Complex-mediated Mechanism Research Articles

Alternating Stereospecificity upon Central-Atom Change: Dynamics of the F- +PH2 Cl SN 2 Reaction Compared to its C- and N-Centered Analogues.

Central-atom effects on bimolecular nucleophilic substitution (SN 2) reactions are well-known in chemistry, however, the atomic-level SN 2 dynamics at phosphorous (P) centers has never been studied. We investigate the dynamics of the F- +PH2 Cl reaction with the quasi-classical trajectory method on a novel full-dimensional analytical potential energy surface fitted on high-level ab initio data. Our computations reveal intermediate dynamics compared to the F- +CH3 Cl and the F- +NH2 Cl SN 2 reactions: phosphorus as central atom leads to a more indirect SN 2 reaction with extensive complex-formation with respect to the carbon-centered one, however, the title reaction is more direct than its N-centered pair. Stereospecificity, characteristic at C-center, does not appear here either, due to the submerged front-side-attack retention path and the repeated entrance-channel inversional motion, whereas the multi-inversion mechanism discovered at nitrogen center is also undermined by the deep Walden-well. At low collision energies, 6 % of the PH2 F products form with retained configuration, mostly through complex-mediated mechanisms, while this ratio reaches 24 % at the highest energy due to the increasing dominance of the direct front-side mechanism and the smaller chance for hitting the deep Walden-inversion minimum. Our results suggest pronounced central-atom effects in SN 2 reactions, which can fundamentally change their (stereo)dynamics.

Promising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight.

Cancer has been progressively a major global health concern. With this developing global concern, cancer determent is one of the most significant public health challenges of this era. To date, the scientific community undoubtedly highlights mitochondrial dysfunction as a hallmark of cancer cells. Permeabilization of the mitochondrial membranes has been implicated as the most considerable footprint in apoptosis-mediated cancer cell death. Under the condition of mitochondrial calcium overload, exclusively mediated by oxidative stress, an opening of a nonspecific channel with a well-defined diameter in mitochondrial membrane allows free exchange between the mitochondrial matrix and the extra mitochondrial cytosol of solutes and proteins up to 1.5 kDa. Such a channel/nonspecific pore is recognized as the mitochondrial permeability transition pore (mPTP). mPTP has been established for regulating apoptosis-mediated cancer cell death. It has been evident that mPTP is critically linked with the glycolytic enzyme hexokinase II to defend cellular death and reduce cytochrome c release. However, elevated mitochondrial Ca2+ loading, oxidative stress, and mitochondrial depolarization are critical factors leading to mPTP opening/activation. Although the exact mechanism underlying mPTP-mediated cell death remains elusive, mPTP-mediated apoptosis machinery has been considered as an important clamp and plays a critical role in the pathogenesis of several types of cancers. In this review, we focus on structure and regulation of the mPTP complex-mediated apoptosis mechanisms and follow with a comprehensive discussion addressing the development of novel mPTP-targeting drugs/molecules in cancer treatment.

Collision-induced and complex-mediated roaming dynamics in the H + C2H4 → H2 + C2H3 reaction.

Roaming is a novel mechanism in reaction dynamics. It describes an unusual pathway, which can be quite different from the conventional minimum-energy path, leading to products. While roaming has been reported or suggested in a number of unimolecular reactions, it has been rarely reported for bimolecular reactions. Here, we report a high-level computational study of roaming dynamics in the important bimolecular combustion reaction H + C2H4 → H2 + C2H3, using a new, high-level machine learning-based potential energy surface. In addition to the complex-mediated roaming mechanism, a non-complex forming roaming mechanism is found. It can be described as a direct inelastic collision where the departing H atom roams and then abstracts an H atom. We denoted this as “collision-induced” roaming. These two roaming mechanisms have different angular distributions; however, both produce highly internally excited C2H3. The roaming pathway leads to remarkably different dynamics as compared with the direct abstraction pathway. A clear signature of the roaming mechanism is highly internally excited C2H3, which could be observed experimentally.

Enhanced strength and ductility in a high-entropy alloy via ordered oxygen complexes.

Oxygen, one of the most abundant elements on Earth, often forms an undesired interstitial impurity or ceramic phase (such as an oxide particle) in metallic materials. Even when it adds strength, oxygen doping renders metals brittle1-3. Here we show that oxygen can take the form of ordered oxygen complexes, a state in between oxide particles and frequently occurring random interstitials. Unlike traditional interstitial strengthening4,5, such ordered interstitial complexes lead to unprecedented enhancement in both strength and ductility in compositionally complex solid solutions, the so-called high-entropy alloys (HEAs)6-10. The tensile strength is enhanced (by 48.5 ± 1.8 per cent) and ductility is substantially improved (by 95.2 ± 8.1 per cent) when doping a model TiZrHfNb HEA with 2.0 atomic per cent oxygen, thus breaking the long-standing strength-ductility trade-off11. The oxygen complexes are ordered nanoscale regions within the HEA characterized by (O, Zr, Ti)-rich atomic complexes whose formation is promoted by the existence of chemical short-range ordering among some of the substitutional matrix elements in the HEAs. Carbon has been reported to improve strength and ductility simultaneously in face-centred cubic HEAs12, by lowering the stacking fault energy and increasing the lattice friction stress. By contrast, the ordered interstitial complexes described here change the dislocation shear mode from planar slip to wavy slip, and promote double cross-slip and thus dislocation multiplication through the formation of Frank-Read sources (a mechanism explaining the generation of multiple dislocations) during deformation. This ordered interstitial complex-mediated strain-hardening mechanism should be particularly useful in Ti-, Zr- and Hf-containing alloys, in which interstitial elements are highly undesirable owing to their embrittlement effects, and in alloys where tuning the stacking fault energy and exploiting athermal transformations13 do not lead to property enhancement. These results provide insight into the role of interstitial solid solutions and associated ordering strengthening mechanisms in metallic materials.

Collision Dynamics of Protonated N-Acetylmethionine with Singlet Molecular Oxygen (a1Δg): The Influence of the Amide Bond and Ruling Out the Complex-Mediated Mechanism at Low Energies

It has been proposed (J. Phys. Chem. B 2011, 115, 2671) that the ammonium group is involved in the gas-phase reaction of protonated methionine (MetH(+)) with singlet oxygen (1)O2, yielding hydrogen peroxide and a dehydro compound of MetH(+) where the -NH3(+) transforms into cyclic -NH2-. For the work reported, the gas-phase reaction of protonated N-acetylmethionine (Ac-MetH(+)) with (1)O2 was examined, including the measurements of reaction products and cross sections over a center-of-mass collision energy (Ecol) range from 0.05 to 1.0 eV using a guided-ion-beam apparatus. The aim is to probe how the acetylation of the ammonium group affects the oxidation chemistry of the ensuing Ac-MetH(+). Properties of intermediates, transition states, and products along the reaction coordinate were explored using density functional theory calculations and Rice-Ramsperger-Kassel-Marcus (RRKM) modeling. Direct dynamics trajectory simulations were carried out at Ecol of 0.05 and 0.1 eV using the B3LYP/4-31G(d) level of theory. In contrast to the highly efficient reaction of MetH(+) + (1)O2, the reaction of Ac-MetH(+) + (1)O2 is extremely inefficient, despite there being exoergic pathways. Two product channels were observed, corresponding to transfer of two H atoms from Ac-MetH(+) to (1)O2 (H2T), and methyl elimination (ME) from a sulfone intermediate complex. Both channels are inhibited by collision energies, becoming negligible at Ecol > 0.2 eV. Analysis of RRKM and trajectory results suggests that a complex-mediated mechanism might be involved at very low Ecol, but direct, nonreactive collisions prevail over the entire Ecol range and physical quenching of (1)O2 occurs during the early stage of collisions.

Complex-mediated growth mechanism of silver nanoparticles–poly(vinyl alcohol) composite nanofibers

In this study, a complex-mediated synthetic growth method was used to embed silver (Ag) nanoparticles in poly(vinyl alcohol) (PVAI) nanofibers in an aqueous solution. Azobisisobutyronitrile (AIBN) played a pivotal role in the preparation of the Ag–PVAI nanofibers, via its cyano groups. AIBN was used to assemble the Ag ions to form Ag complexes in the early stages of the reaction. As the reaction temperature approached 60 °C, AIBN decomposed via breakage of its C–N bonds, and thus the Ag compounds became disassembled. During this stage, Ag nanoparticles were aligned with a PVAI assistant, which acted as a gelator and stabilizer for the formation of fibrous nanostructures under magnetic stirring conditions. As a result, PVAI nanofibers (diameter: ca. 35 nm) were synthesized, with Ag nanoparticles (diameter: ca. 8 nm) embedded compactly in the inner part of the fiber. The formation of Ag–PVAI composite nanofibers was systematically investigated with field-emission scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. Additionally, we performed several control experiments and proposed a plausible mechanism for the synthesis of Ag–PVAI composite nanofibers.

An unusual case of peripheral ulcerative keratitis as a presenting feature in an otherwise healthy patient with undiagnosed human immunodeficiency virus infection and low CD4 counts

Sir, Peripheral ulcerative keratitis (PUK) as initial manifestation in a patient with asymptomatic human immunodeficiency virus (HIV) infection is rarely reported. Herein, we describe HIV vasculitis presenting as PUK in an otherwise healthy HIV-infected patient. A 40-year-old married female presented with right eye redness, blurring of vision and pain since 1 month with no history of trauma, discharge, watering or contact lens wear without any complaints in left eye and no significant systemic history. The best corrected visual acuity was 20/40 and 20/20 in the right and left eyes, respectively. On slit lamp examination, the right eye showed a crescentic lesion involving the nasal corneal margin from 1 to 5 o′clock in the clockwise direction with associated stromal thinning; conjunctival involvement in the form of nodular lesion with dilated tortuous vessels and underlying scleral thinning [Fig. 1]. Ocular adnexa, corneal sensations and dilated fundus examination of both eyes were normal. Figure 1 Right eye showing a crescentic lesion nasally with associated stromal thinning, conjunctival involvement and underlying scleral thinning With an impression of PUK, the patient was advised the following investigations: erythrocyte sedimentation rate (ESR), rheumatoid arthritis factor, antineutophil cytoplasmic antibody, Venereal Disease Research Laboratory test, counselled enzyme-linked immunoassay (ELISA) for HIV, X-ray chest, Mantoux test and rheumatologist opinion. Corneal scraping was subjected to Gram and Giemsa stains, KOH mount and culture and sensitivity, and was reported to be negative. Rheumatology opinion showed no clinical evidence of collagen vascular disorder. All blood investigations, Mantoux test (4 mm induration), ESR (15 mm) and X-ray chest were normal. ELISA for HIV was reported to be positive. The patient was started on lubricant drop and referred to the HIV clinic. CD4 counts (110 cells/cu mm) and viral load by polymerase chain reaction (PCR) (163,960 copies/mL) were done and the patient was started on anti-retroviral therapy (ART) – (zidovudine 300 mg BD, lamivudine 150 mg BD and efavirenz 600 mg OD). Impression cytology of the lesion showed inflammatory cells (neutrophils and lymphocytes) suggesting an active disease process. Scraping was repeated and PCR done for herpes simplex virus 1 and 2 and herpes zoster virus, and was negative. The lesion that initially showed worsening after starting ART (immune recovery response) showed almost complete resolution over the next 2 months, with minimal residual subconjunctival scarring [Fig. 2]. Figure 2 Right eye showing almost complete resolution of the lesion with minimal subconjunctival scarring at 8 weeks follow-up PUK with central retinal vein occlusion[1] and PUK secondary to ocular surface infection with herpes zoster virus[2] have been previously reported in the literature as presenting feature of HIV infection. Our patient had no history of chicken pox, no evidence of herpes zoster or any systemic condition known to be associated with PUK in HIV infection. Vasculities in HIV infection is an uncommon but important pathogenic factor that might manifest as organ-based disease process. HIV vasculopathy is an indirect effect of HIV infection via the immune complex-mediated mechanism or direct infection of vascular/perivascular tissue.[3] Negative serological and microbiological tests, simultaneous involvement of cornea, conjunctiva and sclera,[4] acute inflammatory cells on impression cytology, a high viral load with low CD4 counts and excellent resolution with ART led us to suspect HIV vasculopathy as a possible pathogenesis in our patient. Further research will help us determine the exact pathogenesis in these types of cases.

Dissociative Excitation Energy Transfer in the Reactions of Protonated Cysteine and Tryptophan with Electronically Excited Singlet Molecular Oxygen (a1Δg)

We report a study on the reactions of protonated cysteine (CysH(+)) and tryptophan (TrpH(+)) with the lowest electronically excited state of molecular oxygen (O(2), a(1)Δ(g)), including the measurement of the effects of collision energy (E(col)) on reaction cross sections over the center-of-mass E(col) range of 0.05 to 1.0 eV. Electronic structure calculations were used to examine properties of complexes, transition states and products that might be important along the reaction coordinate. For CysH(+) + (1)O(2), the product channel corresponds to C(α)-C(β) bond rupture of a hydroperoxide intermediate CysOOH(+) accompanied by intramolecular H atom transfer, and subsequent dissociation to H(2)NCHCO(2)H(+), CH(3)SH and ground triplet state O(2). The reaction is driven by the electronic excitation energy of (1)O(2), the so-called dissociative excitation energy transfer. Quasi-classical direct dynamics trajectory simulations were calculated for CysH(+) + (1)O(2) at E(col) = 0.2 and 0.3 eV, using the B3LYP/6-21G method. Most trajectories formed intermediate complexes with significant lifetime, implying the importance of complex formation at the early stage of the reaction. Dissociative excitation energy transfer was also observed in the reaction of TrpH(+) with (1)O(2), leading to dissociation of a TrpOOH(+) intermediate. In contrast to CysOOH(+), TrpOOH(+) dissociates into a glycine molecule and charged indole side chain in addition to ground-state O(2) because this product charge state is energetically favorable. The reactions of CysH(+) + (1)O(2) and TrpH(+) + (1)O(2) present similar E(col) dependence, i.e., strongly suppressed by collision energy and becoming negligible at E(col) > 0.5 eV. This is consistent with a complex-mediated mechanism where a long-lived complex is critical for converting the electronic energy of (1)O(2) to the form of internal energy needed to drive complex dissociation.

Progressive human immunodeficiency virus-associated vasculopathy: time to revise antiretroviral therapy guidelines?

Cardiovascular abnormalities were appreciated early in the epidemic of the acquired immunodeficiency syndrome (AIDS), even before the aetiological agent, human immunodeficiency virus (HIV) was isolated and characterised. The aetiology and pathogenesis of cardiovascular disease in HIV infection is still the subject of intense speculation, and is likely multi-factorial. HIV affects every aspect of the cardiac axis, causing pericarditis, myocarditis, cardiomyopathy, coronary artery disease and microvascular dysfunction, valvular heart disease, pulmonary vascular disease and pulmonary hypertension, stroke and peripheral vascular disease. HIV-associated vasculopathy is an increasingly recognised clinical entity, causing high morbidity and increasing mortality in southern Africa, particularly from stroke and cardiovascular disease. HIV causes disease of the vascular tree, either by a direct effect on vascular or perivascular tissue, or indirectly via immune complex-mediated mechanisms, associated opportunistic infections and malignancies. As a result, highly active antiretroviral therapy (HAART) may have an important role in controlling disease progression. We report a case of histologically defined primary HIV vasculopathy in which the chance to start HAART was initially missed and in which the patient progressed to require bilateral amputations, but obtained disease quiescence upon commencement of HAART.

Systemic Vasculitis in Patients with Hepatitis C Virus Infection with and without Detectable Mixed Cryoglobulinemia

to describe hepatitis C virus (HCV)-related systemic vasculitis in patients without detectable mixed cryoglobulinemia (MC) and to compare them to typical cases of HCV-MC vasculitis. twelve HCV RNA+ patients with histologically proven vasculitis in the absence of detectable MC (cases) were retrospectively compared with 48 HCV RNA+ patients with MC vasculitis (controls). Each case was matched with 4 controls for age and sex. the main epidemiological and virologic features were similar between cases and controls. No clinical difference was found, except for lower rates of arthralgias (33% vs 71%; p = 0.02) and purpura (50% vs 83%; p = 0.03) in cases. Cases showed higher mean serum C3 (1.17 ± 0.21 vs 0.93 ± 0.23 g/l; p = 0.01) and median C4 levels (0.25 vs 0.04 g/l; p < 0.001), lower median serum IgM levels (0.6 vs 1.9 g/l; p < 0.001), and lower rates of rheumatoid factor positivity (8% vs 82%; p < 0.001) than controls. The main histologic features were similar between cases and controls. Immunofluorescence analysis of skin biopsy from 1 case revealed perivascular deposits of C3 and IgA. After treatment, overall clinical response of vasculitis (75% vs 83%) and sustained virological response (40% vs 64%; p = 0.3) were similar between cases and controls, except for higher complete clinical response (42% vs 73%; p = 0.05) in controls. HCV-related systemic vasculitis may occur in the absence of detectable MC. Our findings suggest that such vasculitis probably results from immune complex-mediated mechanisms, and that the therapeutic management of such vasculitis should be similar to that of HCV-MC vasculitis.

Selective regulation of autoreactive B cells by FcγRIIB

FcγRIIB is an inhibitory receptor which plays a role in limiting B cell and DC activation. Since FcγRIIB is known to dampen the signaling strength of the BCR, we wished to determine the impact of FcγRIIB on the regulation of BCRs which differ in their affinity for DNA. For these studies, FcγRIIB deficient BALB/c mice were bred with mice expressing the transgene-encoded H chain of the R4A anti-DNA antibody which gives rise to BCRs which express high, low or no affinity for DNA. The deletion of FcγRIIB in R4A BALB/c mice led to an alteration in the B cell repertoire, allowing for the expansion and activation of high affinity DNA-reactive B cells. By 6–8 months of age, R4A×FcγRIIB−/− BALB/c mice spontaneously developed anti-DNA antibody titers. These mice also displayed an induction of IFN-inducible genes and an elevation in levels of the B cell survival factor, BAFF. These data demonstrate that FcγRIIB preferentially limits activation of high affinity autoreactive B cells and can influence the activation of DC through an immune complex-mediated mechanism.

Imaging Nucleophilic Substitution Dynamics

Anion-molecule nucleophilic substitution (S(N)2) reactions are known for their rich reaction dynamics, caused by a complex potential energy surface with a submerged barrier and by weak coupling of the relevant rotational-vibrational quantum states. The dynamics of the S(N)2 reaction of Cl- + CH3I were uncovered in detail by using crossed molecular beam imaging. As a function of the collision energy, the transition from a complex-mediated reaction mechanism to direct backward scattering of the I- product was observed experimentally. Chemical dynamics calculations were performed that explain the observed energy transfer and reveal an indirect roundabout reaction mechanism involving CH3 rotation.

Acute Renal Failure and Nephrotic Syndrome Associated with Mycoplasma Pneumoniae Pneumonia

A-67-year-old man developed severe hypoxemic pneumonia and acute renal failure with nephrotic syndrome, associated with Mycoplasma pneumoniae infection. Antibody- or immune complex-mediated mechanisms appeared likely, since there was apparent deposition of immunoglobulin (IgM) and complement components (Clq, C3) in the glomeruli, although light microscopy of renal biopsy tissue revealed minor glomerular abnormalities with tubulointerstitial change. The initial antibiotic treatment was not appropriated, therefore possibly allowed the progression of the disease. Early diagnosis and appropriate therapy are essential to the management of Mycoplasma pneumoniae infection

Reaction of formaldehyde cation with molecular hydrogen: effects of collision energy and H2CO+ vibrations.

The effects on the title reaction of collision energy (E(col)) and five H(2)CO(+) vibrational modes have been studied over a center-of-mass E(col) range from 0.1 to 2.3 eV. Electronic structure and Rice-Ramsperger-Kassel-Marcus calculations were used to examine properties of various complexes and transition states that might be important. Only the hydrogen abstraction (HA) product channel is observed, and despite being exoergic, HA has an appearance energy of approximately 0.4 eV, consistent with a transition state found in the electronic structure calculations. A precursor complex-mediated mechanism might possibly be involved at very low E(col), but the dominant mechanism is direct over the entire E(col) range. The magnitude of the HA cross section is strongly, and mode specifically affected by H(2)CO(+) vibrational excitation, however, vibrational energy has no effect on the appearance energy.

Reaction of formaldehyde cation with methane: Effects of collision energy and H2CO+ and methane vibrations

The effects on the title reaction of collision energy (Ecol), five H2CO+ vibrational modes, and deformation vibrations of methane have been studied, including the measurement of product integral and differential cross sections over a center-of-mass Ecol range from 0.09–3.3 eV. Electronic structure and RRKM calculations are reported, providing an additional mechanistic insight. The total reaction efficiency is well below unity, despite there being two exoergic reaction pathways with no activation barriers. The energetically more favorable channel corresponds to H elimination (HE) from an intermediate complex, however, this channel accounts for only ∼15% of the total reaction cross section at low Ecol and is negligible at high energies. The dominant channel, hydrogen abstraction (HA) by H2CO+ from methane, is dominated by a complex-mediated mechanism at low Ecol, switching over to a direct hydrogen-stripping mechanism at high Ecol. Both HA and HE are inhibited in a strongly mode-specific fashion by H2CO+ vibrational excitations, and greatly enhanced by excitation of methane deformation vibrations. The strong mode specificity indicates that the reaction-limiting step occurs early in the collisions.

Charge transfer and chemical reaction dynamics in hyperthermal O++NO collisions

The O+(4S)+NO(X 2Πr) collision system has been investigated in a guided-ion beam experiment. Absolute cross sections for production of NO+ and O2+ have been measured at collision energies from near thermal to ∼12 eV. Time-of-flight measurements of the NO+ product recoil velocities, at collision energies of 1.3, 3.3, 5.2, and 9.1 eV confirm two hyperthermal charge transfer channels with thresholds at 0.2 and 2.0 eV. A kinematic analysis indicates mechanisms that give rise to spin-forbidden NO+(X 1Σ+)+O(1D) and endothermic NO+(a 3Σ+)+O(3P) products, respectively. The O2++N channel is observed to have a threshold of 0.7±0.1 eV. Time-of-flight studies of the O2+ product at collision energies of 3.3 and 5.9 eV indicate a complex-mediated mechanism.

Detailed study of the dynamics of the O+(4S)+ HCN reaction. A case study of ion–molecule reactions in the spacecraft environment

Guided-ion beam (GIB) cross-section and time-of-flight (TOF) measurements are presented for the O+(4S)+ HCN reaction from 0.2–25 eV centre-of-mass (cm) collision energies. The reaction exhibits a charge-transfer and three chemical reaction channels, NO+, CHO+ and CO+. Charge-transfer predominates above ca. 1 eV. The GIB measurements are augmented with selected ion flow tube (SIFT) rate constant measurements at 310 and 485 K. The total SIFT thermal reaction rate coefficients at 310 and 485 K are, 2.5 ± 0.6 × 10–9 cm3 s–1 and 2.3 ± 0.6 × 10–9 cm3 s–1. These values are compared to the 2.0 ± 0.5 × 10–9 cm3 s–1 reaction rate coefficient derived from the 0.2 eV GIB total cross-section.The analysis of the TOF spectra with the osculating complex model reveals that product ion formation is mediated by long-lived intermediate complexes at low collision energies, while a direct mechanism dominates for the majority of the product ions at high energy. Contributions from both direct and complex-mediated mechanisms are observed at intermediate energies. The complex-mediated products show a near-statistical partitioning of reaction energy which is substantiated by a phase-space-theory based calculation. The chemical reaction product branching ratios are discussed in the context of recent ab initio[O—H—C—N]+ hypersurface calculations (A. Luna, A. Mebel and K. Morokuma, personal communication). The application of the measurements to an understanding of atmosphere–spacecraft interactions is also discussed.

Vibrational mode effects, scattering dynamics, and energy disposal in reaction of C2H+2 with methane

The effects of collision energy and mode-selective vibrational excitation on the reaction of C2H+2 with CH4 and CD4 have been measured, along with the corresponding product velocity distributions. Two distinct reaction mechanisms are active in the energy range below 5 eV. At low energies, a long-lived C3H+6 complex forms efficiently, then decomposes primarily to C3H+5+H and C3H+4+H2. The RRKM lifetime of this complex is estimated to range between ∼10 ns and ∼10 ps over the experimental energy range, and this is sufficient time to allow substantial H-atom scrambling. Complex formation is strongly inhibited by collision energy, weakly inhibited by CC stretching, and enhanced by bending excitation. Competing with the complex-mediated mechanism is a direct H-atom abstraction reaction, producing C2H+3+CH3 with little atom scrambling. This reaction is shown to have a ∼150 meV activation barrier and is strongly enhanced by collision energy, becoming the dominant channel above 0.4 eV. CC stretching provides a weaker enhancement than collision energy, while bending enhances the reaction ∼10 times more efficiently. As collision energies increase, the C2H+3 product is increasingly forward scattered with an increasing fraction of the available energy going into recoil. Energy put into reactant vibration mostly is retained as internal energy of the products. Over the collision energy range from 0.4 to 2.8 eV, the collision time in the direct reaction varies from ≥1.3 ps to ≤70 fs.

Enhancement by Fatty Acids of the Rectal Absorption of Propranolol: In Vitro Evaluation in the Rat.

The effects of a series of fatty acids on the rectal absorption of propranolol (PL) were examined in vitro, using macrogol 1500 base and rat rectal tissue. Lauric acid, at a fatty acid: PL molar ratio of 1:1, produced the largest increase in permeation rate (Js), penetration coefficient and partition coefficient of PL. PL flux was increased 2.5-fold in the presence of lauric acid compared to that without the fatty acid. However, the Js value of PL was decreased at increased molar ratios (e.g., 3:1) of lauric acid. The permeation rate of lauric acid across the rectal membrane was much larger than that of PL. Furthermore, the apparent partition coefficient of PL in an n-octanol/buffer system was significantly increased at a 1:1 molar ratio to lauric acid compared with that of PL alone. These results suggest that a complex-mediated mechanism facilitates PL transport, thereby partially contributing to the enhancement of PL rectal absorption. A similar mechanism is applicable to percutaneous drug absorption, as reported previously. Thus, a portion of PL, after first forming a complex with fatty acids, may rapidly permeate across rectal membranes.