Quantum Dynamics of Nonadiabatic Renner-Teller Effects in Atom + Diatom Collisions.

We review the quantum nonadiabatic dynamics of atom + diatom collisions due to the Renner-Teller (RT) effect, i.e., to the Hamiltonian operators that contain the total spinless electronic angular momentum L̂. As is well-known, this rovibronic effect is large near collinear geometries when at least one of the interacting states is doubly degenerate. In general, this occurs in insertion reactions and at short-range, where the potential wells exhibit deep minima and support metastable complexes. Initial-state-resolved reaction probabilities, integral cross sections, and thermal rate constants are calculated via the real wavepacket method, solving the equation of motion with an approximated or with an exact spinless RT Hamiltonian. We present the dynamics of 10 single-channel or multichannel reactions showing how RT effects depend on the product channels and comparing with the Born-Oppenheimer (BO) approximation or coexisting conical-intersection (CI) interactions. RT effects not only can significantly modify the adiabatic dynamics or correct purely CI results, but also they can be very important in opening collision channels which are closed at the BO or CI level, as in electronic-quenching reactions. In the OH(A2Σ+) + Kr electronic quenching, where both nonadiabatic effects (CI and RT) coexist, they are in competition because CI dominates the reactivity but RT couplings reduce the large CI cross section and open a CI-forbidden evolution toward products, so that CI + RT quantum results are in good agreement with experimental or semiclassical findings. The different roles of these couplings are due to the unlike nuclear geometries where they are large: rather far from or near to linearity for CI or RT, respectively. The OH(A2Σ+) + Kr electronic quenching was investigated with the exact RT Hamiltonian, validating the approximated one, which was employed for all other collisions.

Non-adiabatic quantum dynamics of the electronic quenching OH(A2Σ+) + Kr.

We present the dynamics of the electronic quenching OH(A2Σ+) + Kr(1S) → OH(X2Π) + Kr(1S), with OH(A2Σ+) in the ground ro-vibrational state. This study relies on a new non-adiabatic quantum theory that uses three diabatic electronic states Σ+, Π', and Π'', coupled by one conical-intersection and nine Renner-Teller matrix elements, all of which are explicitly considered in the equation of the motion. The time-dependent mechanism and initial-state-resolved quenching probabilities, integral cross sections, thermal rate constants, and thermally-averaged cross sections are calculated via the real wavepacket method. The results point out a competition among three non-adiabatic pathways: Σ+ ↔ Π', Σ+ ↔ Π'', and Π' ↔ Π''. In particular, the conical-intersection effects Σ+-Π' are more important than the Renner-Teller couplings Σ+-Π', Σ+-Π'', and Π'-Π''. Therefore, Π' is the preferred product channel. The quenching occurs via an indirect insertion mechanism, opening many collision complexes, and the probabilities thus present many oscillations. Some resonances are still observable in the cross sections, which are in good agreement with previous experimental and quasi-classical findings. We also discuss the validity of more approximate quantum methods.

Gametocytes from K13 Propeller Mutant Plasmodium falciparum Clinical Isolates Demonstrate Reduced Susceptibility to Dihydroartemisinin in the Male Gamete Exflagellation Inhibition Assay.

Mutations in the kelch propeller domain (K13 propeller) of Plasmodium falciparum parasites from Southeast Asia are associated with reduced susceptibility to artemisinin. We exposed in vitro-cultured stage V gametocytes from Cambodian K13 propeller mutant parasites to dihydroartemisinin and evaluated the inhibition of male gamete formation in an in vitro exflagellation inhibition assay (EIA). Gametocytes with the R539T and C580Y K13 propeller alleles were less susceptible to dihydroartemisinin and had significantly higher 50% inhibitory concentrations (IC50s) than did gametocytes with wild-type alleles.

Dynamics of the O + H2+ → OH+ + H, OH + H+ proton and hydrogen atom transfer reactions on the two lowest potential energy surfaces.

The dynamics of the title reaction was studied using mainly the quasiclassical trajectory (QCT) method on the ground 12A'' (OH+ channel) and first excited 12A' (OH channel) potential energy surfaces (PESs) employing ab initio analytical representations of the PESs developed by us. Both PESs correspond to exoergic reactions, are barrierless and present a deep minimum along the minimum energy path (MEP). Some extra calculations (cross sections) were also performed with the time dependent quantum real wave packet method at the centrifugal sudden level (RWP-CS method). A broad set of properties as a function of collision energy (Ecol ≤ 0.5 eV) was considered using the QCT method: cross sections, average fractions of energy, product rovibrational distributions, two- and three-vector properties, and the microscopic mechanisms analyzing their influence on the dynamics. The proton transfer channel dominates the reactivity of the system and significant differences between the two reaction channels are found for the vibrational distributions and microscopic mechanisms. The results were interpreted according to the properties of the ground and excited PESs. Moreover, the QCT and RWP-CS cross sections are in rather good agreement for both reaction channels. We hope that this study will encourage the experimentalists to investigate the dynamics of this interesting but scarcely studied system, whose two lowest PESs include the ground and first excited electronic states of the H2O+ cation.

Nonadiabatic Renner-Teller quantum dynamics of OH(X2Π) + H+ reactive collisions.

Following previous studies on the O(3P) + H2+(X2Σg+) collisions, we present the nonadiabatic quantum dynamics of the reactions OH(X2Π) + H'+ → OH'(X2Π) + H+, exchange (e), → OH+(X3Σ-) + H'(2S), quenching (q), and → OH'+ (X3Σ-) + H(2S), exchange-quenching (eq). The reactants and products correlate via the ground X[combining tilde]2A'' and first excited Ã2A' electronic states of OH2+, which are the degenerate components of linear 2Π species. Therefore, they are strongly perturbed by nonadiabatic Renner-Teller (RT) effects, opening the (q) and (eq) channels that are closed in the Born-Oppenheimer approximation. Using accurate potential energy surfaces (PESs) and RT matrix elements, initial-state-resolved reaction probabilities, real-time dynamics, cross sections, and rate constants of the product channels are obtained through the time-dependent real wavepacket (WP) method and full coupled-channel calculations. Owing to the nonadiabatic couplings, the WP jumps from the excited Ã2A' surface to the X[combining tilde]2A'' ground PES, avoiding any barrier, opening the quenching channels, and giving many collision complexes into the deep minima of both PESs, as it is clearly shown by the oscillations of the reaction probabilities and by the time-dependent WP dynamics. All the results show that the nonadiabatic-RT channels (q) and (eq) are highly reactive, much more than the adiabatic one (e), pointing out large RT effects. The reactivity of the quenching channels is similar, accounting for 97% of the overall reactivity. In fact, the maximum values of the (q) and (eq) cross sections σq and σeq are equal to 31.6 Å2, whereas the maximum σe value equals 1.34 Å2, and the maximum values of the rate constants kq, keq, and ke are 2.07 × 10-10, 2.45 × 10-10, and 0.23 × 10-10 cm3 s-1. Some calculations show that the centrifugal-sudden and the truncated coupled-channel approximations cannot be employed for the (q) channel. After a sharp increase at the threshold, σq and σeq decrease at larger collision energies while σe and the rate constants depend slightly on the collision energy and temperature, respectively. These findings are consistent with the barrierless nature of both PESs and the exoergicity of the quenching products, with the small role played by the centrifugal and RT barriers in the reactant channel, and with the large RT couplings in the OH2+ intermediates. Finally, we contrast the present results with those for the opposite reactions O + H2+ and for the nonadiabatic-induced quenchings NH + H' and OH + H'.

Unexpectedly large impact of van der Waals interactions on the description of heterogeneously catalyzed reactions: the water gas shift reaction on Cu(321) as a case example.

The molecular mechanisms of the water gas shift reaction on Cu(321) have been chosen to investigate the effect of dispersion terms on the description of the energy profile and reaction rates. The present study based on periodic DFT calculations shows that including dispersion terms does not change the qualitative picture of the overall reaction, maintaining the rate determining step and the predominant route. However, the effect of dispersion is different for different adsorbates - reactants, intermediates or products - with a clear net effect and with no compensation of errors. Thus, in the OH + OH → H2O + O process the dispersion effects imply up to three orders of magnitude in the calculated reaction rates; the formation of carboxyl is highly disfavoured when dispersion terms are explicitly included and finally, the reaction rate for CO2 production (at 463 K) through cis-COOH dissociation is enhanced by three orders of magnitude by including dispersion terms in the calculation of the energy barrier. Consequently, the inclusion of dispersion terms largely affects the overall potential energy profile and produces tremendous changes in the predicted reaction rates. Therefore, dispersion terms must be included when aiming at obtaining information from macroscopic simulations employing for instance microkinetic or kinetic Monte Carlo approaches, where these effects should be clearly shown.

Born-Oppenheimer and Renner-Teller coupled-channel quantum reaction dynamics of O((3)P) + H2(+)(X(2)Σg(+)) collisions.

We present Born-Oppenheimer (BO) and Renner-Teller (RT) time dependent quantum dynamics studies of the reactions O((3)P) + H2(+)(X(2)Σg(+)) → OH(+)(X(3)Σ(-)) + H((2)S) and OH(X(2)Π) + H(+). We consider the OH2(+) X[combining tilde](2)A'' and Ã(2)A' electronic states that correlate with a linear (2)Π species. The electronic angular momenta operators L[combining circumflex] and L[combining circumflex](2) are considered in nonadiabatic coupled-channel calculations, where the associated RT effects are due to diagonal V(RT) potentials that add up to the PESs and to off-diagonal C(RT) couplings between the potential energy surfaces (PESs). Initial-state-resolved reaction probabilities PI, integral cross sections σI, and rate constants kI are obtained using recent ab initio PESs and couplings and the real wavepacket formalism. Because the PESs are strongly attractive, PI have no threshold energy and are large, σI decrease with collision energy, and kI depend little on the temperature. The X[combining tilde](2)A'' PES is up to three times more reactive than the Ã(2)A' PES and H2(+) rotational effects (j0 = 0, 1) are negligible. The diagonal V(RT) potentials are strongly repulsive at the collinearity and nearly halve all low-energy observables with respect to the BO ones. The off-diagonal C(RT) couplings are important at low partial waves, where they mix the X[combining tilde](2)A'' and Ã(2)A' states up to ∼20%. However, V(RT) effects predominate over the C(RT) ones that change at most by ∼19% the BO values of σI and kI. The reaction O((3)P) + H2(+)(X(2)Σg(+)) → OH(+)(X(3)Σ(-)) + H((2)S) is probably one of the most reactive atom + diatom collisions because its RT rate constant at room temperature is equal to 2.26 × 10(-10) cm(3) s(-1). Within the BO approximation, the present results agree rather well with recent quasiclassical and centrifugal-sudden data using the same PESs.

Born-Oppenheimer and Renner-Teller Quantum Dynamics of CH(X(2)Π) + D((2)S) Reactions on Three CHD Potential Surfaces.

The quantum dynamics of three CH(X(2)Π) + D((2)S) reactions is studied by means of the coupled-channel time-dependent real-wavepacket (WP) and flux methods at collision energy Ecol ≤ 0.6 eV and on three potential energy surfaces (PESs): the Born-Oppenheimer (BO) ground PES X̃(3)A″ and the excited ones ã(1)A' and b̃(1)A″, coupled by nonadiabatic (NA) Renner-Teller (RT) effects. This three-state model is suitable for obtaining initial-state-resolved observables, is based on a complete analysis of the correlation diagram of the lowest electronic states of the CHD intermediate and of their NA interactions, and neglects the smaller coupling effects due to the asymptotic electronic angular momenta that become important in state-to-state dynamics. WPs are propagated on each PES at total angular momentum values J ≤ 70, with CH in the two lowest vibrational states v0 and in the ground rotational state j0 = 1. Reaction probabilities are obtained for three possible final products (f): (dP) CH decay and C((3)P) + HD(X(1)Σ(+)) formation that occurs on the uncoupled ground PES, (dD) CH decay and C((1)D) + HD(X(1)Σ(+)) formation that depends on the RT-coupled singlet species, and (ex) exchange to CD(X(2)Π) + H((2)S) available adiabatically from the X̃(3)A″ PES and nonadiabatically from ã(1)A' and b̃(1)A″. Observable cross sections σf,v0j0 and rate constants kf,v0j0 in the temperature range T = 100-2000 K are obtained for (dP), (dD), and (ex) channels. Comparing BO with RT probabilities, we show that NA effects are important at high J values for the (ex) channel at v0 = 1. Real time mechanisms on the three PESs show that RT couplings are opened after some time and clearly point out the formation of the product channels. Both cross sections and rate constants present the same sequence, for example σex,11 > σdP,01 ∼ σex,01 > σdP,11 ≫ σdD,11 ≫ σdD,01, and the CH vibrational excitation enhances the total removal CH+D reactivity by a factor of ∼1.7, mainly due to the increase of the (ex) channel contribution from ∼47% at v0 = 0 to ∼76% at v0 = 1. This fact implies a considerable vibrational enhancement of combustion processes at high temperature. In agreement with the probability results, the ã(1)A'/b̃(1)A″ RT coupling increases both σex,11 and kex,11 up to ∼30%. Moreover, including the three PESs in the dynamics simulation of CH+D increase by far the (ex)/(dP) branching ratio with respect to the CH + H' reaction. Thus, at room temperature, kdP,01 changes from 10.8 × 10(-11) to 3.4 × 10(-11) cm(3) s(-1) substituting H atom by D.

Understanding the effect of vibrational excitation in reaction dynamics: the Ne + H2(+)(v = 0-17, j = 1) → NeH(+) + H, Ne + H(+) + H proton transfer and dissociation cross sections.

The dependence of the cross section (σ) of the Ne + H2(+)→ NeH(+) + H proton transfer reaction on the vibrational excitation of H2(+), v = 0-17 and j = 1, was analyzed in detail at the collision energies (Ecol) of 0.7 and 1.7 eV, using the quasi-classical trajectory (QCT) method and the PHHJ3 and LZHH potential energy surfaces (PESs), taking advantage of the rich experimental data available for this reaction as a function of H2(+)(v). The efficiency of vibrational excitation to promote the reaction was investigated from the analysis of the σ(QCT) vs. v dependence in terms of the average reaction probability, maximum impact parameter, regions of the (late barrier) PES explored, and taking into account the Ne + H2(+)→ Ne + H(+) + H dissociative channel, which plays a dominant role at high enough total energies. Although the earlier PHHJ3 PES performs rather well, the LZHH PES QCT results show a better agreement with the experiment. On the other hand, some artifacts were found in recently reported QCT calculations (unphysical oscillations in σ(QCT) as a function of v), and the present study shows that special care is needed when carrying out QCT calculations involving highly excited vibrational states.

Potential energy surfaces and quasiclassical trajectory study of the O + H2(+)→ OH(+) + H, OH + H(+) proton and hydrogen atom transfer reactions and isotopic variants (D2(+), HD(+)).

The rate constants (k; T: 200-900 K) and cross-sections (σ; Ecol: 0.010-0.50 eV) of the O + H2(+)→ OH(+) + H (1), OH + H(+) (2) reactions, which occur on the ground (1(2)A'') and first excited (1(2)A') potential energy surfaces (PESs), respectively, were investigated for the first time, considering also the rate constants for D2(+) and HD(+). Ab initio multireference configuration interaction calculations were performed on both barrierless PESs (where the minimum energy path involves the insertion of the O atom into the middle of the H2(+) bond), and suitable analytical expressions were developed for the first time and used in quasiclassical trajectory (QCT) calculations. k(1) ≈ 3k(2) independent of the isotopic variant, k(H2(+)) > k(HD(+)) > k(D2(+)) for , and the intermolecular and intramolecular isotopic effects are essentially independent of T. Comparison with the Langevin-Gioumousis-Stevenson (LGS) simple capture model shows that these results are similar to the QCT ones, especially for ; and the isotopic effects are coincident with the QCT ones for both reactions. For O + H2(+), σ(1) ≈ 3σ(2) at Ecol≤ 0.10 eV, and σ(1) = 1.5σ(2) at 0.40 and 0.50 eV. The larger value of σ(1(2)A'') with respect to σ(1(2)A') arises from the larger value of bmax(1(2)A'') with respect to bmax(1(2)A'), and this results from the more attractive character of the former PES. Besides, the reaction probabilities are quite large [0.78-0.98 (1(2)A'') and 0.78-0.93 (1(2)A')], and the decreasing trend of both cross-sections as Ecol increases arises from the barrierless character of both PESs. We expect that these results (in particular, the competition between proton transfer and hydrogen atom transfer) will encourage experimentalists to carry out investigations on this interesting reaction.

Quantum dynamics of the reaction H((2)S) + HeH(+)(X(1)Σ(+)) → H2(+)(X(2)Σg(+)) + He((1)S) from cold to hyperthermal energies: time-dependent wavepacket study and comparison with time-independent calculations.

We present the adiabatic quantum dynamics of the proton-transfer reaction H((2)S) + HeH(+)(X(1)Σ(+)) → H2(+)(X(2)Σg(+)) + He((1)S) on the HeH2(+) X̃(2)Σ(+) RMRCI6 (M = 6) PES of C. N. Ramachandran et al. ( Chem. Phys. Lett. 2009, 469, 26). We consider the HeH(+) molecule in the ground vibrational­rotational state and obtain initial-state-resolved reaction probabilities and the ground-state cross section σ0 and rate constant k0 by propagating time-dependent, coupled-channel, real wavepackets (RWPs) and performing a flux analysis. Three different wavepackets are propagated to describe the wide range of energies explored, from cold (0.0001 meV) to hyperthermal (1000 meV) collision energies, and in a temperature range from 0.01 to 2000 K. We compare our time-dependent results with the time-independent ones by D. De Fazio and S. Bovino et al., where De Fazio carried out benchmark coupled-channel calculations whereas Bovino et al. employed the negative imaginary potential and the centrifugal-sudden approximations. The RWP cross section is in good agreement with that by De Fazio, except at the lowest collision energies below ∼0.01 meV, where the former is larger than the latter. However, neither the RWP and De Fazio results possess the huge resonance in probability and cross section at 0.01 meV, found by Bovino et al., who also obtained a too low σ0 at high energies. Therefore, the RWP and De Fazio rate constants compare quite well, whereas that by Bovino et al. is in general lower.

On the CO2 Harvesting from N2 Using Grazyne Membranes.

The separation of carbon dioxide (CO2) from nitrogen (N2) is at the core of any global warming remediation technology aimed at reducing the CO2 content in the atmosphere. Chemical membranes designed to differentially permeate both molecules have become quite appealing due to their simple use, although many membrane-based separations stand out as a promising solution for CO2 separation. These are environmentally friendly, with high active surface areas, compact design, easy to maintain and cost-effective, although the field is still growing due to the difficulties in the CO2/N2 separation. The present study poses grazynes, two-dimensional C-based materials with sp and sp2 C atoms, aligned along stripes, as suited membranes for the CO2/N2 separation. The combination of density functional theory (DFT) and molecular dynamics (MD) simulations allow tackling the energetics, kinetics, and dynamics of the membrane effectiveness of grazynes with engineered pores for such a separation in a holistic fashion. The explored grazynes are capable of physisorbing CO2 and N2, thus avoiding material poisoning by molecular decoration, while the diffusion of CO2 through the pores is found to be rapid, yet easier than that of N2, in the rate order of the s-1 in the 100-500 K temperature range. In particular, low-temperature CO2 separation even for CO2 contents below 0.5 % are found for [1],[2]{2}-grazyne when controlling the membrane exposure contact to the gas mixture, paving the way for exploring and using grazynes for air CO2 remediation.

Comprehensive Density Functional and Kinetic Monte Carlo Study of CO2 Hydrogenation on a Well-Defined Ni/CeO2 Model Catalyst: Role of Eley-Rideal Reactions.

A detailed multiscale study of the mechanism of CO2 hydrogenation on a well-defined Ni/CeO2 model catalyst is reported that couples periodic density functional theory (DFT) calculations with kinetic Monte Carlo (kMC) simulations. The study includes an analysis of the role of Eley-Rideal elementary steps for the water formation step, which are usually neglected on the overall picture of the mechanism, catalytic activity, and selectivity. The DFT calculations for the chosen model consisting of a Ni4 cluster supported on CeO2 (111) show large enough adsorption energies along with low energy barriers that suggest this catalyst to be a good option for high selective CO2 methanation. The kMC simulations results show a synergic effect between the two 3-fold hollow sites of the supported Ni4 cluster with some elementary reactions dominant in one site, while other reactions prefer the another, nearly equivalent site. This effect is even more evident for the simulations explicitly including Eley-Rideal steps. The kMC simulations reveal that CO is formed via the dissociative pathway of the reverse water-gas shift reaction, while methane is formed via a CO2 → CO → HCO → CH → CH2 → CH3 → CH4 mechanism. Overall, our results show the importance of including the Eley-Rideal reactions and point to small Ni clusters supported on the CeO2 (111) surface as potential good catalysts for high selective CO2 methanation under mild conditions, while very active and selective toward CO formation at higher temperatures.

Resonances in the Ne + H2(+) → NeH(+) + H proton-transfer reaction.

We investigated the oscillations found in the integral cross section of the title reaction, which are particularly evident for Ne + H2(+)(v0 = 2,j0 = 1) [essentially isoenergetic with NeH(+)(v' = 0,j' = 0) + H] at low collision energy (Ecol < 0.30 eV). We employed mainly an exact time-independent (TI) quantum dynamics method and used the best potential energy surface available. From analysis of TI initial state selected to all integral cross sections, state-to-state integral cross sections, and the corresponding differential cross sections (DCSs), we showed that the oscillations correspond to resonances. They arise from the influence of the global [Ne-H-H](+) (collinear) minimum on dynamics and probably correspond to Feshbach resonances. Besides, the forward-backward peaking DCS (which oscillates with Ecol) behavior observed could be a signature for this type of resonances. Finally, as most data on resonances in bimolecular reactions correspond to neutral systems, we hope that the present results will encourage experimentalists to re-examine this benchmark system.

Conical-intersection quantum dynamics of OH(A2Σ+) + H(2S) collisions.

We present the conical-intersection quantum dynamics of the nonreactive quenching (NQ) OH(A(2)Σ(+)) + H'((2)S) → OH(X(2)Π) + H'((2)S), exchange (X) OH(A(2)Σ(+)) + H'((2)S) → OH'(A(2)Σ(+)) + H((2)S), exchange-quenching (XQ) OH(A(2)Σ(+)) + H'((2)S) → OH'(X(2)Π) + H((2)S), and reaction (R) OH(A(2)Σ(+)) + H'((2)S) → O((1)D) + H2(X(1)Σg (+)) collisions. We obtain initial-state-resolved reaction probabilities, cross sections, and rate constants by considering OH in the ground vibrational state and in the rotational levels j0 = 0, 1, 2, and 5. Coupled-channel real wavepackets (WPs) on the X̃(1)A(') and B̃(1)A(') coupled electronic states are propagated by using the Dobbyn and Knowles diabatic potential surfaces and coupling [A. J. Dobbyn and P. J. Knowles, Mol. Phys. 91, 1107 (1997) and A. J. Dobbyn and P. J. Knowles, Faraday Discuss. 110, 207 (1998)], and performing asymptotic or flux analysis. NQ is the preferred product channel, followed by XQ, R, and X. Moreover, the nonadiabatic quenching processes account for more than 80% of the total rate constants. WP snapshots show a reaction mechanism in good agreement with reaction probabilities. NQ, XQ, and R cross sections, and NQ rate constants decrease with the collision energy and j0, whereas the X reactivity increases, and XQ and R rates are nearly constant with j0. In general, quantum rate constants are smaller than experimental or quasiclassical data.

Novel inhibitors that target bacterial virulence identified via HTS against intra-macrophage survival of Shigella flexneri.

Shigella flexneri is a facultative intracellular pathogen that causes shigellosis, a human diarrheal disease characterized by the destruction of the colonic epithelium. Novel antimicrobial compounds to treat infections are urgently needed due to the proliferation of bacterial antibiotic resistance and lack of new effective antimicrobials in the market. Our approach to find compounds that block the Shigella virulence pathway has three potential advantages: (i) resistance development should be minimized due to the lack of growth selection pressure, (ii) no resistance due to environmental antibiotic exposure should be developed since the virulence pathways are not activated outside of host infection, and (iii) the normal intestinal microbiota, which do not have the targeted virulence pathways, should be unharmed. We chose to utilize two phenotypic assays, inhibition of Shigella survival in macrophages and Shigella growth inhibition (minimum inhibitory concentration), to interrogate the 1.7 M compound screening collection subset of the GlaxoSmithKline drug discovery chemical library. A number of secondary assays on the hit compounds resulting from the primary screens were conducted, which, in combination with chemical, structural, and physical property analyses, narrowed the final hit list to 44 promising compounds for further drug discovery efforts. The rapid development of antibiotic resistance is a critical problem that has the potential of returning the world to a "pre-antibiotic" type of environment, where millions of people will die from previously treatable infections. One relatively newer approach to minimize the selection pressures for the development of resistance is to target virulence pathways. This is anticipated to eliminate any resistance selection pressure in environmental exposure to virulence-targeted antibiotics and will have the added benefit of not affecting the non-virulent microbiome. This paper describes the development and application of a simple, reproducible, and sensitive assay to interrogate an extensive chemical library in high-throughput screening format for activity against the survival of Shigella flexneri 2457T-nl in THP-1 macrophages. The ability to screen very large numbers of compounds in a reasonable time frame (~1.7 M compounds in ~8 months) distinguishes this assay as a powerful tool in further exploring new compounds with intracellular effect on S. flexneri or other pathogens with similar pathways of pathogenesis. The assay utilizes a luciferase reporter which is extremely rapid, simple, relatively inexpensive, and sensitive and possesses a broad linear range. The assay also utilized THP-1 cells that resemble primary monocytes and macrophages in morphology and differentiation properties. THP-1 cells have advantages over human primary monocytes or macrophages because they are highly plastic and their homogeneous genetic background minimizes the degree of variability in the cell phenotype (1). The intracellular and virulence-targeted selectivity of our methodology, determined via secondary screening, is an enormous advantage. Our main interest focuses on hits that are targeting virulence, and the most promising compounds with adequate physicochemical and drug metabolism and pharmacokinetic (DMPK) properties will be progressed to a suitable in vivo shigellosis model to evaluate the therapeutic potential of this approach. Additionally, compounds that act via a host-directed mechanism could be a promising source for further research given that it would allow a whole new, specific, and controlled approach to the treatment of diseases caused by some pathogenic bacteria.

Safe drugs with high potential to block malaria transmission revealed by a spleen-mimetic screening.

Malaria parasites like Plasmodium falciparum multiply in red blood cells (RBC), which are cleared from the bloodstream by the spleen when their deformability is altered. Drug-induced stiffening of Plasmodium falciparum-infected RBC should therefore induce their elimination from the bloodstream. Here, based on this original mechanical approach, we identify safe drugs with strong potential to block the malaria transmission. By screening 13 555 compounds with spleen-mimetic microfilters, we identified 82 that target circulating transmissible form of P. falciparum. NITD609, an orally administered PfATPase inhibitor with known effects on P. falciparum, killed and stiffened transmission stages in vitro at nanomolar concentrations. Short exposures to TD-6450, an orally-administered NS5A hepatitis C virus inhibitor, stiffened transmission parasite stages and killed asexual stages in vitro at high nanomolar concentrations. A Phase 1 study in humans with a primary safety outcome and a secondary pharmacokinetics outcome ( https://clinicaltrials.gov , ID: NCT02022306) showed no severe adverse events either with single or multiple doses. Pharmacokinetic modelling showed that these concentrations can be reached in the plasma of subjects receiving short courses of TD-6450. This physiologically relevant screen identified multiple mechanisms of action, and safe drugs with strong potential as malaria transmission-blocking agents which could be rapidly tested in clinical trials.

Theoretical study of the dynamics and kinetics of the O + CS → CO + S chemical laser reaction, where CO shows a very high vibrational excitation.

The dynamics and kinetics of the O((3)P) + CS(X(1)Σ(+)) → CO(X(1)Σ(+)) + S((3)P) chemical laser reaction was studied theoretically in detail for the first time, as a function of collision energy (0.0388-2.0 eV) and rovibrational excitation of CS. This was made using the quasi-classical trajectory (QCT) method and employing the best ab initio analytical ground potential energy surface (1(3)A' PES) available. A broad set of properties was determined, including scalar and vector properties, and the reaction mode. The behaviors observed and the considerable formation of OCS collision complexes were interpreted from some characteristics of the PES (early barrier, shallow minimum in the exit channel, and high exoergicity (mainly channeled into CO vibration; up to ∼81% of the available energy)) and the kinematics. The QCT vibrational and rotational CO populations and the vector properties show a quite good agreement with experiments, but the QCT rate constants disagree. To better account for the kinetics, we performed CASPT2/aug-cc-pVTZ ab initio calculations on the stationary points along the minimum energy path of the ground and first excited (1(3)A'') PESs. The transition state theory, which can be satisfactorily applied here, leads to rate constants (100-2000 K) that are quite close to the measured ones, where comparison is possible (150-300 K). We expect that these results will encourage further theoretical and experimental developments.

Nonadiabatic dynamics of O(1D) + N2(X1Σg+) → O(3P) + N2(X1Σg+) on three coupled potential surfaces: symmetry, Coriolis, spin-orbit, and Renner-Teller effects.

We present the spin-orbit (SO) and Renner-Teller (RT) quantum dynamics of the spin-forbidden quenching O((1)D) + N(2)(X(1)Σ(g)(+)) → O((3)P) + N(2)(X(1)Σ(g)(+)) on the N(2)O X(1)A', ã(3)A", and b(3)A' coupled PESs. We use the permutation-inversion symmetry, propagate coupled-channel (CC) real wavepackets, and compute initial-state-resolved probabilities and cross sections σ(j(0)) for the ground vibrational and the first two rotational states of N(2), j(0) = 0 and 1. Labeling symmetry angular states by j and K, we report selection rules for j and for the minimum K value associated with any electronic state, showing that ã(3)A" is uncoupled in the centrifugal-sudden (CS) approximation at j(0) = 0. The dynamics is resonance-dominated, the probabilities are larger at low K, σ(j(0)) decrease with the collision energy and increase with j(0), and the CS σ(0) is lower than the CC one. The nonadiabatic interactions play different roles on the quenching dynamics, because the X(1)A'-b(3)A' SO effects are those most important while the ã(3)A"-b(3)A' RT ones are negligible.

Effect of Nanoparticles on the Thermal Stability and Reaction Kinetics in Ionic Nanofluids.

Nowadays, the incorporation of nanoparticles into thermal fluids has become one of the most suitable strategies for developing high-performance fluids. An unconventional improvement of thermo-physical properties was observed with the addition of 1% wt. of nanoparticles in different types of fluids, such as molten salts, allowing for the design of more thermally efficient systems using nanofluids. Despite this, there is a lack of knowledge about the effect that nanoparticles produce on the thermal stability and the decomposition kinetics of the base fluid. The present study performs IR- and UV-vis spectroscopy along with thermogravimetric analysis (TGA) of pure nitrate and nitrate based nanofluids with the presence of SiO2 and Al2O3 nanoparticles (1% wt.). The results obtained support that nanoparticles accelerate the nitrate to nitrite decomposition at temperatures below 500 °C (up to 4%), thus confirming the catalytic role of nanoparticles in nanofluids.