Ensemble-averaged QM/MM kinetic isotope effects for the S(N)2 reaction of cyanide anions with chloroethane in DMSO solution

The existence of solvent fluctuations leads to populations of reactant-state (RS) and transition-state (TS) configurations and implies that property calculations must include appropriate averaging over distributions of values for individual configurations. Average kinetic isotope effects 〈KIE〉 for NC(-) + EtCl → NCEt + Cl(-) in DMSO solution at 30?°C are best obtained as the ratio 〈f(RS)〉/〈f(TS)〉 of isotopic partition function ratios separately averaged over all RS and TS configurations. In this way the hybrid AM1/OPLS-AA potential yields 〈KIE〉 values for all six isotopic substitutions (2° α-(2)H(2), 2° β-(2)H(3), α-(11)C/(14)C, leaving group (37)Cl, and nucleophile (13)C and (15)N) for this reaction in the correct direction as measured experimentally. These thermally-averaged calculated KIEs may be compared meaningfully with experiment, and only one of them differs in magnitude from the experimental value by more than one standard deviation from the mean. This success contrasts with previous KIE calculations based upon traditional methods without averaging. The isotopic partition function ratios are best evaluated using all (internal) vibrational and (external) librational frequencies obtained from Hessians determined for subsets of atoms, relaxed to local minima or saddle points, within frozen solvent environments of structures sampled along molecular dynamics trajectories for RS and TS. The current method may perfectly well be implemented with other QM or QM/MM methods, and thus provides a useful tool for investigating KIEs in relation to studies of chemical reaction mechanisms in solution or catalyzed by enzymes.     

Theoretical Study on the Gas‐Phase SN2 Reaction of Microhydrated Fluoride with Methyl Fluoride

The rate constants for the gas‐phase S_N2 reaction of F^?(H₂O) with CH₃F have been calculated using the dual‐level variational transition state theory including multidimensional tunneling from 50 to 500 K. Tunneling was found to dominate the reaction below 200 K. The deuterium, ¹³C, and ¹⁴C kinetic isotope effects (KIEs) and solvent (D₂O) isotope effects (SKIEs) were also calculated in the same temperature range. The results indicated that the deuterium and heavy water substitutions resulted in inverse KIEs (0.6～0.8 ) while the ¹³C and ¹⁴C substitutions resulted in normal KIEs (1.0～1.2) at room temperature. The calculated carbon KIEs increased significantly below 80 K due to the differences in the magnitude of the tunneling effects for different isotopic substitutions.     

Substrate‐Dependent H/D Kinetic Isotope Effects and the Role of the Di(μ‐oxo)diiron(IV) Core in Soluble Methane Monooxygenase: A Theoretical Study

Soluble methane monooxygenase (sMMO) is an enzyme that converts alkanes to alcohols using a di(μ‐oxo)diiron(IV) intermediate Q at the active site. Very large kinetic isotope effects (KIEs) indicative of significant tunneling are observed for the hydrogen transfer (H‐transfer) of CH₄ and CH₃CN; however, a relatively small KIE is observed for CH₃NO₂. The detailed mechanism of the enzymatic H‐transfer responsible for the diverse range of KIEs is not yet fully understood. In this study, variational transition‐state theory including the multidimensional tunneling approximation is used to calculate rate constants to predict KIEs based on the quantum‐mechanically generated intrinsic reaction coordinates of the H‐transfer by the di(μ‐oxo)diiron(IV) complex. The results of our study reveal that the role of the di(μ‐oxo)diiron(IV) core and the H‐transfer mechanism are dependent on the substrate. For CH₄, substrate binding induces an electron transfer from the oxygen to one Fe^IV center, which in turn makes the μ‐O ligand more electrophilic and assists the H‐transfer by abstracting an electron from the C?H σ orbital. For CH₃CN, the reduction of Fe^IV to Fe^III occurs gradually with substrate binding and H‐transfer. The charge density and electrophilicity of the μ‐O ligand hardly change upon substrate binding; however, for CH₃NO₂, there seems to be no electron movement from μ‐O to Fe^IV during the H‐transfer. Thus, the μ‐O ligand appears to abstract a proton without an electron from the C?H σ orbital. The calculated KIEs for CH₄, CH₃CN, and CH₃NO₂ are 24.4, 49.0, and 8.27, respectively, at 293 K, in remarkably good agreement with the experimental values. This study reveals that diverse KIE values originate mainly from tunneling to the same di(μ‐oxo)diiron(IV) core for all substrates, and demonstrate that the reaction dynamics are essential for reproducing experimental results and understanding the role of the diiron core for methane oxidation in sMMO.     

Effects on the Reactivity by Changing the Electrophilic Center from CO to CS: Contrasting Reactivity of Hydroxide,p‐Chlorophenoxide,and Butan‐2,3‐dione Monoximate in DMSO/H2O Mixtures

Second‐order rate constants have been measured spectrophotometrically for the reactions of O‐p‐nitrophenyl thionobenzoate ( 1 , PNPTB) with HO^?, butan‐2,3‐dione monoximate (Ox^?, α‐nucleophile), and p‐chlorophenoxide (p‐ClPhO^?, normal nucleophile) in DMSO/H₂O of varying mixtures at (25.0±0.1) °C. Reactivity of these nucleophiles significantly increases with increasing DMSO content. HO^? is less reactive than p‐ClPhO^? toward 1 up to 70 mol % DMSO although HO^? is over six pK_a units more basic in these media. Ox^? is more reactive than p‐ClPhO^? in all media studied, indicating that the α‐effect is in effect. The magnitude of the α‐effect (i.e., k/k_p) increases with the DMSO content up to 50 mol % DMSO and decreases beyond that point. However, the dependency of the α‐effect profile on the solvent for reactions of 1 contrasts to that reported previously for the corresponding reactions of p‐nitrophenyl benzoate ( 2 , PNPB); reactions of 1 result in much smaller α‐effects than those of 2 . Breakdown of the α‐effect into ground‐state (GS) and transition‐state (TS) effects shows that the GS effect is not responsible for the α‐effect across the solvent mixtures. The role of the solvent has been discussed on the basis of the bell‐shaped α‐effect profiles found in the current study as well as in our previous studies, that is, a GS effect in the H₂O‐rich region through H‐bonding interactions and a TS effect in the DMSO‐rich media through mutual polarizability interactions.     

Kinetic and ESR studies on the radical polymerization of α‐n‐(α′‐methylbenzyl) β‐ethyl itaconamates derived from racemic and (s)‐α‐methylbenzylamines

The polymerization of α‐N‐(α′‐methylbenzyl) β‐ethyl itaconamate derived from racemic α‐methylbenzylamine (RS‐MBEI) by initiation with dimethyl 2,2′‐azobisisobutyrate (MAIB) was studied in methanol kinetically and with ESR spectroscopy. The overall activation energy of polymerization was calculated to be 47 kJ/mol, a very low value. The polymerization rate (R_p ) at 60 °C was expressed by R_p = k[MAIB]^0.5±0.05[RS‐MBEI]^2.9±0.1. The rate constants of propagation (k_p ) and termination (k_t ) were determined by ESR. k_p was very low, ranging from 0.3 to 0.8 L/mol s, and increased with the monomer concentration, whereas k_t (4–17 × l0⁴ L/mol s) decreased with the monomer concentration. Such behaviors of k_p and k_t were responsible for the high dependence of R_p on the monomer concentration. R_p depended considerably on the solvent used. S‐MBEI, derived from (S)‐α‐methylbenzylamine, showed somewhat lower homopolymerizability than RS‐MBEI. The k_p value of RS‐MBEI at 60 °C in benzene was 1.5 times that of S‐MBEI. This was explicable in terms of the different molecular associations of RS‐MBEI and S‐MBEI, as analyzed by ¹H NMR. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4137–4146, 2000     

Understanding the Mechanisms of Unusually Fast HH,CH,and CC Bond Reductive Eliminations from Gold(III) Complexes

Carbon–carbon bond reductive elimination from gold(III) complexes are known to be very slow and require high temperatures. Recently, Toste and co‐workers have demonstrated extremely rapid C?C reductive elimination from cis‐[AuPPh₃(4‐F‐C₆H₄)₂Cl] even at low temperatures. We have performed DFT calculations to understand the mechanistic pathway for these novel reductive elimination reactions. Direct dynamics calculations inclusive of quantum mechanical tunneling showed significant contribution of heavy‐atom tunneling (>25 %) at the experimental reaction temperatures. In the absence of any competing side reactions, such as phosphine exchange/dissociation, the complex cis‐[Au(PPh₃)₂(4‐F‐C₆H₄)₂]⁺ was shown to undergo ultrafast reductive elimination. Calculations also revealed very facile, concerted mechanisms for H?H, C?H, and C?C bond reductive elimination from a range of neutral and cationic gold(III) centers, except for the coupling of sp³ carbon atoms. Metal–carbon bond strengths in the transition states that originate from attractive orbital interactions control the feasibility of a concerted reductive elimination mechanism. Calculations for the formation of methane from complex cis‐[AuPPh₃(H)CH₃]⁺ predict that at ?52 °C, about 82 % of the reaction occurs by hydrogen‐atom tunneling. Tunneling leads to subtle effects on the reaction rates, such as large primary kinetic isotope effects (KIE) and a strong violation of the rule of the geometric mean of the primary and secondary KIEs.     

Large Isotope Effects in Organometallic Chemistry

The kinetic isotope effect (KIE) is key to understanding reaction mechanisms in many areas of chemistry and chemical biology, including organometallic chemistry. This ratio of rate constants, k_H/k_D, typically falls between 1–7. However, KIEs up to 105 have been reported, and can even be so large that reactivity with deuterium is unobserved. We collect here examples of large KIEs across organometallic chemistry, in catalytic and stoichiometric reactions, along with their mechanistic interpretations. Large KIEs occur in proton transfer reactions such as protonation of organometallic complexes and clusters, protonolysis of metal–carbon bonds, and dihydrogen reactivity. C−H activation reactions with large KIEs occur with late and early transition metals, photogenerated intermediates, and abstraction by metal-oxo complexes. We categorize the mechanistic interpretations of large KIEs into the following three types: (a) proton tunneling, (b) compound effects from multiple steps, and (c) semi-classical effects on a single step. This comprehensive collection of large KIEs in organometallics provides context for future mechanistic interpretation.     

Kinetic isotope effects and rate constants for the gas‐phase reactions of three deuterated toluenes with OH from 298 to 353 K

The rate constants for the gas‐phase reactions of three deuterated toluenes with hydroxyl radicals were measured using the relative rate technique over the temperature range 298–353 K at about 1 atm total pressure. The OH radicals were generated by photolysis of H₂O₂, and helium was used as the diluent gas. The disappearance of reactants was followed by online mass spectrometry, which resulted in high time resolution, allowing for a large amount of data to be collected and used in the determination of the Arrhenius parameters. The following Arrhenius expressions have been determined for these reactions (in units of cm³ molecule^?1 s^?1): k=(6.42_?0.99^+1.17)×10^?13exp [(661±54)/T] for toluene‐d₃, k=(2.11_?0.69^+1.03)×10^?12exp [(287±128)/T]for toluene‐d₅, and k=(1.40^+0.44_?0.33)×10^?12exp [(404±88)/T]for toluene‐d₈. The kinetic isotope effects (KIEs, k_H/k_D) of these reactions were 1.003 ± 0.042 for all three compounds at 298 K. The KIE for toluene‐d₃ was temperature dependent; at 350 K, its KIE was 1.122^+0.048_?0.046. The KIE of toluene‐d₅ and toluene‐d₈ did not vary significantly with temperature. These KIE results suggest that methyl H‐atom abstraction is more important than aromatic OH addition at higher temperatures. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 821–827, 2012     

Unperturbed chain dimensions of isotactic polypropylene in theta solvents

The unperturbed mean-square end-to-end distance 〈R₀²〉 and its temperature variation d In 〈R₀²〉/dT for isotactic polypropylene have been estimated from intrinsic viscosity data in three theta solvents, i.e., diphenyl, diphenyl ether, and dibenzyl ether, measured at their θ temperatures as determined by precipitation temperature measurements. The characteristic ratios, 〈R₀²〉/nl², where n is the number of bonds of length l in the main chain, evaluated by assuming Φ = 2.87 × 10²¹, are 5.80 in diphenyl (at θ = 125.1°C.), 5.41 in diphenyl ether (at θ = 142.8°C.), and 4.56 in dibenzyl ether (at θ = 183.2°C.). These values lead to the temperature coefficient d In 〈R₀²〉/dT = ?4.09 × 10^?3 deg.^?1 Results are compared with the data previously reported on polyethylene.     

Chemical Ligation and Isotope Labeling to Locate Dynamic Effects during Catalysis by Dihydrofolate Reductase

Chemical ligation has been used to alter motions in specific regions of dihydrofolate reductase from E. coli and to investigate the effects of localized motional changes on enzyme catalysis. Two isotopic hybrids were prepared; one with the mobile N‐terminal segment containing heavy isotopes (²H, ¹³C, ¹⁵N) and the remainder of the protein with natural isotopic abundance, and the other one with only the C‐terminal segment isotopically labeled. Kinetic investigations indicated that isotopic substitution of the N‐terminal segment affected only a physical step of catalysis, whereas the enzyme chemistry was affected by protein motions from the C‐terminal segment. QM/MM studies support the idea that dynamic effects on catalysis mostly originate from the C‐terminal segment. The use of isotope hybrids provides insights into the microscopic mechanism of dynamic coupling, which is difficult to obtain with other studies, and helps define the dynamic networks of intramolecular interactions central to enzyme catalysis.     

Carbon-13 kinetic isotope effects in the decarbonylation of liquid formic acid of natural isotopic composition initiated by phosphorus pentoxide

The isotopic composition of the consecutive fractions of carbon monoxide produced in the decarbonylation of liquid formic acid of natural isotopic composition initiated by addition of phosphorus pentoxide has been measured in the temperature interval 19–100°C and the observed gradual decrease of the _PDB values and the increase of thek ₁₂/k ₁₃ ratio of the isotopic specific rate constants (KIE values) for each next fraction of CO have been interpreted in terms of conclusions presented in the first paper from this series¹ concerning the decarbonylation of HCOOH (F.A.) in concentrated and diluted with water phosphoric acid media. The initial fast dehydration of F.A. by phosphoric anhydride, P₂O₅, proceeds at room temperture with about 1% carbon-13 KIE. The (k ₁₂/k ₁₃) values increase with time, as the decarbonylation slows down due to the hydration of phosphorus pentoxide with water generated in dehydration of HCOOH and reach the plateau values characteristic for each reaction temperature. These increasing very slowly with reaction times at intermediate temperatures maximum values of (k ₁₂/k ₁₃) ratios are quite close to values of¹³C KIE observed in the decarbonylation of pure F.A. (k ₁₂/k ₁₃=1.0443 at 81°C). Addition of water to liquid F.A. at 90°C and at 100°C caused the further increase of the¹³C KIE. The detailed discussion of the¹³C KIE in the HCOOH–P₂O₅ system has been given.     

13C Kinetic Isotope Effect of the Pudovik Reaction

Abstract

¹³C kinetic isotope effect (KIE) was determined by means of ¹³C NMR for the carbonyl atom in 2-nitrobenzaldehyde in its reaction with 2H-2-oxo-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinane in acetonitrile at 25°C. The observed isotope effect k₁₂/k₁₃ = 1.0238 ± 0.0031 evidences that the formation of the P?C bond in the Pudovik reaction catalyzed by triethylamine is less advanced than the π-bond breakage of the aldehyde carbonyl group.     

Dynamic Monte Carlo Simulation on the Polymer Chain with One End Grafted on a Flat Surface

A linear polymer chain in good solvent condition with one end grafted on a infinitely large, impenetrable flat surface is investigated using dynamic Monte Carlo simulation on a simple cubic lattice. Chain shape and dimension, angular correlation between the direction of the end‐to‐end vector and that of the longest principal axis of inertia are studied and discussed. Results reveal that the asphericity of end‐grafted polymer chains is greater than that of free ones, the limit ratio 〈L₁²〉 : 〈L₂²〉 : 〈L₃²〉 is about 1 : 3.0 : 14.9. The limit of mean angle 〈θ〉 of end‐grafted chains is about 22°, smaller than that of free chains, indicating angular correlation between the direction of the end‐to‐end vector and that of the longest principal axis is reinforced.     

On the Importance of Decarbonylation as a Side‐Reaction in the Ruthenium‐Catalysed Dehydrogenation of Alcohols: A Combined Experimental and Density Functional Study

We report a density functional study (B97‐D2 level) of the mechanism(s) operating in the alcohol decarbonylation that occurs as an important side‐reaction during dehydrogenation catalysed by [RuH₂(H₂)(PPh₃)₃]. By using MeOH as the substrate, three distinct pathways have been fully characterised involving either neutral tris‐ or bis‐phosphines or anionic bis‐phosphine complexes after deprotonation. α‐Agostic formaldehyde and formyl complexes are key intermediates, and the computed rate‐limiting barriers are similar between the various decarbonylation and dehydrogenation paths. The key steps have also been studied for reactions involving EtOH and iPrOH as substrates, rationalising the known resistance of the latter towards decarbonylation. Kinetic isotope effects (KIEs) were predicted computationally for all pathways and studied experimentally for one specific decarbonylation path designed to start from [RuH(OCH₃)(PPh₃)₃]. From the good agreement between computed and experimental KIEs (observed k_H/k_D=4), the rate‐limiting step for methanol decarbonylation has been ascribed to the formation of the first agostic intermediate from a transient formaldehyde complex.     

Effect of polystyrene‐b‐poly(ethylene oxide) on self‐assembly of polystyrene‐b‐poly(N‐isopropylacrylamide) in aqueous solution

Mixed micelles of polystyrene‐b‐poly(N‐isopropylacrylamide) (PS‐b‐PNIPAM) and two polystyrene‐b‐poly(ethylene oxide) diblock copolymers (PS‐b‐PEO) with different chain lengths of polystyrene in aqueous solution were prepared by adding the tetrahydrofuran solutions dropwise into an excess of water. The formation and stabilization of the resultant mixed micelles were characterized by using a combination of static and dynamic light scattering. Increasing the initial concentration of PS‐b‐PEO in THF led to a decrease in the size and the weight average molar mass (〈M_w〉) of the mixed micelles when the initial concentration of PS‐b‐ PNIPAM was kept as 1 × 10^?3 g/mL. The PS‐b‐PEO with shorter PS block has a more pronounced effect on the change of the size and 〈M_w〉 than that with longer PS block. The number of PS‐b‐PNIPAM in each mixed micelle decreased with the addition of PS‐b‐PEO. The average hydrodynamic radius 〈R_h〉 and average radius of gyration 〈R_g〉 of pure PS‐b‐PNIPAM and mixed micelles gradually decreased with the increase in the temperature. Both the pure micelles and mixed micelles were stable in the temperature range of 18 °C–39 °C. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1168–1174, 2010     

Electrophilic Iron Catalyst Paired with a Lithium Cation Enables Selective Functionalization of Non‐Activated Aliphatic C−H Bonds via Metallocarbene Intermediates

Combining an electrophilic iron complex [Fe(^Fpda)(THF)]₂ ( 3 ) [^Fpda=N,N′‐bis(pentafluorophenyl)‐o‐phenylenediamide] with the pre‐activation of α‐alkyl‐substituted α‐diazoesters reagents by LiAl(OR^F)₄ [OR^F=(OC(CF₃)₃] provides unprecedented access to selective iron‐catalyzed intramolecular functionalization of strong alkyl C(sp³)?H bonds. Reactions occur at 25 °C via α‐alkyl‐metallocarbene intermediates, and with activity/selectivity levels similar to those of rhodium carboxylate catalysts. Mechanistic investigations reveal a crucial role of the lithium cation in the rate‐determining formation of the electrophilic iron‐carbene intermediate, which then proceeds by concerted insertion into the C?H bond.     

C(sp3)H Activation without a Directing Group: Regioselective Synthesis of N‐Ylide or N‐Heterocyclic Carbene Complexes Controlled by the Choice of Metal and Ligand

N‐Ylide complexes of Ir have been generated by C(sp³)?H activation of α‐pyridinium or α‐imidazolium esters in reactions with [Cp*IrCl₂]₂ and NaOAc. These reactions are rare examples of C(sp³)?H activation without a covalent directing group, which—even more unusually—occur α to a carbonyl group. For the reaction of the α‐imidazolium ester [ 3 H]Cl, the site selectivity of C?H activation could be controlled by the choice of metal and ligand: with [Cp*IrCl₂]₂ and NaOAc, C(sp³)?H activation gave the N‐ylide complex 4 ; in contrast, with Ag₂O followed by [Cp*IrCl₂]₂, C(sp²)?H activation gave the N‐heterocyclic carbene complex 5 . DFT calculations revealed that the N‐ylide complex 4 was the kinetic product of an ambiphilic C?H activation. Examination of the computed transition state for the reaction to give 4 indicated that unlike in related reactions, the acetate ligand appears to play the dominant role in C?H bond cleavage.     

Synthesis and properties of phosphorus containing polyester‐amides derived from 1,4‐bis(3‐aminobenzoyloxy)‐2‐(6‐oxido‐6H‐dibenz〈c,e〉〈1,2〉oxaphosphorin‐6‐yl) phenylene

A series of polyester‐amides that contain phosphorus were synthesized by low temperature solution condensation of 1,4‐bis(3‐aminobenzoyloxy)‐2‐(6‐oxido‐6H‐dibenz〈c,e〉〈1,2〉oxaphosphorin‐6‐yl) phenylene (III) with various aromatic acid chlorides in N‐methyl pyrrolidone (NMP). All polyester‐amides are amorphous and readily soluble in many organic solvents such as dimethylacetamide (DMAc), NMP, dimethylsulfoxide, and dimethylformamide at room temperature or on heating. Light yellow and flexible films of these polyester‐amides could be cast from the DMAc solutions. The polymers with an inherent viscosity of 0.26–0.72 dL/g were obtained in quantitative yields. These polyester‐amides have good mechanical properties (G′ of ∼ 10⁹ Pa up to 200°C) and good thermal and flame retardant properties. The glass transition temperatures of these polyester‐amides ranged from 250 to 273°C. The degradation temperatures (T_d 5%) in nitrogen ranged from 466 to 478°C and the char yields at 800°C were 59.6–65.2%. The limiting oxygen indexes of these polyester‐amides ranged from 35 to 43. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 891–899, 1999     

α‐Diamine Nickel Catalysts with Nonplanar Chelate Rings for Ethylene Polymerization

A series of novel α‐diamine nickel complexes, (ArNH‐C(Me)‐(Me)C‐NHAr)NiBr₂, 1 : Ar=2,6‐diisopropylphenyl, 2 : Ar=2,6‐dimethylphenyl, 3 : Ar=phenyl), have been synthesized and characterized. X‐ray crystallographic analysis showed that the coordination geometry of the α‐diamine nickel complexes is markedly different from conventional α‐diimine nickel complexes, and that the chelate ring (N‐C‐C‐N‐Ni) of the α‐diamine nickel complex is significantly distorted. The α‐diamine nickel catalysts also display different steric effects on ethylene polymerization in comparison to the α‐diimine nickel catalyst. Increasing the steric hindrance of the α‐diamine ligand by substitution of the o‐methyl groups with o‐isopropyl groups leads to decreased polymerization activity and molecular weight; however, catalyst thermal stability is significantly enhanced. Living polymerizations of ethylene can be successfully achieved using 1 /Et₂AlCl at 35 °C or 2 /Et₂AlCl at 0 °C. The bulky α‐diamine nickel catalyst 1 with isopropyl substituents can additionally be used to control the branching topology of the obtained polyethylene at the same level of branching density by tuning the reaction temperature and ethylene pressure.