Equilibrium Constant K1 Research Articles

Self-assembling cobalt(II) porphyrin - fullero [60]pyrrolidine triads. Synthesis and spectral properties in the ground and excited state

Meso‑4-Trifluoromethylphenyl substituted cobalt(II)porphin, CoT(CF3P)P, and its coordination 1: 2 complex (triad) with 1-N-methyl-2-(pyridin-4-yl)-3,4-fullero [60]pyrrolidine, (PyC60)2CoT(CF3P)P, were firstly synthesized and the properties of their molecular solutions were studied. The chemical structure of CoT(CF3P)P and triad was fully confirmed by the UV–vis, IR and 1H NMR spectroscopy and mass spectrometry methods. The triad formation mechanism as the two-step equilibrium characterized by equilibrium constant K1 (5.89 ± 1.50) × 104 M−1 and K2 (7.40 ± 1.66) × 105 M−1 was revealed. Using femtosecond pump-probe spectroscopy measurements, the photoinduced electron transfer in the synthesized triad was described. The excited state lifetime of the precursors, CoTPP, CoT(CF3P)P and the charge separated state lifetime of (PyC60)2CoT(CF3P)P compared with unsubstituted (PyC60)2CoTPP were determined. It was established that the CF3 groups in the porphyrin periphery slightly change the CoTPP/CoT(CF3P)P excited state lifetime and the electron transfer rate constant in the correspondent triads.

Mechanistic analysis of actin-binding compounds that affect the kinetics of cardiac myosin–actin interaction

Actin–myosin mediated contractile forces are crucial for many cellular functions, including cell motility, cytokinesis, and muscle contraction. We determined the effects of ten actin-binding compounds on the interaction of cardiac myosin subfragment 1 (S1) with pyrene-labeled F-actin (PFA). These compounds, previously identified from a small-molecule high-throughput screen (HTS), perturb the structural dynamics of actin and the steady-state actin-activated myosin ATPase activity. However, the mechanisms underpinning these perturbations remain unclear. Here we further characterize them by measuring their effects on PFA fluorescence, which is decreased specifically by the strong binding of myosin to actin. We measured these effects under equilibrium and steady-state conditions, and under transient conditions, in stopped-flow experiments following addition of ATP to S1-bound PFA. We observed that these compounds affect early steps of the myosin ATPase cycle to different extents. They increased the association equilibrium constant K1 for the formation of the strongly bound collision complex, indicating increased ATP affinity for actin-bound myosin, and decreased the rate constant k+2 for subsequent isomerization to the weakly bound ternary complex, thus slowing the strong-to-weak transition that actin–myosin interaction undergoes early in the ATPase cycle. The compounds' effects on actin structure allosterically inhibit the kinetics of the actin–myosin interaction in ways that may be desirable for treatment of hypercontractile forms of cardiomyopathy. This work helps to elucidate the mechanisms of action for these compounds, several of which are currently used therapeutically, and sets the stage for future HTS campaigns that aim to discover new drugs for treatment of heart failure.

Actin-Binding Compounds that Affect the ATP-induced Dissociation of the Actin-Myosin Complex

We previously showed that several actin-binding compounds, discovered by fluorescence-based high-throughput screening (HTS) (Guhathakurta et. al. 2018, JBC 293:12288), affect the fluorescence of pyrene-iodoacetamide labeled F-actin (PIA) both in the presence and absence of cardiac myosin S1 (M) (Roopnarine and Thomas, Biophysical Journal, v116, p119A, 2019). In the latter study, we showed that some of the compounds decreased pyrene-actin fluorescence, suggesting a conformational change in F-actin (A) that increases the solvent exposure of the probe. Some of the compounds prevented full quenching of the pyrene-actin fluorescence by rigor binding of myosin S1 to F-actin, and most of the compounds inhibited full restoration of the pyrene-actin fluorescence that is expected from ATP-induced dissociation of the rigor actin-myosin complex. In the present study, we measured transient kinetics of PIA and myosin S1 using stopped-flow fluorescence to determine the mechanism of action for these compounds. We found that several of these compounds directly decrease the equilibrium constant K1 for the formation of the collision complex (A.M.T) and the rate constant k+2 for the subsequent isomerization to the ternary complex A∼M.T, in which actin is more weakly bound and ATP is more tightly bound. We found that some of the compounds also affect the rate constant for rigor binding of myosin to actin. This work will help to elucidate the mechanism of action of these compounds, several of which are currently used therapeutically, and it sets the stage for future HTS campaigns on a larger scale, to discover new drugs for treatment of heart failure. This work was supported by NIH grants to DDT (R01AR032961, R37AG26160).

Influence of Reaction Reversibility on the Interpretation of Delplots of the Parallel-Series Reaction Network

The use of the Delplot analysis to interpret the experimental results from the parallel-series reaction network A→k1B→k3C; A→k2D under the influence of reaction reversibility was examined. A reactor model was used to test two experimental feeds, one with zero product species concentrations and the other with non-zero product species concentrations. The equilibrium constants K1, K2, and K3 were varied between 0.2 and 1.5 for each reaction in the network. When CA0 = 2.0 M and CB0 = CC0 = CD0 = 0 M, it was found that reversibility did not change the analysis provided by the first-rank Delplots; i.e., species “B” and “D” are primary, while species “C” is non-primary. When CA0 = 2.0 M and CB0 = CC0 = CD0 = 0.5 M, it was found that the effect of the reversibility altered the information provided by Delplot analysis. For instance, the first-rank Delplot classified species “B” as a primary product when K1 ≥ 0.5 but non-primary when K1 = 0.2. A similar conclusion was also obtained for species D; i.e., species “D” ...

Study of the interactions of PAMAM G3-NH2 and G3-OH dendrimers with 5‐fluorouracil in aqueous solutions

The results of spectroscopic measurements (increase in solubility, equilibrium dialysis, 1H NMR titration) and calorimetric measurements (isothermal titration ITC) indicate spontaneous (ΔG<0) bonding of 5‐fluorouracil by both cationic PAMAM G3-NH2 dendrimer and hydroxyl PAMAM G3-OH dendrimer in aqueous solutions. PAMAM G3-NH2 dendrimer bonds about n= 25±8 drug molecules. Some of them n1= 5±1 are bonded by terminal amine groups with equilibrium constant K1= 3890±930, while the remaining ones n2= 24 ±3 are bonded by amide groups with equilibrium constant K2= 110±30. Hydroxyl PAMAM G3-OH dendrimer bonds n=6.0±1.6 molecules of 5-fluorouracil through tertiary amine groups with equilibrium constant K= 65±10. The parameters of bonding 5-fluorouracil by PAMAM G3-NH2 and G3-OH dendrimer were compared with those of bonding this drug by the macromolecules of PAMAM of generations G4-NH2, G5-NH2 and G5-OH.

The Regulation of ATP-Binding, PI Release and ADP Dissociation from Myosin II in Native Cardiac Myofibrils by the N-Terminal Extension of Cardiac Troponin T

Cardiac troponin T (cTnT) has an amino-terminal variable region that plays a role in modifying the overall protein conformation and functions in the calcium-dependent regulation of cardiac muscle contraction. Previous studies have shown that the N-terminal domain of cTnT mainly affects the tropomyosin binding site 1 that binds to the head-tail junction of tropomyosins in thin filament, a moiety involved in the cooperativity of the myofilaments upon calcium activation. It has also been shown that in comparison with wild type controls, transgenic mouse hearts over-expressing cTnT lacking the N-terminal variable region (cTnT-ND) had a decreased rate of contraction, which specifically elongates the rapid ejection phase while keeping total ejection time unchanged, suggesting that the altered cTnT molecule affects the actomyosin crossbridge kinetics. In the present study, we employed stopped flow analysis of mant-ATP binding, ADP dissociation and phosphate release in order to investigate which step(s) of the ATPase cycle is regulated by the N-terminal variable region of cTnT. The results showed that cTnT-ND myofibrils exhibited a maximum mant-ATP binding rate constant (k2) significantly lower than that of WT control, while the equilibrium constant K1 for the initial actomyosin complex formation remained unchanged over calcium concentration. ADP dissociation and Pi release from cTnT-ND myofibrils showed no significant change with increasing calcium concentration, however ADP release is slower in cTnT-ND myofibrils when compared to WT control. These results provide novel information regarding the function of the N-terminal variable region in modulating specific kinetic steps and selectively altering systolic but not diastolic function of the heart.

Oxidation of hydrocarbons and alcohols with peroxides catalyzed by new π-cymene osmium complexes

Two new osmium(II) complexes containing π-coordinated p-cymene (cym) ligands, [(η6-p-cym)Os(bipy)(MeCN)](PF6)2 (1) and (η6-p-cym)Os(py)Cl2 (2) where bipy is 2,2′-bipyridine, have been synthesized. Both complexes efficiently catalyze oxygenation of alkanes (cyclohexane, n-octane, methylcyclohexane, cis- and trans-isomers of 1,2-dimethylcyclohexane), benzene and 1-phenylethanol with hydrogen peroxide in acetonitrile solution in air at 60 °C. Alkanes are oxidized predominantly to alkyl hydroperoxides which can be easily reduced by PPh3 to afford corresponding alcohols. In the cyclohexane oxygenation catalyzed by complex 2 used in a very low concentration (2 × 10−7 M) turnover number (TON) attained 83,000 after 24 h; initial turnover frequency (TOF) was 3400 h−1. The ESI-MS spectrum of the reaction mixture demonstrated the absence of the initial dication [(η6-p-cym)Os(bipy)(MeCN)]2+ which indicates that complex 1 is only a pre-catalyst. Benzene and 1-phenylethanol were transformed into phenol and acetophenone, respectively. The regio- and bond-selectivity parameters measured for the oxidation of linear and branched alkanes and a kinetic analysis of the dependence of initial cyclohexane oxidation rate on concentration of the alkane indicates that the reaction proceeds via attack of hydroxyl radicals at a substrate. The half order of the reaction rate in respect to osmium concentration [Os] can be explained by the assumption that an osmium compound Os introduced into the reaction mixture is rapidly dimerized Os + Os ⇌ D with the equilibrium constant K1. The catalytic activity of the system is due to a monomeric osmium species. The monomer Os forms an adduct with a pyridine molecule (constant K9): Os + py ⇌ Os·py. The interaction with H2O2 affords hydroxyl radicals with rate constant k10. The obtained kinetic data allowed us to estimate values K1/K92 = 520 M and k10 = 1 M−1 s−1.

Prussian blue modified Fe3O4 nanoparticles for Cs detoxification

Fe3O4 nanoparticles were surface modified with Prussian blue (PB) and the nanoparticles were used for the removal of cesium (Cs) ion. The attachment of PB with the Fe3O4 and their morphology were explained based on the studies by transmission electron microscope and BET measurements. The Cs ion adsorption studies have shown that the Cs removal efficiency reached maximum within 120 min. The adsorption kinetics studies using Lagergren pseudo-first-order kinetic model suggest the values of the amount of metal ion adsorbed at equilibrium (qe) and adsorption rate constant (k1) as 22 mg/g and 0.015 min−1, respectively. The capture efficiency of the prepared nanoparticles was studied by varying the flow channel diameter, applied magnetic field, and the fluid flow velocity. The study suggests that PB-Fe3O4 nanoparticles could be used for the detoxification of Cs where the flow velocity is in the range of few tens of cm/s.

Effect of Hydration and Base Contaminants on Sulfuric Acid Diffusion Measurement: A Computational Study

We used quantum chemical formation free energies of hydrated sulfuric acid-containing molecular clusters and a dynamic model to simulate a flow tube measurement, and determined the effective diffusion coefficient of sulfuric acid as a function of relative humidity. This type of measurement was performed by Hanson and Eisele, who presented and applied a fitting method to obtain equilibrium constants K1 and K2 for the formation of sulfuric acid mono- and dihydrates, respectively, from the experimentally determined diffusion coefficients. The fit is derived assuming that only H2SO4 molecules hydrated by up to two water molecules are present. To study the sensitivity of the results to this assumption, we implemented the same fit to the modeled diffusion coefficient data, computed including also larger H2SO4 hydrates with more than two waters. We show that according to quantum chemical equilibrium constants, the larger hydrates are likely to be present in nonnegligible amounts, which affects the effective diff...

Toward a General Mechanism for Transcription Initiation

At the λPR promoter, formation of initiation-competent open complexes involves a series of conformational changes in both RNA polymerase (RNAP) and promoter DNA after initial specific binding. The first set of these changes (described by equilibrium constant K1) bend the downstream duplex DNA into the cleft of RNAP. These reversible steps are followed by the rate-determining step (rate constant k2) in which the DNA is opened in the cleft using binding free energy. This initial open complex is unstable (lifetime ∼1 s) but is greatly stabilized by irreversible conformational changes (quantified by equilibrium constant K3) that reposition the nontemplate strand in the cleft and assemble downstream mobile elements (DME) of RNAP on the downstream duplex DNA, forming RPo (lifetime ∼1 day).In all three phases of this mechanism, large conformational changes in RNAP and/or promoter DNA take place, and allosteric communication occurs over large distances. However, the details are not yet understood for λPR or any other promoter. Are these mechanistic steps universal or promoter-specific? Which steps are the most important targets of regulation by promoter sequence, transcription factors, ligands, and solutes? What determines the efficiency of productive or abortive transcription?To address these questions, we have determined the effects of sequence and length variants of the λPR and T7A1 promoters and several RNAP variants on the kinetics of steps of the initiation mechanism. Taken together, our kinetic data suggest that the early and late steps of the mechanism are the most variable. We therefore propose that these steps are the targets of most cis- and trans-acting regulatory factors, while the opening/closing step is relatively unregulated. This is analogous to many enzyme mechanisms in which most regulation of catalytic velocity occurs in the early and late steps rather than the catalytic step itself.

Solvent-controlled synthesis of tetranuclear cage-like copper(ii) silsesquioxanes. Remarkable features of the cage structures and their high catalytic activity in oxidation with peroxides

Two principally different in their molecular architecture isomeric tetranuclear copper(ii) silsesquioxanes, "Globule"-like compound [(PhSiO1.5)12(CuO)4(NaO0.5)4] (1) and "Sandwich"-like derivative [(PhSiO1.5)6(CuO)4(NaO0.5)4(PhSiO1.5)6] (2), were synthesized by the partial cleavage of polymeric copper(ii) silsesquioxane [(PhSiO1.5)2(CuO)]n by tetraphenylcyclotetrasiloxanolate. The route leading to the formation of either 1 or 2 entirely depends on the nature and composition of the solvent used for this reaction. Thus, the process in an ethanol-1-butanol solution gives compound 1. When a 1,4-dioxane-methanol mixture was used, compound 2 was prepared. The structures and unusual crystal packing of the cages were confirmed by the X-ray studies. It has been found that the reaction of benzene with H2O2 in acetonitrile solution at 50 °C catalyzed by 1 requires addition of trifluoroacetic acid (TFA) in low concentration and gives phenol with a turnover number (TON) of 250 after 3 h. The initial reaction rate W0 linearly depends on the concentration of catalyst 2. The oxidation of 1-phenylethanol to acetophenone with hydrogen peroxide catalyzed by complex 1 in the presence of TFA is not efficient. In contrast, 1 exhibited excellent activity in the oxidation with tert-butyl hydroperoxide (TBHP) in the absence of any acid (the yield of acetophenone was close to the quantitative, TON attained 475 after 2 h). A kinetic study of this reaction led to the conclusion that the process occurs with the participation of radicals tert-BuO˙ produced in the Cu-promoted decomposition of TBHP. The mode of dependence of W0 on the initial concentration of TBHP indicates the formation of an intermediate adduct between the catalyst 1 and TBHP (characterized by the equilibrium constant K1≈ 2 M(-1) for the conditions of conducted experiments) followed by subsequent decomposition of the adduct (k2≈ 0.2 s(-1)) to generate an intermediate species tert-BuO˙ which induces the alcohol oxidation.

Chloroacetonitrile and N,2-Dichloroacetamide Formation from the Reaction of Chloroacetaldehyde and Monochloramine in Water

Combined chlorine is increasingly being used as an alternative disinfectant to free chlorine to maintain a residual in drinking water distribution systems mainly because it would reduce the formation of regulated disinfection byproducts (DBPs) trihalomethanes and haloacetic acids. However, the use of combined chlorine could promote the formation of currently unregulated nitrogenous DBPs (N-DBPs) such as haloacetonitriles and haloacetamides that are found to be more cyto- and genotoxic than regulated DBPs. Monochloramine quickly reacts with chloroacetaldehyde, a DBP formed during primary disinfection with free chlorine, forming and reaching pseudoequilibrium (equilibrium constant K1 = 1.87 × 10(3) M(-1)) with the carbinolamine 2-chloro-1-(chloroamino)ethanol. 2-Chloro-1-(chloroamino)ethanol undergoes slow dehydration to form the imine 1-chloro-2-(chloroimino)ethane that decomposes at a faster rate to chloroacetonitrile. 2-Chloro-1-(chloroamino)ethanol is also oxidized by monochloramine to produce the previously unreported DBP N,2-dichloroacetamide. The carbinolamine dehydration step was found to be acid/base catalyzed (k2(0) = 3.30 × 10(-6) s(-1), k2(H) = 2.43 M(-1) s(-1), k2(OH) = 3.90 M(-1) s(-1)). In contrast, N,2-dichloroacetamide formation was observed to be only base catalyzed (k3(OH) = 3.03 × 10(4) M(-2) s(-1)). N,2-dichloroacetamide cytotoxicity (LC50 = 2.56 × 10(-4) M) was found to be slightly lower compared to that reported for chloroacetamide but higher than those of di- and trichloroacetamide.

Equilibrium between the hydroperoxyl and 1-hydroxycyclohexylperoxyl radicals—Chain carriers in cyclohexanol oxidation with molecular oxygen

The equilibrium constant K2 for the dissociation of the 1-hydroxycyclohexylperoxyl radical to cyclohexanone and the hydroperoxyl radical was determined by the selective inhibition method using nitrobenzene. For cyclohexanol oxidation initiated by cumyl peroxide, (1.6 ± 0.2) × 10−4 mol/L (373 K, ortho-dichlorobenzene).

Calculation of cooperativity and equilibrium constants of ligands binding to G-quadruplex DNA in solution

Equilibrium model of a ligand binding with DNA oligomer has been considered as a process of small molecule adsorption onto a lattice of multiple binding sites. An experimental example has been used to verify the assertion that during saturation of the macromolecule by a ligand should expect effect of cooperativity due to changes in DNA conformation or the mutual influence between bound ligands. Such phenomenon cannot be entirely described by the classical stepwise complex formation model. To evaluate a ligand binding affinity and cooperativity of ligand–oligomer complex formation the statistical approach has been proposed. This new computational approach used to re-examine previously studded ligand binding towards DNA quadruplexes targets with multiple binding sites. The intrinsic equilibrium constants K1−3 of the mesotetrakis-(N-methyl-4-pyridyl)-porphyrin (TMPyP4) binding with the [d(T4G4)]4 and with the [AG3(T2AG3)3] quadruplexes and the correction for the mutual influence between bound ligands (cooperativity parameters ω) was determined from the Job plots based upon the nonlinear least-squares fitting procedure. The re-examination of experimental curves reveals that the equilibrium is affected by the positive cooperative (ω>1) binding of the TMPyP4 ligand with tetramolecular [d(T4G4)]4. However for an intramolecular antiparallel–parallel hybrid structure [AG3(T2AG3)3] the weak anti-cooperativity of TMPyP4 accommodation (ω<1) onto two from three nonidentical sites was detected.

Excess enthalpies of binary mixtures of butylamines + propanols at 298.15 K

The molar excess enthalpies of eight systems of butylamines + propanols were determined at 298.15 K using a twin-microcalorimeter. All excess enthalpies were exothermic and large. An equilibrium constant K 1 expressed in terms of mole fractions and standard thermodynamic properties of formation (Δf H, Δf G, Δf S) of 1:1 complex were evaluated by ideal mixtures of monomeric molecules and their associated complexes. Concentration dependence of the FT-Raman spectrum showed systematic changes of bands. Spectroscopic considerations based on this and ab initio calculations on molecules were performed at the Mp2/6-311G(d,p) level of theory. Interaction energies between butylamine and propanol were calculated by the supermolecular and NBO methods. The results were discussed with previous results to clarify the steric and positional effect of the amino and hydroxyl group.

Novel Activation of Voltage-gated K+ Channels by Sevoflurane

Halogenated inhaled anesthetics modulate voltage-gated ion channels by unknown mechanisms. Biophysical analyses revealed novel activation of K(v) channels by the inhaled anesthetic sevoflurane. K(v) channel activation by sevoflurane results from the positive allosteric modulation of activation gating. The unique activation of K(v) channels by sevoflurane demonstrates novel anesthetic specificity and offers new insights into allosteric modulation of channel gating. Voltage-gated ion channels are modulated by halogenated inhaled general anesthetics, but the underlying molecular mechanisms are not understood. Alkanols and halogenated inhaled anesthetics such as halothane and isoflurane inhibit the archetypical voltage-gated Kv3 channel homolog K-Shaw2 by stabilizing the resting/closed states. By contrast, sevoflurane, a more heavily fluorinated ether commonly used in general anesthesia, specifically activates K-Shaw2 currents at relevant concentrations (0.05-1 mM) in a rapid and reversible manner. The concentration dependence of this modulation is consistent with the presence of high and low affinity interactions (K(D) = 0.06 and 4 mM, respectively). Sevoflurane (<1 mM) induces a negative shift in the conductance-voltage relation and increases the maximum conductance. Furthermore, suggesting possible roles in general anesthesia, mammalian Kv1.2 and Kv1.5 channels display similar changes. Quantitative description of the observations by an economical allosteric model indicates that sevoflurane binding favors activation gating and eliminates an unstable inactivated state outside the activation pathway. This study casts light on the mechanism of the novel sevoflurane-dependent activation of Kv channels, which helps explain how closely related inhaled anesthetics achieve specific actions and suggests strategies to develop novel Kv channel activators.

Esterification equilibrium constants of arsonic and arsinic acids

The esterification equilibrium constants between CD3OD and five arsonic acids (methyl, pentyl, phenyl, 2,3- dipalmitoyloxypropyl, and 2,3,4-tripalmitoyloxybutyl) and one arsinic acid (cacodylic acid) were measured in the solvent system CDCl3/CD3OD at 25.0 C. Equilibrium concentrations of the diester, monoester, and free acid for each compound were calculated from the integrations of the corresponding 1 H NMR peaks. It was found that the nature of the organic part of the arsonic acids essentially did not affect the measured equilibrium constants which were around 0.114 and 0.014 for K1 and K2, respectively. However, the equilibrium constant K1 of cacodylic acid was 0.053. Dies- ters and monoesters are very easily hydrolyzed, and in particular the diesters are extensively hydrolyzed even in the presence of tiny amounts of water. Thus, esters of arsonic or arsinic acids with monohydric alcohols are expected to be in very low concentrations inside cells, a conclusion that may be of interest to the ''arsenic bacterium debate''.

Stoichiometry and equilibrium constant of the complex of PAMAM-NH2 G4 and 5-fluorouracil

Polyamidoamine dendrimer (PAMAM-NH2 G4) complex with 5-fluorouracil, an oncological drug, was investigated by the technique of equilibrium dialysis at temperatures of 20°C and 45°C. The results obtained were worked out by means of the modified model of two sets of active sites proposed by Bobrovnik. Based on the analysis of the results obtained, it was calculated that at a temperature of 20°C the dendrimer molecule can bind about 12 molecules of the ligand with equilibrium constant K1≅5600 and about 37 molecules with equilibrium constant K2≅150. At a temperature of 45°C the number of the dendrimer binding sites is similar but the equilibrium constants of binding 5-fluorouracil with both sets of active sites are clearly lower (K1≅1820, K2≅70). The saturation of both the sets of active sites is of an exothermic character.

Time-Resolved UV-Visible Studies of Rhodopsin Provide Experimental Test of Flexible Surface Model for Lipid-Protein Interactions

Time-resolved UV/Visible absorbance of the retinal chromophore of rhodopsin [1] delivers vital information about key GPCR activation steps in a membrane lipid environment [2]. Following rhodopsin photoexcitation, a minimum of four intermediates equilibrate on the millisecond-time scale [2,3]. The first equilibrium is between the protonated Schiff base (PSB) species Meta I480 and the deprotonated SB species Meta IIa and is pH independent. A second equilibrium entails spectrally silent conversion of Meta IIa to the Meta IIb substate. The final step is protonation of Glu134 of the ERY sequence in Meta IIb to yield Meta IIbH+ whose pKa characterizes the acid-base equilibrium [3]. Absorbance measurements on the microsecond-to-hundred millisecond-time scale allowed us to study effects of POPC, DOPC, or DOPC/DOPE mixtures on the first equilibrium constant K1 and on the pKa of the final equilibrium. Results were analyzed by singular-value decomposition and were fit by a linear combination of temperature-dependent basis spectra. Notably an increase in K1 was discovered due to either PE head groups or increased acyl chain unsaturation, whereas little change in pKawas evident. According to the flexible-surface model (FSM) rhodopsin becomes a sensor of negative spontaneous (intrinsic) curvature upon light activation [4]. Competition between the curvature elastic energy and the hydrophobic mismatch at the proteolipid boundary explains the influences of lipid-protein interactions [4]. Both the lipid acyl chains and polar head groups affect the Meta I-Meta II transition, revealing how protein energetics are affected by material properties of the lipid bilayer.[1] A.V. Struts et al. (2011) Nature Struct. Mol. Biol. 18, 392-394.[2] J. Epps et al. (2006) Photochem. Photobiol. 82, 1436-1441.[3] M. Mahalingam et al. (2008) PNAS 105 17795-17800.[4] A. V. Botelho et al. (2006) Biophys. J. 91, 4464-4477.

Acid-Promoted sp3 C–H Bond Cleavage in a Series of (2-Allylphenoxo)ruthenium(II) Complexes. Mechanistic Insight into the Aryloxo–Acid Interaction and Bond Cleavage Reaction

A series of RuCp[OC6H3(CH2CH═CH2-2)(R)](PPh3)n complexes (n = 2, R = H (1a); n = 1, R = 4-OMe (2b), 4-Me (2c), 4-Ph (2d), 4-Br (2e), 4-NO2 (2f), 6-OMe (2g), 6-Me (2h), 6-Ph (2i)) have been prepared in 27–76% yields. These 2-allylaryloxo complexes 1a and 2b–f are in equilibrium between RuCp[OC6H3(CH2CH═CH2-2)(R)-κ1O](PPh3)2 (1) and RuCp[OC6H3(CH2CH═CH2-2)(R)-κ1O,η2C,C′](PPh3) (2) in solution, and 2g–i do not react with PPh3. The equilibrium constant K1 (K1 = [2][PPh3]/[1]) is about the same for 1a and 2b–f (K1 = 0.07–0.31 M). In contrast to the conventional aryloxo complexes of the late transition metals, treatment of 1a and 2a–g with weak Brϕnsted acids (HOR) gives a rapid equilibrium with 2·HOR. The association constant K2 (K2 = [2·HOR]/([2][HOR])) increases on decreasing the pKa value of the acid employed and on increasing the induction effect of substituents at the 4-position in the aryloxo group. These features suggest present association being regarded as a simple acid–base interaction. Interestingly, further association of 2·HOR with the second acid leads to the cleavage of the benzylic C–H bond, giving RuCp[C3H4{1-C6H3(OH-2)(R)}-η3C,C′,C″](PPh3) (3). The thermodynamic and kinetic studies suggest formation of hydrogen bonds among two Brϕnsted acid molecules, lone-pair electrons in the aryloxo oxygen, and a benzylic methylene proton. Such association makes the Ru(II) center more electrophilic to attack the benzylic carbon to give 3.