarbenium ion and the 2-O-substituted 5-FU anions (the fast step of SN1 mechanism) were also examined at the same level of theory. Because there were no "promoters" to extract Br in the PTC method, the SN1 mechanism might have an unfavorably high barrier to produce oxocarbenium ion. However, both the formation of ß-glycosides and the experimentally observed N-regioselectivity could also be explained by the SN1 mechanism: The former was explained by the neighboring group participation, and the latter was explained by the formation of ionic pairs between nBu4N+ and 2-O-substituted 5-FU anions. The formation of ionic pairs possibly changed the diffusion-controlled mechanism into an activation-controlled mechanism. Two factors were demonstrated by Marcus theory to play an important role for the experimentally observed N-resioselectivity in the PTC method: (1) the thermodynamic stability of N-products over O-products; (2) the formation of ionic pair between nBu4N+ and 2-O-substituted 5-FU anions.

Towards the accurate and efficient calculation of optical rotatory dispersion using augmented minimal basis sets.

It has been recognized that quantum-chemical predictions of dispersive (nonresonant) chiroptical phenomena are exquisitely sensitive to the periphery of the electronic wavefunction. To further elaborate and potentially exploit this assertion, linear-response calculations of specific optical rotation were performed within the framework of density-functional theory (DFT) by augmenting small basis sets (e.g., STO - 3G and 3 - 21G) for the core and valence electrons with diffuse functions taken from substantially larger bases (e.g., aug-cc-pVXZ where X = D, T, or Q). Of particular interest was the ability of such computationally efficient (augmented small-basis) model chemistries to reproduce results derived from more expensive (canonical large-basis) schemes. The results appear to be quite promising, with the augmented minimal-basis ansatz often yielding wavelength-resolved rotatory powers close to those deduced from standard DFT(B3LYP)/aug-cc-pVXZ treatments. Analogous linear-response analyses were performed by means of coupled-cluster singles and doubles (CCSD) theory, once again leading to augmented small-basis estimates of specific rotation in reasonable accord with their large-basis counterparts. Although CCSD predictions were deemed to be slightly worse than those obtained from DFT, they still were of sufficient quality for such reduced-basis calculations to be considered viable for exploratory work.

Examination of DFT and TDDFT methods I.

We investigated DFT and TDDFT methods in the sense of the molecular orbital (MO) theory and in the framework of the quantum theory of atoms in molecules (QT-AIM). The detailed investigations for the ground state and the pi --> pi* excited state of ethene clarified three aspects about DFT and TDDFT methods: First, the DFT methods included electron correlation effects by directly changing MO energies and MO electron density distributions. Second, MO occupation numbers explained why the delocalization indices (DIs) obtained from DFT wave function files apparently differed from DIs obtained from the conventional correlated wave function files. At last, the significant underestimation of the excitation energy for the pi --> pi* adiabatic excited states of ethene by TDDFT methods can be attributed to the exact degeneracy of HOMO (pi) and LUMO (pi*), a special case of charge transfer (CT) excited states.

Examination of DFT and TDDFT methods II.

We investigated the isomerization energies for C(8) alkanes (n-octane and 2,2,3,3-tetra-methyl butane) and 1-X-propenes (X = CH(3), F, Cl, Br) and the excited states for tropolone. The recently implemented TDDFT gradients enabled us to optimize the adiabatic excited-state structures and to obtain wave function files for excited-state electron density analyses with 25 functionals. The dispersion interactions had been found to be important for predicting the isomerization energies for n-octane and 2,2,3,3-tetra-methyl butane and for cis- and trans-1-X-propenes (X = CH(3), F, Cl, Br). B3LYP failed to predict the isomerization energies for the first case but succeeded for the latter. We noticed that the integrated electron density and the merging contour values in the electron density difference plots were related to the isomerization energies; the DFT functionals (LSDA, BHandH, VSXC, and M052X) that could correctly account for the dispersion forces produced a greater electron density response for 2,2,3,3-tetramethyl butane than n-octane. Although the faster proton transfer reaction rate in the A(1)B(2) excited state relative to the X(1)A(1) ground state of tropolone could be reproduced only by M052X, the three newly designed functionals (BMK, CAM-B3LYP, and M052X) apparently performed better than other DFT functionals. The C-C' bond lengths of the C(s) symmetry excited state were possibly underestimated by DFT methods; the underestimation of C-C' bond lengths contributed to the high proton transfer barriers in the A(1)B(2) excited state of tropolone.

Disparate behavior of carbonyl and thiocarbonyl compounds: acyl chlorides vs thiocarbonyl chlorides and isocyanates vs isothiocyanates.

The reaction of benzoyl chloride with methanol catalyzed by pyridine is 9 times more rapid than is the same reaction with thiobenzoyl chloride. The difference in reactivity, as well as the dealkylation reactions that occur when the reaction of thiobenzoyl chloride is catalyzed by bases such as Et(3)N, can be understood in terms of the charge distributions in the intermediate acylammonium ions. The reaction of PhNCO with ethanol occurs at a much higher rate (4.8 x 10(4)) than that of PhNCS, corresponding to a difference in activation free energies for the additions of 6 kcal/mol. Transition states for each of these reactions were located, and each involves two alcohol molecules in a hydrogen bonded six-membered ring arrangement. Information concerning differences in reactivity was derived from analysis of Hirshfeld atomic charge distributions and calculated hydrogenolysis reaction energies.

Excited states and photochemistry of bicyclo[1.1.0]butane.

Calculations on the excited states of bicyclo[1.1.0]butane in the gas phase by different theoretical methods using several basis sets were performed. In general, the agreement between calculated and experimental excitation energies for bicyclo[1.1.0]butane in the gas phase is very good. Reviews of the solution-phase photochemistry of bicyclo[1.1.0]butane as well as previous calculations on the ground and excited states of bicyclo[1.1.0]butane are given to provide a necessary perspective of the photochemistry of bicyclo[1.1.0]butane in solution. To simulate the solution-phase photochemistry of bicyclo[1.1.0]butane, a well potential is added to the Kirkwood-Onsager model for obtaining solvation energies of molecules in solution. The addition of the well potential gives rise to a blue-shift of all gas-phase excitation energies in solution. However, there is also the very important added effect of providing an increase in Rydberg-valence mixing of solution-phase excited states. It is this mixing of antibonding valence character into the solution-phase excited states that is necessary to explain the solution-phase photochemistry of bicyclo[1.1.0]butane through bond-breaking and the formation of a conical intersection intermediate.

Intramolecular Nonbonded Attractive Interactions: 1-Substituted Propenes.

Whereas cis-substituted alkenes are normally significantly less stable than the trans-isomers, there is a group of 1-substituted propenes (X = F, OMe, Cl, Br, SMe) where the cis-isomers are the more stable. The calculated structures show that there is steric repulsion with the cis-isomers. However, this is overcome by attractive Coulombic interactions when X = F or OMe and by attractive dispersive interactions when X = Cl or Br. It was possible to calculate the magnitude of the latter term via the summation of the appropriate MP2 pair energies. The calculated and observed energy differences could be reproduced by a summation of steric, electrostatic, and dispersive interactions.

Optical rotatory dispersion of 2,3-hexadiene and 2,3-pentadiene.

The specific rotation of (P)-2,3-hexadiene (1) was measured as a function of wavelength for the gas phase, the neat liquid, and solutions. There was a surprisingly large difference between the gas phase and condensed phase values. The specific rotation was calculated using B3LYP and CCSD, and the difference in energy between the three low energy conformers was estimated at the G3 level. The Boltzmann-averaged CCSD-calculated rotations using the gauge independent velocity gauge representation, as well as the B3LYP values, are in agreement with the gas-phase experimental values. In order to avoid possible problems associated with the conformers of 1, 2,3-pentadiene (2) also was examined. Here again, there was a large difference between the gas-phase and condensed-phase specific rotations, with the CCSD velocity gauge (and B3LYP) results being close to the gas-phase experimental values. The possibility that 2,3-pentadiene could be distorted on going from the gas to liquid phase, thereby accounting for the effect of phase on the specific rotation, was examined via a Monte Carlo statistical mechanics simulation. No effect on the geometry was found. Specific rotations of 1 found in solutions were similar to those for the liquid phase, indicating that the phase difference was not due to association.

Effect of substituents and conformations on the optical rotations of cyclic oxides and related compounds. relationship between the anomeric effect and optical rotation.

The effect of substituents on the specific rotation of substituted cyclic oxides (X = F, Cl, CN, and HCC) and related compounds was studied via geometry optimization at the B3LYP/6-311+G** level followed by calculations of the specific rotation with B3LYP/aug-cc-pVDZ and, when practical, also with B3LYP/aug-cc-pVTZ. In some cases chiral samples were prepared so that the calculated specific rotations could be compared with experimental data. With most compounds there was only a minor effect of the basis set on the specific rotations. With the oxiranes and oxetanes, the chloro derivative gave a different behavior than the other substituents, but all substituents behaved in the same fashion with trans-2-methyl-1-X-cyclopropanes. Therefore the unusual behavior of chlorooxirane probably results from an interaction between oxygen and chlorine rather than being due to the presence of a three-membered ring. Chlorine is also an unusual substituent for the tetrahydrofurans. The effect of conformation on the calculated specific rotations was examined with the axial and equatorial 2-substituted tetrahydropyrans, where the anomeric effect is operative with the axial substituent, and also the 3-substituted tetrahydropyrans that would not be subject to the anomeric effect. The unusual effect of chlorine was seen only when it is antiperiplanar with respect to the oxygen.

Correlation effects in EOM-CCSD for the excited states: evaluated by AIM localization index (LI) and delocalization index (DI).

We have extended the evaluation and interpretation of QTAIM (quantum theory of atoms in molecules) localization and delocalization indices lambda (LI) and delta (DI) to electronic excited states by studying ground states (at HF and CCSD levels) and excited states (at CIS and EOM-CCSD) of H2C=CH2, HCCH, H2C=O, H2C=S, CO2, CS2, and SO2. These molecules undergo extensive geometrical changes upon the excitation to the valence adiabatic excited singlet state. The importance of Coulomb correlation effects was demonstrated by comparing the LIs and DIs at none-correlated levels (HF and CIS) and those at correlated levels (CCSD and EOM-CCSD). In interpreting the changes in the magnitudes of the LIs and DIs, we made use of simple molecular orbital and Walsh-diagram analyses. Coulomb correlation is important in determining the magnitude of the LIs and DIs and obtaining geometries that are close to experiment.

Sum-over-states calculation of the specific rotations of some substituted oxiranes, chloropropionitrile, ethane, and norbornenone.

A sum-over-states approach has been applied to the calculation of the specific rotations of several substituted oxiranes, 2-chloropropionitrile, and 30 degrees-rotated ethane. In each case, the first few excited states proved to have only a relatively small effect on the calculated specific rotation. It was necessary to use a very large number of excited states in order to achieve convergence with the results of the more direct linear response method. However, the latter does not give information on which excited states are important in determining the specific rotation. Norbornenone is unique in that its greatly enhanced specific rotation as compared to norbornanone is associated with the low-energy n-pi* transition. The C=C bond orbitals interact with the C=O in the LUMO, and a density difference plot for going from the ground state to the first excited state clearly shows the perturbation of the C=C.

Permanganate oxidation of alkenes. Substituent and solvent effects. Difficulties with MP2 calculations.

The permanganate oxidation of alkenes has been studied both experimentally and computationally. Transition state structures were located for the reaction of permanganate ion with a variety of monosubstituted alkenes at the B3LYP/6-311++G** level. Although the calculated activation energy for the reaction with ethene was reasonable, the calculated effect of substituents, based on the energies of the reactants, was much larger than that experimentally found. This was shown to be due to the formation of an intermediate charge-dipole complex which led to the transition state. Reaction field calculations found the complex to disappear in a high dielectric constant medium, and the range of activation energies for the reaction in solution became quite small. MP2 calculations were carried out in order to have a comparison with the DFT results. MP2-MP4 gave unusual results for calculations on permanganate ion as well as chromate ion and iron tetraoxide. They also gave markedly unreasonable results for the activation energy of the reaction of permanganate with ethane. CCSD/6-311++G** calculations gave satisfactory results for permanganate ion and chromate ion. At this level of theory, the reaction of permanganate with ethene was found to have a very early transition state, when the bond lengths of the reactants just began to change. The reaction was calculated to be very exothermic (-69 kcal/mol), and this was confirmed via calorimetry. The rates of permanganate oxidation of allyl alcohol and acrylonitrile were determined, and they had similar reactivities. The kinetics and the products of the reaction of permanganate with crotonate ion were examined in some detail.