Solvent effect on the degree of (a)synchronicity in polar Diels-Alder reactions from the perspective of the reaction force constant analysis

In this work, we computationally evaluated the influence of six different molecular solvents, described as a polarizable continuum model at the M06-2X/6–31+G(d,p) level, on the activation barrier/reaction rate, overall energy change, TS geometry, and degree of (a)synchronicity of two concerted Diels-Alder cycloadditions of acrolein (R1) and its complex with Lewis acid acrolein···BH₃ (R2) to cyclopentadiene. In gas-phase, we found that both exothermicity and activation barrier are only reduced by about 2.0 kcal mol^?1, and the asynchronicity character of the mechanism is accentuated when BH₃ is included. An increment in the solvent’s polarity lowers the activation energy of R1 by 1.3 kcal mol^?1, while for R2 the reaction rate is enhanced by more than 2000 times at room temperature (i.e., the activation energy decreases by 4.5 kcal mol^?1) if the highest polar media is employed. Therefore, a synergistic effect is achieved when both external agents, i.e., Lewis acid catalyst and polar solvent, are included together. This effect was ascribed to the ability of the solvent to favor the encounter between cyclopentadiene and acrolein···BH₃. This was validated by the asymmetry of the TS which becomes highly pronounced when either both or just BH₃ is considered or the solvent’s polarity is increased. Finally, the reaction force constant κ(ξ) reveals that an increment in the solvent’s polarity is able to turn a moderate asynchronous mechanism of the formation of the new C-C σ-bonds into a highly asynchronous one.

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Graphical abstract A synergistic effect is achieved when both external agents, i.e., Lewis acid catalyst and polar solvent, are included together: lowered energy barriers and increased asynchronicities

     

The reaction force and the transition region of a reaction

The reaction force F(R) and the position-dependent reaction force constant κF(R) are defined by F(R)=-∂V(R)/∂R and κ(R)=∂²V(R)/∂R², where V(R) is the potential energy of a reacting system along a coordinate R. The minima and maxima of F(R) provide a natural division of the process into several regions. Those in which F(R) is increasing are where the most dramatic changes in electronic properties take place, and where the system goes from activated reactants (at the force minimum) to activated products (at the force maximum). κ(R) is negative throughout such a region. We summarize evidence supporting the idea that a reaction should be viewed as going through a transition region rather than through a single point transition state. A similar conclusion has come out of transition state spectroscopy. We describe this region as a chemically-active, or electronically-intensive, stage of the reaction, while the ones that precede and follow it are structurally-intensive. Finally, we briefly address the time dependence of the reaction force and the reaction force constant.     

The equilibrium constant of the isocitrate dehydrogenase reaction

1. The equilibrium constant for oxidative decarboxylation of isocitrate by NADP(+), catalysed by isocitrate dehydrogenase, was measured in solutions of various ionic strengths and at several temperatures. 2. Thermodynamic values for the reaction were obtained by extrapolation to zero ionic strength, and the heat of reaction was estimated. 3. The effect of Mg(2+) ion concentration on the equilibrium was studied.     

Protein flexibility from the dynamical transition: a force constant analysis

A standard analysis of the scattered neutron incoherent elastic intensity measured with very good energy resolution yields elastic scans, i.e., mean-square displacements of atomic motions (in a pico to nanosecond time scale) in a sample as a function of temperature. This provides a quick way for characterizing the dynamical behavior of biological macromolecules, such behavior being correlated with biological function and activity. Elastic scans of proteins exhibit a dynamical transition at approximately 200 K, marking a cross-over in molecular fluctuations between harmonic and nonharmonic dynamical regimes. This paper presents an approach allowing analysis of the elastic scan in terms of force constants and related parameters, such as the free energy barrier DeltaG at the transition. We find that the increased protein flexibility beyond the dynamical transition is associated with DeltaG approximately equals RT and effective force constants of the order of 0.1-3 N/m. The analysis provides a set of parameters for characterizing molecular resilience and exploring relations among dynamics, function, and activity in proteins.     

Kinetic studies on the peroxyoxalate chemiluminescence reaction: determination of the cyclization rate constant

Although more currently utilized as analytical tool because of its high sensitivity and good reproducibility, the mechanism of the peroxyoxalate system, a chemiluminescence reaction with quantum yields only comparable to bioluminescence systems, has been extensively studied. The light emission mechanism can be divided in the pathway before chemiexcitation, which contains the rate‐limiting steps, and the fast and kinetically non‐observable chemiexcitation step. In this work, we obtain information on the mechanism of the slow pathways, attribute values to several rate constants prior to chemiexcitation and suggest a mechanistic scheme that could help optimization of conditions when the peroxyoxalate reaction is used as analytical tool. Copyright © 2002 John Wiley & Sons, Ltd.     

Ground reaction force patterns in plyometric push-ups

Compared with lower extremity plyometrics, data concerning the loads and intensity associated with upper extremity plyometrics are limited. The purpose of this study was to compare vertical ground reaction force (vGRF) characteristics between the clap push-up and box drop push-ups from 3.8 cm (BD1), 7.6 cm (BD2), and 11.4 cm (BD3) heights and limbs (dominant, nondominant). Twenty-two healthy active male subjects (age 25.9 ± 1.3 years, height 1.8 ± 0.08 m, mass 87.6 ± 12 kg) performed 4 repetitions of each push-up variation in a random order. Four dependent variables, peak vGRF, time-to-peak vGRF, loading rate (LR), and propulsion rate (PR) were calculated for each extremity. Statistical analysis consisted of separate limb by variation repeated measures analysis of variance. In addition, ground contact time (GCT) was statistically compared between variations. The GCT for the clap push-up (p = 0.033) was significantly less than that for BD1 and BD2. No significant differences were revealed for time-to-peak vGRF (p = 0.717). Peak vGRF was significant between dominant and nondominant limbs (p = 0.045). Post hoc analysis of a significant limb by variation interaction in LR (p < 0.001) revealed the dominant limb to be significantly greater than the nondominant one in all 4 push-up variations. Furthermore, for both limbs, the clap LR was significantly greater than BD1, BD2, and BD3. The clap PR was significantly greater than BD1, BD2, and BD3. These data add rationale for determining upper extremity plyometric progression. The peak vGRFs are similar, and altering the box height did not affect peak vGRF. In contrast, the clap demonstrated the highest LR and PR suggesting that it may be a more powerful exercise than BD1, BD2, and BD3. The higher LR (Clap and BD3) for the dominant extremity illustrates bilateral disparity in the rate of eccentric loading.     

Quantification of equine ground reaction force patterns

A method was developed to quantify the ground reaction force pattern of the horse. A number of selected force amplitudes and peak-time positions in the normalized stance phase of left and right contralateral limbs were used to calculate symmetry indices. Data from each limb were compared with those of a 'standard horse' resulting in limb indices. The combination of amplitude and peak-time symmetry and limb indices yielded one H(orse)INDEX. These indices were useful for comparison of different horses and for the evaluation of lameness and treatment.     

Effects of fatigue on bilateral ground reaction force asymmetries during the squat exercise

Physical performance and injury risk have been related to functional asymmetries of the lower extremity. The effect of fatigue on asymmetries is not well understood. The goal of this investigation was to examine asymmetries during fatiguing repetitions and sets of the free-weight barbell back squat exercise. Seventeen healthy recreationally trained men and women (age = 22.3 ± 2.5 years; body mass = 73.4 ± 13.8 kg; squat 8 repetition maximum [8RM] = 113 ± 35% body mass [mean ± SD]) performed 5 sets of 8 repetitions with 90% 8RM while recording bilateral vertical ground reaction force (GRFv). The GRFv asymmetry during the first 2 (R1 and R2) and the last 2 (R7 and R8) repetitions of each set was calculated by subtracting the % load on the right foot from that of the left foot. Most subjects placed more load on their left foot (also their preferred non-kicking foot). Average absolute asymmetry level across all sets was 4.3 ± 2.5 and 3.6 ± 2.3% for R1 and R2 and R7 and R8, respectively. There were no effects of fatigue on GRFv asymmetries in whole-group analysis (n = 17). However, when initially highly symmetric subjects (±1.7% Left-Right) were removed, average absolute GRFv asymmetry dropped from the beginning to the end of a set (n = 12, p = 0.044) as did peak instantaneous GRFv asymmetry when exploring general shifts toward the left or right leg (n = 12, p = 0.042). The GRFv asymmetries were highly repeatable for 8 subjects that repeated the protocol (Cronbach's α ≥ 0.733, p ≤ 0.056). These results suggest that functional asymmetries, though low, are present in healthy people during the squat exercise and remain consistent. Asymmetries do not increase with fatigue, potentially even decreasing, suggesting that healthy subjects load limbs similarly as fatigue increases, exposing each to similar training stimuli.     

Stretching short sequences of DNA with constant force axial optical tweezers

Single-molecule techniques for stretching DNA of contour lengths less than a kilobase are fraught with experimental difficulties. However, many interesting biological events such as histone binding and protein-mediated looping of DNA, occur on this length scale. In recent years, the mechanical properties of DNA have been shown to play a significant role in fundamental cellular processes like the packaging of DNA into compact nucleosomes and chromatin fibers. Clearly, it is then important to understand the mechanical properties of short stretches of DNA. In this paper, we provide a practical guide to a single-molecule optical tweezing technique that we have developed to study the mechanical behavior of DNA with contour lengths as short as a few hundred basepairs. The major hurdle in stretching short segments of DNA is that conventional optical tweezers are generally designed to apply force in a direction lateral to the stage (see Fig. 1). In this geometry, the angle between the bead and the coverslip, to which the DNA is tethered, becomes very steep for submicron length DNA. The axial position must now be accounted for, which can be a challenge, and, since the extension drags the microsphere closer to the coverslip, steric effects are enhanced. Furthermore, as a result of the asymmetry of the microspheres, lateral extensions will generate varying levels of torque due to rotation of the microsphere within the optical trap since the direction of the reactive force changes during the extension. Alternate methods for stretching submicron DNA run up against their own unique hurdles. For instance, a dual-beam optical trap is limited to stretching DNA of around a wavelength, at which point interference effects between the two traps and from light scattering between the microspheres begin to pose a significant problem. Replacing one of the traps with a micropipette would most likely suffer from similar challenges. While one could directly use the axial potential to stretch the DNA, an active feedback scheme would be needed to apply a constant force and the bandwidth of this will be quite limited, especially at low forces. We circumvent these fundamental problems by directly pulling the DNA away from the coverslip by using a constant force axial optical tweezers. This is achieved by trapping the bead in a linear region of the optical potential, where the optical force is constant-the strength of which can be tuned by adjusting the laser power. Trapping within the linear region also serves as an all optical force-clamp on the DNA that extends for nearly 350 nm in the axial direction. We simultaneously compensate for thermal and mechanical drift by finely adjusting the position of the stage so that a reference microsphere stuck to the coverslip remains at the same position and focus, allowing for a virtually limitless observation period.     

Comparisons of peak ground reaction force and rate of force development during variations of the power clean

The aim of this investigation was to determine the differences in vertical ground reaction forces and rate of force development (RFD) during variations of the power clean. Elite rugby league players (n = 11; age 21 ± 1.63 years; height 181.56 ± 2.61 cm; body mass 93.65 ± 6.84 kg) performed 1 set of 3 repetitions of the power clean, hang-power clean, midthigh power clean, or midthigh clean pull, using 60% of 1-repetition maximum power clean, in a randomized order, while standing on a force platform. Differences in peak vertical ground reaction forces (F(z)) and instantaneous RFD between lifts were analyzed via 1-way analysis of variance and Bonferroni post hoc analysis. Statistical analysis revealed a significantly (p < 0.001) greater peak F(z) during the midthigh power clean (2,801.7 ± 195.4 N) and the midthigh clean pull (2,880.2 ± 236.2 N) compared to both the power clean (2,306.24 ± 240.47 N) and the hang-power clean (2,442.9 ± 293.2 N). The midthigh power clean (14,655.8 ± 4,535.1 N·s?1) and the midthigh clean pull (15,320.6 ± 3,533.3 N·s?1) also demonstrated significantly (p < 0.001) greater instantaneous RFD when compared to both the power clean (8,839.7 ± 2,940.4 N·s?1) and the hang-power clean (9,768.9 ± 4,012.4 N·s?1). From the findings of this study, when training to maximize peak F(z) and RFD the midthigh power clean and midthigh clean pull appear to be the most advantageous variations of the power clean to perform.     

Ground reaction force values in cosmonauts during locomotor exercises on board the International Space Station

Optimal methods for the prevention of negative impact of weightlessness have been developed based on the concept of Kozlovskaya, which states that support afferentation plays a trigger role in the development of the hypogravity motor syndrome. In this study, the maximal vertical ground reaction force (GRF) values were analyzed when locomotor training was performed on a BD-2 treadmill in long-term spaceflights. The study involved 12 cosmonauts. Recorded segments of the locomotor training (4554) performed in active (motor-driven) and passive (non-motor-driven) modes of BD-2 belt motion were analyzed. The data were analyzed by the methods of correlation and regression analysis and the nonparametric Mann–Whitney test. It was found that when running, regardless of the treadmill modes, an increase in the axial load by 1 kg was associated with a more than 1-kg increase in GRF; during walking an increase in GRF was less than 1 kg. As the speed increased, the GRF values increased most quickly when running in a passive mode and most slowly when walking in a passive mode. The GRF values in different BD-2 modes depended on both individual parameters of cosmonauts and locomotion types (walking or running). Our data can be the basis for the individualization of locomotor training onboard the ISS.     

Role of the protein's low dielectric constant in the functioning of the photosynthetic reaction center

The high efficiency of the energy storage in the photosynthetic reaction center (RC) is determined by a successful competition of electron transfer from bacteriopheophytin to quinone, as compared to backward recombination of the primary charge-separated state. This relationship is caused by a fine matching of the reorganization energy and the free energy gap making the forward processes activationless, and hence very fast, and mismatching of these two quantities for the backreaction, therefore retarding it strongly. In this study, we show that this matching is due to a low dielectric constant of the RC's protein core because a low dielectric affects strongly electrostatic polarization components of both the reorganization energy and the equilibrium free energy of reaction. If the protein and membrane were replaced by a homogeneous medium with a high dielectric constant, the effective energy storage would be impractical.     

Experimental analysis of temporomandibular joint reaction force in macaques

Mandibular bone strain in the region immediately below the temporomandibular ligament was analyzed in adult and sub-adult Macaca fascicularis and Macaca mulatta. Following recovery from the general anesthetic, the monkeys were presented food objects, a wooden rod, or a specially designed bite-force transducer. Bone strain was recorded during incisal biting and mastication of food, and also during isometric biting of the rod and/or the transducer. The bone strain data suggest the following: The macaque TMJ is loaded by a compressive reaction force during the power stroke of mastication and incision of food, and during isometric molar and incisor biting. TMJ reaction forces are larger on the contralateral side during both mastication and isometric molar biting. Patterns of ipsilateral TMJ reaction force in macaques during isometric biting vary markedly in response to the position of the bite point. During biting along the premolars or first two molars a compressive reaction force acts about the ipsilateral TMJ; however, when the bite point is positioned along the M3, the ipsilateral TMJ has either very little compressive stress, no stress, or it is loaded in tension.     

The mechanism of methanol decomposition by CuO. A theoretical study based on the reaction force and reaction electronic flux analysis

A theoretical study of methanol decomposition using a model representing the initial step of the reaction CH ₃ OH + CuO → CH ₂ O + H ₂ O + Cu is presented. Theoretical calculations using B3LYP/6-31 G along with Lanl2DZ pseudopotentials on metallic centers were performed and the results discussed within the framework of the reaction force analysis. It has been found that the reaction takes place following a stepwise mechanism: first, copper reduction (Cu ⁺² → Cu ⁺) accompanies the oxygen transposition and then a second reduction takes place (Cu ⁺ → Cu ⁰) together with a proton transfer that produce formaldehyde and release a water molecule.