Ion Imaging Experiments Research Articles

Quasi-classical trajectory study of the OH- + CH3I reaction: theory meets experiment.

Regarding OH- + CH3I, several studies have focused on the dynamics of the reaction. Here, high-level quasi-classical trajectory simulations are carried out at four different collision energies on our recently developed potential energy surface. In all, more than half a million trajectories are performed, and for the first time, the detailed quasi-classical trajectory results are compared with the reanalysed crossed-beam ion imaging experiments. Concerning the previously reported direct dynamics study of OH- + CH3I, a better agreement can be obtained between the revised experiment and our novel theoretical results. Furthermore, in the present work, the benchmark geometries, frequencies and relative energies of the stationary points are also determined for the OH- + CH3I proton-abstraction channel along with the earlier characterized SN2 channel.

Ultraviolet photodissociation of Mg+-NO complex: Ion imaging of a reaction branching in the excited states.

Ultraviolet photodissociation processes of gas phase Mg+-NO complex were studied by photofragment ion imaging experiments and theoretical calculations for excited electronic states. At 355nm excitation, both Mg+ and NO+ photofragment ions were observed with positive anisotropy parameters, and theoretical calculations revealed that the two dissociation channels originate from an electronic transition from a bonding orbital consisting of Mg+ 3s and NO π* orbitals to an antibonding counterpart. For the NO+ channel, the photofragment image exhibited a high anisotropy (β = 1.53 ± 0.07), and a relatively large fraction (∼40%) of the available energy was partitioned into translational energy. These observations are rationalized by proposing a rapid dissociation process on a repulsive potential energy surface correlated to the Mg(1S) + NO+(1Σ) dissociation limit. In contrast, for the Mg+ channel, the angular distribution was more isotropic (β = 0.48 ± 0.03) and only ∼25% of the available energy was released into translational energy. The differences in the recoil distribution for these competing channels imply a reaction branching on the excited state surface. On the theoretical potential surface of the excited state, we found a deep well facilitating an isomerization from bent geometry in the Franck-Condon region to linear and/or T-shaped isomer. As a result, the Mg+ fragment was formed via the structural change followed by further relaxation to lower electronic states correlated to the Mg+(2S) + NO(2Π) exit channel.

The TAM-associated STIM1I484R mutation increases ORAI1 channel function due to a reduced STIM1 inactivation break and an absence of microtubule trapping

Tubular aggregate myopathy (TAM) is a progressive skeletal muscle disease associated with gain-of-function mutations in the ER Ca2+ sensor STIM1 that mediates store-operated Ca2+ entry (SOCE) across the Ca2+-release-activated (CRAC) Ca2+ channel ORAI1. A frameshift mutation in STIM1 inactivation domain, STIM1I484R, was identified in a TAM patient and reported to decrease SOCE. Using ion imaging and electrophysiology, we show that the STIM1I484R mutation instead renders STIM1 constitutively active. In ion imaging experiments, STIM1I484R was less efficient than native STIM1 when expressed alone but enhanced SOCE and increased basal Ca2+ and Mn2+ influx when expressed together with ORAI1. In patch-clamp recordings, STIM1I484R generated larger pre-activated CRAC currents lacking slow Ca2+-dependent inhibition (SCDI). STIM1I484R was pre-recruited in plasma membrane clusters when co-expressed with ORAI1, as were mutants truncated at the frameshift residue or lacking EB-1-binding, which recapitulated STIM1I484R gain-of-function. When expressed alone in human primary myoblasts, STIM1I484R was pre-recruited in large clusters and increased basal Ca2+ entry. These observations establish that STIM1I484R confers a gain of CRAC channel function due to the loss of critical inhibitory C-terminal domains that prevent STIM1 binding to ORAI1, enable STIM1 trapping by microtubules, and mediate SCDI, providing a mechanistic explanation for the muscular defects of TAM patients bearing this mutation.

Application of an Event-Based Camera for Real-Time Velocity Resolved Kinetics.

We describe here the application of an inexpensive event-based/neuromorphic camera in an ion imaging experiment operated at 1 kHz detection rate to study real-time velocity-resolved kinetics of thermal desorption. Such measurements involve a single gas pulse to initiate a time-dependent desorption process and a high repetition rate laser, where each pulse of the laser is used to produce an ion image. The sequence of ion images allows the time dependence of the desorption flux to be followed in real time. In previous work where a conventional framing camera was used, the large number of megapixel-sized images required data transfer and storage rates of up to 16 GB/s. This necessitated a large onboard memory that was quickly filled and limited continuous measurement to only a few seconds. Read-out of the memory became the bottleneck to the rate of data acquisition. We show here that since most pixels in each ion image contain no data, the data rate can be dramatically reduced by using an event-based/neuromorphic camera. The data stream is thus reduced to the intensity and location information on the pixels that are lit up by each ion event together with a time-stamp indicating the arrival time of an ion at the detector. This dramatically increases the duty cycle of the method and provides insights for the execution of other high rep-rate ion imaging experiments.

Atomistic dynamics of elimination and nucleophilic substitution disentangled for the F- + CH3CH2Cl reaction.

Chemical reaction dynamics are studied to follow and understand the concerted motion of several atoms while they rearrange from reactants to products. With the number of atoms growing, the number of pathways, transition states, and product channels also increases and rapidly presents a challenge to experiment and theory. Here, we disentangle the competition between bimolecular nucleophilic substitution (SN2) and base-induced elimination (E2) in the polyatomic reaction F- + CH3 CH2 Cl. We find quantitative agreement for the energy- and angle-differential reactive scattering cross sections between ion imaging experiments and quasi-classical trajectory simulations on a 21-dimensional potential energy hypersurface. The anti-E2 pathway is most important, but the SN2 pathway becomes more relevant as the collision energy is increased. In both cases the reaction is dominated by direct dynamics. Our study presents atomic level dynamics of a major benchmark reaction in physical organic chemistry, thereby pushing the number of atoms for detailed reaction dynamics studies to a size that allows applications in many areas of complex chemical networks and environments.

Post extraction inversion slice imaging for 3D velocity map imaging experiments

ABSTRACT An experimental configuration for velocity map ion imaging experiments is presented, in which a pulsed voltage defocusses the ion Newton sphere along the time-of-flight axis. This significantly spreads the times-of-flight for ions with the same mass-to-charge ratio, allowing for either sliced or three-dimensional velocity imaging with high slicing resolution along the time-of-flight axis. The technique is coupled to an event-triggered, position-sensitive sensor, enabling full three-dimensional Newton sphere imaging at high count rates, with significantly improved slicing resolution (∼1–2%) compared to previous DC slicing approaches. Good slice imaging conditions can be brought about at relatively high extraction voltages, circumventing issues regarding image size, stray fields, and poor detection efficiency when operating at low extraction voltages. The method, termed Post Extraction Inversion Slice Imaging (PEISI) was optimised through ion trajectory simulations and experimentally verified on the well-studied photodissociation of OCS at around 230 nm. We demonstrate that this approach is suitable for recording full 3D angular distributions of systems lacking an axis of cylindrical symmetry in the detector plane, where conventional image inversion techniques are invalid. This method could be useful in a range of systems lacking cylindrical symmetry, including studies into angular momentum polarisation and bimolecular scattering.

Photodissociation processes of O2 +(H2O) studied by ion imaging experiments

SynopsisPhotodissociation processes in the visible and ultraviolet region of water-oxygen molecular complex ion, O2 +(H2O), were studied by ion imaging experiments and theoretical calculations. Two fragment ions, H2O+ and O2 +, were observed in the experiment; the former fragment ion was produced by direct dissociation after excitation, whereas the latter was generated by nonadiabatic transitions from the initially excited states to the lower electronic states.

Photodissociation processes of a water-oxygen complex cation studied by an ion imaging technique.

Photochemistry of molecular complex ions in the atmosphere affects the composition, density, and growth of chemical species. Photodissociation processes of a mass-selected O2+(H2O) complex ion in the visible and ultraviolet regions were studied by ion imaging experiments and theoretical calculations. At 473 nm excitation, O2+ was the predominant photofragment ion produced. In this O2+ channel, the kinetic energy release was comparable to that estimated using a statistical dissociation model, and the anisotropy parameter was determined to be β = 1.0 ± 0.1. On the other hand, the H2O+ photofragment ion was mainly produced at 355 nm excitation. The kinetic energy release for the H2O+ channel was large and nonstatistical, and the anisotropy parameter was β = 1.9 ± 0.2. Theoretically, the 473 and 355 nm excitations were assigned to the B[combining tilde]2A''← X[combining tilde]2A'' and D[combining tilde]2A''← X[combining tilde]2A'' transitions, respectively, both of which were characterized by positive charge transfer from O2 to H2O subunits. To further investigate the dissociation mechanisms, potential energy curves (PECs) and surfaces (PESs) for the O2+(H2O) ion were calculated for the ground and excited states. As a result, the H2O+ channel at 355 nm excitation was explained by rapid dissociation on the repulsive PES of the D[combining tilde] state, while rapid electronic relaxation from the B[combining tilde] to X[combining tilde] state followed by dissociation in the ground state was inferred in the O2+ channel at 473 nm excitation.

Visible photodissociation study of NO dimer cation using ion imaging technique combined with theoretical calculations

Visible photodissociation of (NO)2+ at 532–692 nm was investigated by ion imaging experiments and theoretical calculations. From images of photofragment NO+, we obtained the translational energy, which increased with excitation energy. Anisotropy parameter increased from β = 0.7 at 692 nm to 1.4 at 532 nm. These results qualitatively agreed with theoretical calculations, in which (NO)2+ was predicted to be directly dissociated after the C∼←X∼ transition. However, a simple description with an impulsive dissociation model cannot reproduce photon energy dependence of the photofragment energy and angular distributions, implying the importance of multidimensional analyses of potential energy surfaces.

Space-slice ion imaging: High slice resolution imaging in the polarization plane of arbitrarily polarized ionizing light

We present a conceptually new, slit-based slice imaging technique for ion-imaging experiments, offering a way for high slice resolution imaging in the polarization plane of an ionizing laser pulse. In the present method, a mechanically adjustable slit is installed in the drift region of the flight of the ions so that only a thin central slice of a three-dimensionally expanding ion cloud (Newton sphere) passes through the slit. The sliced cloud is then projected onto a two-dimensional position-sensitive ion detector installed parallel to the slice plane. Compared to the conventional two-dimensional imaging, the present “space-slice imaging” scheme has two principle novelties: (1) The slit acts as an ideal gate for the slicing, and a slice resolution of 1% or higher can be achieved, in principle, using submillimeter slit width for a typical a few-centimeter ion cloud. (2) The imaging plane can be automatically parallel to the polarization plane of a laser pulse regardless of the state of polarization, resulting in a hitherto unrealized “camera angle.” We developed a space-slice ion imaging apparatus to realize and validate the present scheme. To evaluate its performance, we carried out the Coulomb explosion imaging of the N2 molecule. By adjusting slit width, slicing up to approximately 0.33% was achieved without remarkable image distortion. The polarization-dependent imaging shows that the ejection angles of ions can be directly read from the observed images obtained with any polarization states. The present imaging measurements in the laser polarization plane opens new avenues for the study of laser-induced dynamics; these dynamics cannot be fully characterized with the existing two-dimensional setups. As an example, we applied the present approach to the time-resolved imaging of a laser-driven rotational wave packet of N2, using a circularly polarized exploding pulse as an isotropic probe in the imaging plane. We successfully observed clear time-dependent images containing full spatiotemporal information of the wave packet dynamics. Details of the concept, design, and operation of our apparatus are presented in the present paper.

Correlation between the velocity scattering angle and product relative translational energy for SN2 reactions. Comparison of experiments and direct dynamics simulations

In previous research, direct dynamics simulations have been used to provide atomistic information for the Cl− + CH3I, F− + CH3I, and OH− + CH3I SN2 and proton transfer (PT) reactions. An important component of these simulations is comparison with molecular beam, ion imaging experiments. From the simulations, comparisons may be made with the product translational energy distributions determined from the experiments and the simulations give quite good agreement with these distributions. Though the experiments provide the in-plane angular distribution for a reaction’s product translational energy distribution, the number of direct dynamics trajectories for a simulation is not sufficient to compare with this angular distribution. In the work presented here, the average percentage product translational energy partitioning for forward scattered events with scattering angle θ = 0–90° and for backward scattered events with θ = 90–180° are compared for the experiments and simulations. Overall good agreement is found, with a maximum difference as high as 5–10%. Additional atomistic details, regarding the dynamics of these reactions, are provided by scatter plots of their product relative translational energy versus the scattering angle θ.

Femtosecond predissociation dynamics of ethyl iodide in the B-band.

Femtosecond time-resolved velocity map ion imaging experiments are reported on the second absorption band (B-band) of ethyl iodide at 201.19 and 200.08 nm, corresponding to the 000 and 1810 transitions, i.e., the origin of the band and the first most intense vibronic state assigned to one quantum of excitation in the methyl torsion mode. Electronic predissociation lifetimes and the temporal evolution of the anisotropy have been determined by time-resolved resonance-enhanced multiphoton ionization of iodine and ethyl fragment images. A shorter lifetime measured at the origin of the band in comparison with methyl iodide indicates that predissociation in ethyl iodide is more favorable due to a stronger coupling between the initial Rydberg state and the valence repulsive state correlating with the dissociation fragments. Moreover, vibrational activity in the methyl torsion in the Rydberg state seems to enhance the probability of transfer of population to the valence repulsive state leading to a faster dissociation. The perpendicular character of the transition at early times and the loss of anisotropy as a function of time have been determined from the time-resolved angular distributions of the iodine and ethyl ion images. The initial anisotropy value is consistent with a purely perpendicular transition compatible with the excitation of the [6A'', 7A'] states with a minor parallel component to the C-I bond. The loss of initial anisotropy over time highlights the parent molecular rotation during predissociation and is compatible with a rotational temperature of the parent molecule of 100 K.

Demonstration of multi-hit and multi-mass capability of 3D imaging in a conventional velocity map imaging experiment.

Coincidence and three-dimensional (3D) imaging offer unique capability in photodissociation and scattering experiments, and a variety of methods have been developed. The basic concept behind all these approaches is to register both the position (x, y) at which the particle hits the detector and the arrival time (t). A novel advance to the time and position sensitive detection was introduced recently by Li and co-workers [Rev. Sci. Instrum. 85(12), 123303 (2014)]. This method utilizes a high-speed digitizer and a computer algorithm along with the camera and detector usually employed in a conventional velocity map imaging apparatus. Due to the normal intensity variations of the ion spots, a correlation can be made between ion intensity recorded by the camera and peak intensity in the digitizer. This makes it possible to associate each ion spot's position with its respective arrival time, thereby constructing a 3D distribution. The technique was primarily introduced for ultrafast ion and electron imaging experiments at high repetition rate with single or few events per image frame. We have recently succeeded in adapting this approach at low repetition rate. Modifications were done to the initial setup to enhance the acquisition efficiency to obtain and correlate multiple hits per laser shot rather than single-hit events. The results are demonstrated in two experiments, dimethyl amine dissociative ionization at 205 nm and carbonyl sulfide photodissociation at 217 nm, with up to 27 events correlated in a single frame. Temporal and spatial slicing capabilities were achieved with good resolution, giving the photofragment velocity and angular distribution for multiple masses simultaneously.

Rovibrationally Excited Molecules on the Verge of a Triple Breakdown: Molecular and Roaming Mechanisms in the Photodecomposition of Methyl Formate.

For the photodissociation of the simplest of esters, methyl formate HCOOCH3, the energy threshold for triple fragmentation into H, CH3O, and CO was measured by previous ion-imaging experiments at a sequence of wavelengths. The translational energy features of product CO in the ground vibrational level (υ = 0) and for selected rotational states were characterized. In this integrated experimental and theoretical approach (i) the focus is at a laser energy barely below that threshold; (ii) Fourier-transform infrared emission spectroscopy measurements probe the rovibrational energy deposition in CO(υ) for υ > 0 and the emergence of the roaming phenomenon; (iii) accompanying quantum chemical calculations describe the selective rupture of bonds; and (iv) molecular dynamics simulations of dissociation are performed, introducing an approach explicitly involving outcomes from paths originated nonadiabatically through conical intersections. Quantitative information on energy disposal is provided: we found extensive vibrational excitation of CO, while rotational bands are colder and bimodal, due to contributions from direct and roaming modes.

Measurement of the density profile of pure and seeded molecular beams by femtosecond ion imaging.

Here, we report on femtosecond ion imaging experiments to measure the density profile of a pulsed supersonic molecular beam. Ion images are measured for both a molecular beam and bulk gas under identical experimental conditions via femtosecond multiphoton ionization of Xe atoms. We report the density profile of the molecular beam, and the measured absolute density is compared with theoretical calculations of the centre line beam density. Subsequently, we discuss reasons accounting for the differences between measurements and calculations and propose that strong skimmer interference is the most probable cause for the differences. Furthermore, we report on experiments measuring the centre line density of seeded supersonic beams. The femtosecond ion images show that seeding the heavy Xe atom at low relative seed fractions (1%-10%) in a light carrier gas like Ne results in strong relative enhancements of up to two orders of magnitude.

Comparison of direct dynamics simulations with different electronic structure methods. F(-) + CH3I with MP2 and DFT/B97-1.

In previous work, ion imaging experiments and direct chemical dynamics simulations with DFT/B97-1 were performed to study the atomic-level dynamics of the F(-) + CH3I → FCH3 + I(-) SN2 nucleophilic substitution reaction at different collision energies. Overall, the simulations are in quite good agreement with experiment at the low collision energy of 0.32 eV, however there are differences between experiment and simulation at the high collision energy of 1.53 eV. A recent CCSD(T) study of the potential energy surface for the F(-) + CH3I → FCH3 + I(-) SN2 reaction shows that it has both a traditional C3v and a hydrogen-bond entrance channel. They are represented by MP2 but not by B97-1, which has only the latter channel. On the other hand, B97-1 gives a reaction exothermicity in excellent agreement with experiment, while MP2 is in error by 24.3 kJ mol(-1). In the work presented here, direct dynamics simulations using MP2/aug-cc-pvdz/ECP/d were performed for the F(-) + CH3I → FCH3 + I(-) reaction at a 1.53 eV collision energy. The same direct rebound and stripping and indirect atomistic reaction mechanisms are found in the B97-1 and MP2 simulations. Both the B97-1 and MP2 simulations agree with the experimental fraction of the available product energy partitioned to CH3F internal energy, i.e. fint = 0.59 ± 0.08. However, the MP2 fint distribution is broader and in better agreement with experiment than B97-1. The two simulations methods give the same product energy partitioning for the stripping mechanism, but different partitionings for the rebound and indirect mechanisms. Compared to experiment, the principal difference between the B97-1 and MP2 results is the differential cross section which is nearly isotropic for B97-1. For MP2 backward scattering is more important than forward, as found in the experiments. Though there is no overall barrier for the reaction, B97-1 gives a reaction cross section appreciably larger than that for MP2, i.e. 8.6 ± 2.2 Å(2)versus 1.8 ± 0.3 Å(2). For B97-1 59% of the reaction consists of indirect mechanisms, while for MP2 the indirect mechanisms only comprise 11% of the reaction. The experimental differential cross section is more consistent with the atomistic mechanisms for MP2 than for B97-1.

Identification of atomic-level mechanisms for gas-phase X- + CH3Y SN2 reactions by combined experiments and simulations.

For the traditional model of gas-phase X(-) + CH3Y SN2 reactions, C3v ion-dipole pre- and postreaction complexes X(-)---CH3Y and XCH3---Y(-), separated by a central barrier, are formed. Statistical intramolecular dynamics are assumed for these complexes, so that their unimolecular rate constants are given by RRKM theory. Both previous simulations and experiments have shown that the dynamics of these complexes are not statistical and of interest is how these nonstatistical dynamics affect the SN2 rate constant. This work also found there was a transition from an indirect, nonstatistical, complex forming mechanism, to a direct mechanism, as either the vibrational and/or relative translational energy of the reactants was increased. The current Account reviews recent collaborative studies involving molecular beam ion-imaging experiments and direct (on-the-fly) dynamics simulations of the SN2 reactions for which Cl(-), F(-), and OH(-) react with CH3I. Also considered are reactions of the microsolvated anions OH(-)(H2O) and OH(-)(H2O)2 with CH3I. These studies have provided a detailed understanding of the atomistic mechanisms for these SN2 reactions. Overall, the atomistic dynamics for the Cl(-) + CH3I SN2 reaction follows those found in previous studies. The reaction is indirect, complex forming at low reactant collision energies, and then there is a transition to direct reaction between 0.2 and 0.4 eV. The direct reaction may occur by rebound mechanism, in which the ClCH3 product rebounds backward from the I(-) product or a stripping mechanism in which Cl(-) strips CH3 from the I atom and scatters in the forward direction. A similar indirect to direct mechanistic transition was observed in previous work for the Cl(-) + CH3Cl and Cl(-) + CH3Br SN2 reactions. At the high collision energy of 1.9 eV, a new indirect mechanism, called the roundabout, was discovered. For the F(-) + CH3I reaction, there is not a transition from indirect to direct reaction as Erel is increased. The indirect mechanism, with prereaction complex formation, is important at all the Erel investigated, contributing up ∼60% of the reaction. The remaining direct reaction occurs by the rebound and stripping mechanisms. Though the potential energy curve for the OH(-) + CH3I reaction is similar to that for F(-) + CH3I, the two reactions have different dynamics. They are akin, in that for both there is not a transition from an indirect to direct reaction. However, for F(-) + CH3I indirect reaction dominates at all Erel, but it is less important for OH(-) + CH3I and becomes negligible as Erel is increased. Stripping is a minor channel for F(-) + CH3I, but accounts for more than 60% of the OH(-) + CH3I reaction at high Erel. Adding one or two H2O molecules to OH(-) alters the reaction dynamics from that for unsolvated OH(-). Adding one H2O molecule enhances indirect reaction at low Erel, and changes the reaction mechanism from primarily stripping to rebound at high Erel. With two H2O molecules the dynamics is indirect and isotropic at all collision energies.

Some preliminary matrix-assisted laser desorption/ionization imaging experiments on maternal and fetal sides of human placenta.

An investigation on placenta proteins has been carried out by matrix-assisted laser desorption/ionization (MALDI) ion imaging (II) experiments. This was performed by laser irradiation of the maternal and fetal sides of placenta tissue. To investigate the possible changes in protein profile due to the development of gestational diabetes mellitus (GDM), five placenta samples from GDM patients and five placenta samples from healthy pregnant women were analyzed. An extensive optimization of the tissue slice treatment and of the matrix deposition method was performed. As already observed in MALDI spectra of placenta homogenates, and also in the MALDI-II condition, the most abundant peaks are due to hemoglobin α chain, hemoglobin β chain and hemoglobin γ chain. However, higher molecular weight protein species were detected in the m/z range 20,000-47,000. The species at m/z 30335, m/z 31235 and m/z 32000 show some differences in their abundance in the maternal and fetal sides of the tissue in both classes of subjects under investigation. Comparison with the literature data suggest that they can result from the presence of mitochondrial proteins at tissue level.

Temperature Dependence of the OH–+ CH3I Reaction Kinetics. Experimental and Simulation Studies and Atomic-Level Dynamics

Direct dynamics simulations and selected ion flow tube (SIFT) experiments were performed to study the kinetics and dynamics of the OH(-) + CH3I reaction versus temperature. This work complements previous direct dynamics simulation and molecular beam ion imaging experiments of this reaction versus reaction collision energy (Xie et al. J. Phys. Chem. A 2013, 117, 7162). The simulations and experiments are in quite good agreement. Both identify the SN2, OH(-) + CH3I → CH3OH + I(-), and proton transfer, OH(-) + CH3I → CH2I(-) + H2O, reactions as having nearly equal importance. In the experiments, the SN2 pathway constitutes 0.64 ± 0.05, 0.56 ± 0.05, 0.51 ± 0.05, and 0.46 ± 0.05 of the total reaction at 210, 300, 400, and 500 K, respectively. For the simulations this fraction is 0.56 ± 0.06, 0.55 ± 0.04, and 0.50 ± 0.05 at 300, 400, and 500 K, respectively. The experimental total reaction rate constant is (2.3 ± 0.6) × 10(-9), (1.7 ± 0.4) × 10(-9), (1.9 ± 0.5) × 10(-9), and (1.8 ± 0.5) × 10(-9) cm(3) s(-1) at 210, 300, 400, and 500 K, respectively, which is approximately 25% smaller than the collision capture value. The simulation values for this rate constant are (1.7 ± 0.2) × 10(-9), (1.8 ± 0.1) × 10(-9), and (1.6 ± 0.1) × 10(-9) cm(3)s(-1) at 300, 400, and 500 K. From the simulations, direct rebound and stripping mechanisms as well as multiple indirect mechanisms are identified as the atomic-level reaction mechanisms for both the SN2 and proton-transfer pathways. For the SN2 reaction the direct and indirect mechanisms have nearly equal probabilities; the direct mechanisms are slightly more probable, and direct rebound is more important than direct stripping. For the proton-transfer pathway the indirect mechanisms are more important than the direct mechanisms, and stripping is significantly more important than rebound for the latter. Calculations were performed with the OH(-) quantum number J equal to 0, 3, and 6 to investigate the effect of OH(-) rotational excitation on the OH(-) + CH3I reaction dynamics. The overall reaction probability and the probabilities for the SN2 and proton-transfer pathways have little dependence on J. Possible effects on the atomistic mechanisms were investigated for the SN2 pathway and the probability of the direct rebound mechanism increased with J. However, the other atomistic mechanisms were not appreciably affected by J.

Human TRPV5 and TRPV6: Key players in cadmium and zinc toxicity

TRPV5 and TRPV6 are two major calcium transport pathways in the human body maintaining calcium homeostasis. TRPV5 is mainly expressed in the distal convoluted and connecting tubule where it is the major, regulated pathway for calcium reabsorption. TRPV6 serves as an important calcium entry pathway in the duodenum and the placenta. Previously, we showed that human TRPV6 (hTRPV6) transports several heavy metals. In this study we tested whether human TRPV5 (hTRPV5) also transports cadmium and zinc, and whether hTRPV5 together with hTRPV6 are involved in cadmium and zinc toxicity. The hTRPV5 mRNA and protein were expressed in HEK293 cells transiently transfected with pTagRFP-C1-hTRPV5. The overexpression of the hTRPV5 protein at the plasma membrane was revealed by cell surface biotinylation and immunofluorescence techniques. We observed that both cadmium and zinc permeate hTRPV5 in ion imaging experiments using Fura-2 or Newport Green DCF. Our results were further confirmed using whole-cell patch clamp technique. Transient overexpression of hTRPV5 or hTRPV6 sensitized cells to cadmium and zinc. Toxicity curves of cadmium and zinc were also shifted in hTRPV6 expressing HEK293 cells clones. Our results suggest that TRPV5 and TRPV6 are crucial gates controlling cadmium and zinc levels in the human body especially under low calcium dietary conditions, when these channels are maximally upregulated.