Substituent effects on the reactions of aromatic triflones with para‐X‐anilines in methanol: Low intrinsic reactivity and transition state imbalances

A kinetic study is reported for S_NA_r reactions of 2,4,6‐tris(trifluoromethanesulfonyl) anisole 1a with a series of para‐X‐substituted anilines 2a–e in a methanol solution at various temperatures. The substituent effects on free energy (Δ^≠G), enthalpy (Δ^≠H), and entropy (Δ^≠S) of activation are examined. Aniline addition to triflone 1a is characterized by a β_X=0.57, α_Z=0.31, and an imbalance of I = α_Z–β_X=?0.26. The imbalance shows that resonance development lags behind C? N bond formation at the transition state. Interestingly, analysis of the results in terms of Marcus theory reveals that these S_NAr are associated with some extremely low intrinsic reactivity (log k_o=?1.25& © 2011 Wiley Peiodicals, Inc. Int J Chem Kinet 43: 255–262, 2011     

The enthalpy and entropy of activation for ethyl acetate saponification

The saponification of ethyl acetate was measured by conductimetry at different temperatures within a batch reactor. A new mathematical model for obtaining concentration profiles from conductivity was presented and used for reaction‐kinetics' determination. The Arrhenius parameters (A, E_a) showed good agreement with the previously published values. Basic transition‐state theory was used for obtaining the Gibbs energy (ΔG?), the enthalpy (ΔH?), and the entropy (ΔS?) of activation. The low enthalpy of activation and negative entropy of activation were consistent with a reaction pathway when forming a transition‐state complex. The suggested mechanism involves OH^?, acting as a general base for removing proton from one of the hydroxide hydrating water, placed directly between it and the ester. The nucleophile from the water then attacks at the electrophilic C of the ester, breaking the π bond, and creating a tetrahedral intermediate. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 692–698, 2012 This article was published online on 24 January 2012. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected on 16 July 2012.     

Molecular Shape and Crystal Packing: a Study of C12H12 Isomers,Real and Imaginary

Isomeric C₁₂H₁₂ hydrocarbon molecules with widely different constitution and shape are analysed for their packing ability. Some correspond to known compounds with known crystal structures, but some are invented hypothetical molecules designed to have low packing efficiency. For each isomer, a large number of close‐packed, low‐energy crystal structures was generated by computer, with lattice energies within a range of a few kJ mol⁻¹. Molecules with linear chains, triple bonds and Me groups tend to have larger molecular volume, lower lattice energy and lower crystal density than cyclic or cage isomers. The calculated crystal structures for each isomer show an inverse relationship between packing energy and cell volume. Although the slope dE/dV varies from molecule to molecule, the product of slope and free space stays roughly constant; less efficient crystal packings thus appear to be less sensitive to an increase in cell volume. Lattice‐vibrational frequencies and the corresponding contributions to thermal vibrational entropy were estimated for real and virtual crystal structures. For a given isomer, as expected, a higher entropy goes with a larger cell volume, but different isomers show different entropy/volume relationships. At 300 K, TΔS differences among computational polymorphs may compete with ΔH differences, thus making the lattice‐vibrational entropy estimation a relevant factor in crystal‐structure prediction.     

Effect of the repeated unit length of guest polymers on the molecular motion of polymer blends within a miscible window

The effect of the repeated unit length on the substantially increasing molecular motion and entropy change (?TΔS_m) of polymer blends was investigated with solid‐state ¹³C NMR and differential scanning calorimetry within a miscible window. The hydrogen‐bonding strength, from the formation of the phenolic–polyester interaction, was not high enough to overcome the breaking‐off of the self‐association of the phenolic. With respect to the increasing repeated unit length, the polyester resonance intensity of the solid‐state ¹³C NMR spectra was weakened because of the reduction in the cross‐polarization efficiency in highly mobile samples. The glass‐transition temperature of the blend and the proton spin–lattice relaxation time from NMR experiments were also reduced. The effect of the reduced hydrogen‐bonding strength on blending brought about a tendency of higher entropy (?TΔS_m) and higher molecular mobility of the blend. Accordingly, poly(decamethylene adipate) possessed the longest repeated unit length and exhibited the most mobile one in this phenolic/polyester blend family. The molecular segmental motion and entropy progressively increased while the repeated unit length of the guest polymers increased within a miscible window. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 679–686, 2003     

NMR Spectroscopic Study of the Self‐Aggregation of 3‐Hexen‐1,5‐diyne Derivatives

The self‐assembly of polycatenar molecules derived from 1,6‐diphenyl‐3,4‐dipropyl‐3‐hexen‐1,5‐diyne has been studied in detail by solution NMR spectroscopy. The analysis of the concentration‐ and temperature‐dependent evolution of the chemical shifts and the diffusion coefficients in [D₁₂]cyclohexane agrees well with an isodesmic model of association in this solvent. The association constants for the stacking and entropy and enthalpy of the process have been obtained. The driving force for the aggregation process is provided by a negative enthalpy (ΔH), which is partially compensated by a negative entropy (ΔS). A structural study of the self‐assembly in solution has been carried out with the help of NOESY NMR spectroscopic experiments.     

Critical behavior of megabase-size DNA toward the transition into a compact state

We studied the changes in the higher-order structure of a megabase-size DNA (S120-1 DNA) under different spermidine (SPD) concentrations through single-molecule observations using fluorescence microscopy (FM) and atomic force microscopy (AFM). We examined the difference between the folding transitions in S120-1 DNA and sub-megabase-size DNA, T4 DNA (166 kbp). From FM observations, it is found that S120-1 DNA exhibits intra-chain segregation as the intermediate state of transition, in contrast to the all-or-none nature of the transition on T4 DNA. Large S120-1 DNA exhibits a folding transition at lower concentrations of SPD than T4 DNA. AFM observations showed that DNA segments become aligned in parallel on a two-dimensional surface as the SPD concentration increases and that highly intense parallel alignment is achieved just before the compaction. S120-1 DNA requires one-tenth the SPD concentration as that required by T4 DNA to achieve the same degree of parallel ordering. We theoretically discuss the cause of the parallel ordering near the transition into a fully compact state on a two-dimensional surface, and argue that such parallel ordering disappears in bulk solution.     

Elongation/compaction of giant DNA caused by depletion interaction with a flexible polymer

Structural changes in giant DNA induced by the addition of the flexible polymer Polyethylene Glycol (PEG) were examined by the method of single-DNA observation. In dilute DNA conditions, individual DNA assumes a compact state via a discrete coil-globule transition, whereas in concentrated solution, DNA molecules exhibit an extended conformation via macroscopic phase segregation. The long-axis length of the stretched state in DNA is about 10(3) times larger than that of the compact state. Phase segregation at high DNA concentrations occurs at lower PEG concentrations than the compaction at low DNA concentrations. These opposite changes in the conformation of DNA molecule are interpreted in terms of the free energy, including depletion interaction.     

Efficient Intramolecular Hydroalkoxylation of Unactivated Alkenols Mediated by Recyclable Lanthanide Triflate Ionic Liquids: Scope and Mechanism

Lanthanide triflate complexes of the type [Ln(OTf)₃] (Ln=La, Sm, Nd, Yb, Lu) serve as effective, recyclable catalysts for the rapid intramolecular hydroalkoxylation (HO)/cyclization of primary/secondary and aliphatic/aromatic hydroxyalkenes in imidazolium‐based room‐temperature ionic liquids (RTILs) to yield the corresponding furan, pyran, spirobicyclic furan, spirobicyclic furan/pyran, benzofuran, and isochroman derivatives. Products are straightforwardly isolated from the catalytic solution, conversions exhibit Markovnikov regioselectivity, and turnover frequencies are as high as 47 h^?1 at 120 °C. The ring‐size rate dependence of the primary alkenol cyclizations is 5>6, consistent with a sterically controlled transition state. The hydroalkoxylation/cyclization rates of terminal alkenols are slightly more rapid than those of internal alkenols, which suggests modest steric demands in the cyclic transition state. Cyclization rates of aryl‐functionalized hydroxyalkenes are more rapid than those of the linear alkenols, whereas five‐ and five/six‐membered spirobicyclic skeletons are also regioselectively closed. In cyclization of primary, sterically encumbered alkenols, turnover‐frequency dependence on metal‐ionic radius decreases by approximately 80‐fold on going from La³⁺ (1.160 Å) to Lu³⁺ (0.977 Å), presumably reflecting steric impediments along the reaction coordinate. The overall rate law for alkenol hydroalkoxylation/cyclization is v≈k[catalyst]¹[alkenol]¹. An observed ROH/ROD kinetic isotope effect of 2.48 (9) is suggestive of a catalytic pathway that involves kinetically significant intramolecular proton transfer. The present activation parameters—enthalpy (ΔH^≠)=18.2 (9) kcal mol^?1, entropy (ΔS^≠)=?17.0 (1.4) eu, and energy (E_a)=18.2 (8) kcal mol^?1—suggest a highly organized transition state. Proton scavenging and coordinative probing results suggest that the lanthanide triflates are not simply precursors of free triflic acid. Based on the kinetic and mechanistic evidence, the proposed catalytic pathway invokes hydroxyl and olefin activation by the electron‐deficient Ln³⁺ center, and intramolecular H⁺ transfer, followed by alkoxide nucleophilic attack with ring closure.     

Aromatic and aliphatic CH hydrogen bonds fight for chloride while competing alongside ion pairing within triazolophanes

Triazolophanes are used as the venue to compete an aliphatic propylene CH hydrogen‐bond donor against an aromatic phenylene one. Longer aliphatic C? H ??? Cl^? hydrogen bonds were calculated from the location of the chloride within the propylene‐based triazolophane. The gas‐phase energetics of chloride binding (ΔG_bind, ΔH_bind, ΔS_bind) and the configurational entropy (ΔS_config) were computed by taking all low‐energy conformations into account. Comparison between the phenylene‐ and propylene‐based triazolophanes shows the computed gas‐phase free energy of binding decreased from ΔG_bind=?194 to ?182 kJ mol^?1, respectively, with a modest enthalpy–entropy compensation. These differences were investigated experimentally. An ¹H NMR spectroscopy study on the structure of the propylene triazolophane’s 1:1 chloride complex is consistent with a weaker propylene CH hydrogen bond. To quantify the affinity differences between the two triazolophanes in dichloromethane, it was critical to obtain an accurate binding model. Four equilibria were identified. In addition to 1:1 complexation and 2:1 sandwich formation, ion pairing of the tetrabutylammonium chloride salt (TBA⁺ ? Cl^?) and cation pairing of TBA⁺ with the 1:1 triazolophane–chloride complex were observed and quantified. Each complex was independently verified by ESI‐MS or diffusion NMR spectroscopy. With ion pairing deconvoluted from the chloride–receptor binding, equilibrium constants were determined by using ¹H NMR (500 μM ) and UV/Vis (50 μM ) spectroscopy titrations. The stabilities of the 1:1 complexes for the phenylene and propylene triazolophanes did not differ within experimental error, ΔG=(?38±2) and (?39±1) kJ mol^?1, respectively, as verified by an NMR spectroscopy competition experiment. Thus, the aliphatic CH donor only revealed its weaker character when competing with aromatic CH donors within the propylene‐based triazolophane.     

Influence of basic residues on dissociation kinetics and dynamics of singly protonated peptides: time‐resolved photodissociation study

Product ion yields in postsource decay and time‐resolved photodissociation at 193 and 266 nm were measured for some peptide ions with lysine ([KF₆ + H]⁺, [F₆K + H]⁺, and [F₃KF₃ + H]⁺) formed by matrix‐assisted laser desorption ionization. The critical energy (E₀) and entropy (ΔS^?) were determined by RRKM fitting of the data. The results were similar to those found previously for peptide ions with histidine. To summarize, the presence of a basic residue, histidine or lysine, inside a peptide ion retarded its dissociation by lowering ΔS^?. On the basis of highly negative ΔS^?, presence of intramolecular interaction involving a basic group in the transition structure was proposed. Copyright © 2009 John Wiley & Sons, Ltd.     

Isotope Effects in the Solvolysis of Sterically Hindered Arenesulfonyl Chlorides

Solvent isotope effects in the ethanolysis of sterically hindered arenesulfonyl chlorides ruled out a proton transfer in the rate‐determining step and agreed with a S_N2 mechanism involving at least a second solvent molecule in the transition state (TS). The lack of a secondary kinetic isotope effect in the o‐alkyl groups allows us to disregard the possible contribution of σ–π hyperconjugation. The measured activation parameters are consistent with a S_N2 mechanism involving the participation of solvent molecules in the TS, possibly forming a cyclic TS through a chain of solvent molecules.     

Synthesis,Crystal Structure,Thermal and Explosive Properties of [Cd(SCZ)3(H2O)](PA)2·3H2O (SCZ = Semicarbazide,PA = Picrate)

The heptacoordinate transition metal coordination compound [Cd(SCZ)₃(H₂O)](PA)₂ · 3H₂O ( 1 ) with the ligand semicarbazide (SCZ) and the counteranion picrate (PA) was synthesized and characterized by elemental analysis and FTIR spectroscopy. Single‐crystal X‐ray diffraction analysis revealed that 1 crystallizes in the monoclinic space group P21/c. The Cd²⁺ ion is heptacoordinated by three SCZ groups and a water molecule. SCZ presents typical bidentate coordination modes. The thermal decomposition mechanism of 1 was studied by differential scanning calorimetry (DSC), which revealed that complex 1 exhibits three small endothermic and two large exothermic processes. The non‐isothermal kinetics parameters were calculated by the Kissinger's method and Ozawa‐Doyle's method, respectively. The heat of combustion was measured by oxygen bomb calorimetry. The enthalpy of formation, the critical temperature of thermal explosion, the entropy of activation (ΔS^≠), the enthalpy of activation (ΔH^≠), and the free energy of activation (ΔG^≠) were also calculated. Sensitivity tests revealed that 1 is insensitive to mechanical stimuli.     

Encapsulation of AGE‐Breaker Alagebrium by Cucurbit[7]uril Improved the Stability of Both Its Carbonyl α‐Hydrogen and Thiazolium C2‐Hydrogen

As determined by both ¹H NMR and UV/Vis spectroscopic titration, ESI‐MS, isothermal titration calorimetry, and DFT molecular modeling, advanced glycation end products (AGE) breaker alagebrium (ALA) formed 1:1 guest–host inclusion complexes with cucurbit[7]uril (CB[7]), with a binding affinity, K_a, in the order of magnitude of 10⁵ m ^?1, thermodynamically driven by both enthalpy (ΔH=?6.79 kcal mol^?1) and entropy (TΔS=1.21 kcal mol^?1). For the first time, a dramatic inhibition of keto–enol tautomerism of the carbonyl α‐hydrogen of ALA has been observed, as evidenced by over an order of magnitude decrease of both the first step rate constant, k₁, and the second step rate constant, k₂, during hydrogen/deuterium exchange in D₂O. Meanwhile, as expected, the reactivity of C2‐hydrogen was also inhibited significantly, with an upshift of 2.09 pK_a units. This discovery will not only provide an emerging host molecule to modulate keto–enol tautomerism, but also potentially lead to a novel supramolecular formulation of AGE‐breaker ALA for improved stability and therapeutic efficacy.     

(Nitronyl Nitroxide)‐Substituted Trioxytriphenylamine Radical Cation Tetrachlorogallate Salt: A 2p‐Electron‐Based Weak Ferromagnet Composed of a Triplet Diradical Cation

The synthesis and the solid state magnetic properties of (nitronyl nitroxide)‐substituted trioxytriphenylamine radical cation tetrachlorogallate, NNTOT+·GaCl4? , are reported. In the temperature region between 300 and 3 K, the magnetic behavior is characterized by the strong intramolecular ferromagnetic interaction (J/k_B=+400 K) between the radical ( NN ) and the radical cation ( TOT ⁺) and the weak intermolecular antiferromagnetic interaction (J/k_B=?1.9 K) between NNTOT⁺ ions. Below 3 K, a 3D‐type long‐range magnetic ordering into a weak ferromagnet was observed (T_N=2.65 K). The magnetic entropy (S_mag=8.97 J K^?1 mol^?1) obtained by the heat capacity measurement is in good agreement with the theoretical value of R ln3=9.13 J K^?1 mol^?1 based on the S=1 state.     

Oxidation of Antitubercular Drug Isoniazid by a Lipopathic Oxidant,Cetyltrimethylammonium Dichromate: A Mechanistic Study

The oxidation of an antitubercular drug isoniazid by a lipopathic oxidant cetyltrimethylammonium dichromate (CTADC) in a nonpolar medium generates isonicotinic acid both in the presence and the absence of acetic acid. The conventional UV–vis spectrophotometric method is used to study the reaction kinetics. The occurrence of the Michaelis–Menten–type kinetics with respect to isoniazid confirms the binding of oxidant and substrate to form a complex before the rate‐determining step. The existence of the inverse solvent kinetic isotope effect, k(H₂O)/ k(D₂O) = 0.7, in an acid‐catalyzed reaction proposes a multistep reaction mechanism. A decrease in the rate constant with an increase in [CTADC] reveals the formation of reverse micellar–type aggregates of CTADC in nonpolar solvents. In the presence of different ionic and nonionic surfactants, CTADC forms mixed aggregates and controls the reaction due to the charge on the interface and also due to partition of oxidant and substrate in two different domains. High negative entropy of activation (ΔS^? = –145 and –159 J K^?1 mol^?1 in the absence and presence of acetic acid) proposes a more ordered and highly solvated transition state than the reactants. Furthermore, the solvent polarity‐reactivity relationship reveals (i) the presence of less polar and less ionic transition state compared to the reactants during the oxidation, (ii) differential contribution from nonpolar and dipolar aprotic solvents toward the reaction process, and (iii) the existence of polarity/hydrophobic switch at log P = 0.73. A suitable mechanism has been proposed on the basis of experimental results. These results may provide insight into the mechanism of isoniazid oxidation in hydrophobic environment and may assist in understanding the drug resistance in different location.     

High‐performance liquid chromatographic enantioseparation of isoxazoline‐fused 2‐aminocyclopentanecarboxylic acids on a chiral ligand‐exchange stationary phase

The application of a chiral ligand‐exchange column for the direct high‐performance liquid chromatographic enantioseparation of unusual β‐amino acids with a sodium N‐((R)‐2‐hydroxy‐1‐phenylethyl)‐N‐undecylaminoacetate‐Cu(II) complex as chiral selector is reported. The investigated amino acids were isoxazoline‐fused 2‐aminocyclopentanecarboxylic acid analogs. The chromatographic conditions were varied to achieve optimal separation. The effects of temperature were studied at constant mobile phase compositions in the temperature range 5–45°C, and thermodynamic parameters were calculated from plots of lnk or lnα versus 1/T. Δ(ΔH°) ranged from –2.3 to 2.2 kJ/mol, Δ(ΔS°) from –3.0 to 7.8 J mol^?1 K^?1 and –Δ(ΔG°) from 0.1 to 1.7 kJ/mol, and both enthalpy‐ and entropy‐controlled enantioseparations were observed. The latter was advantageous with regard to the shorter retention and greater selectivity at high temperature. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. The sequence of elution of the enantiomers was determined in all cases.     

SYNTHESIS AND PROPERTIES OF METAL COMPLEXES OF β-DIKETONE BASED SIDE CHAIN LIQUID CRYSTAL POLYSILOXANE

A new type of metal coordinated liquid crystalline polymers has been synthesized by complexation of metal ions with β-diketone based side chain liquid crystal polysiloxane (DKLCP). The complexation of copper ions with DKLCP greatly increases the phase transition temperature T_k from crystalline state to liquid crystalline state and T_(cl) from LC to isotropic state and makes the range of phase transition ΔT (ΔT=T_(cl)-T_k) widened. These complexes are soluble in common organic solvents. However, the incorporation of europium ions into DKLCP molecules gives rise to reduction in liquid crystallinity and crosslinking in some cases. The DKLCP coordinated with suitable amount of Eu ions can show good liquid crystallinity and fluorescent property.     

Studies on the Thermodenaturation Behavior of Bacillus subtilis α‐Amylase on Chromatographic Media

The thermodenaturation behavior of Bacillus subtilis α‐amylase on some chromatographic media was studied by determining their adsorption parameters with frontal analysis. The experimental results show that on a RP‐C₁₈ reversed‐phase medium, a Chelating Sepharose Fast‐Flow chelated by Zn²⁺ affinity medium and a WCX‐1 cation‐exchange medium, a stable conformation of α‐amylase molecule separately exists below or over 30 °C; while on a PEG‐400 hydrophobic medium and a modified PEG‐400 medium, a stable conformation of α‐amylase molecule separately exists below 40 and 30 °C, and when the experimental temperatures are separately over 40 and 30 °C, a drastically conformational change of α‐amylase molecules can continuously take place. And by combining the intrinsic fluorescence emission spectrum and thermal inactivation profile of α‐amylase in free solution and on the PEG‐400 and modified PEG‐400 hydrophobic media, it can be concluded that in liquid chromatographic procedure, chromatographic media can induce the conformational change of α‐amylase molecules and promote their thermodenaturation; and in hydrophobic interaction chromatography, the higher the hydrophobicity of chromatographic medium, the lower the conformational change temperature of α‐amylase molecules on the chromatographic medium.     

Competition between compaction of single chains and bundling of multiple chains in giant DNA molecules

It has been established that in a dilute solution individual giant DNA molecules undergo a large discrete transition between an elongated coil state and a folded compact state. On the other hand, in concentrated solutions, DNA molecules assemble into various characteristic states, including multichain aggregate, liquid crystalline, ionic crystal, etc. In this study, we compared single-chain and multiple-chain events by observing individual chains using fluorescence microscopy. We used spermidine, SPD(3+), as a condensing agent for giant DNA. When the concentration of DNA is below 1 microM in base-pair units, individual DNA molecules exhibit a transition from an elongated state to a compact state. When the concentration of DNA is increased to 10 microM, a thick fiberlike assembly of multiple chains appears. AFM measurements of this thick fiber revealed that more than tens of DNA molecules form a bundle structure with parallel ordering of the chains. The transition between single-chain compaction and bundle formation with multiple-chain assemblies was reproduced by a theoretical calculation.     

Kinetics and mechanism of unimolecular heterolysis of cage-like compounds: XIX. Effect of the nucleofuge nature on the activation parameters of heterolysis of 1-halo-1-methylcyclohexanes in cyclohexane. Heterolysis rate ratio in aprotic and protic solvents

Heterolysis of 1-bromo-1-methylcyclohexane in cyclohexane (E1 reaction) involves solvation of the transition state (ΔS^≡ = ?81 J mol^?1K^?1), while heterolysis of 1-chloro-1-methylcyclohexane is characterized by desolvation of the transition state (ΔS^≡ = 92 J mol^?1K^?1). The probability for the formation of transition state (interaction between cationoid intermediate and solvent cavity) increases in the first case due to enhanced stability of the solvated intermediate, and in the second, due to reduction in its size. The bromide/chloride heterolysis rate ratio decreases as the ionizing power of aprotic solvent decreases and that of protic solvent increases.