Stereodynamical Control of a Quantum Scattering Resonance in Cold Molecular Collisions

Cold collisions of light molecules are often dominated by a single partial wave resonance. For the rotational quenching of HD (v=1, j=2) by collisions with ground state para-H2, the process is dominated by a single L=2 partial wave resonance centered around 0.1 K. Here, we show that this resonance can be switched on or off simply by appropriate alignment of the HD rotational angular momentum relative to the initial velocity vector, thereby enabling complete control of the collision outcome

Insights into functions of the H channel of cytochrome c oxidase from atomistic molecular dynamics simulations

Proton pumping A-type cytochrome c oxidase (CcO) terminates the respiratory chains of mitochondria and many bacteria. Three possible proton transfer pathways (D, K, and H channels) have been identified based on structural, functional, and mutational data. Whereas the D channel provides the route for all pumped protons in bacterial A-type CcOs, studies of bovine mitochondrial CcO have led to suggestions that its H channel instead provides this route. Here, we have studied H-channel function by performing atomistic molecular dynamics simulations on the entire, as well as core, structure of bovine CcO in a lipid-solvent environment. The majority of residues in the H channel do not undergo large conformational fluctuations. Its upper and middle regions have adequate hydration and H-bonding residues to form potential proton-conducting channels, and Asp51 exhibits conformational fluctuations that have been observed crystallographically. In contrast, throughout the simulations, we do not observe transient water networks that could support proton transfer from the N phase toward heme a via neutral His413, regardless of a labile H bond between Ser382 and the hydroxyethylfarnesyl group of heme a. In fact, the region around His413 only became sufficiently hydrated when His413 was fixed in its protonated imidazolium state, but its calculated pK(a) is too low for this to provide the means to create a proton transfer pathway. Our simulations show that the electric dipole moment of residues around heme a changes with the redox state, hence suggesting that the H channel could play a more general role as a dielectric well.Peer reviewe

Light-Regulated Molecular Trafficking in a Synthetic Water-Soluble Host.

Cucurbit[8]uril (CB[8])-mediated complexation of a dicationic azobenzene in water allows for the light-controlled encapsulation of a variety of second guest compounds, including amino acids, dyes, and fragrance molecules. Such controlled guest sequestration inside the cavity of CB[8] enables the regulation of the thermally induced phase transition of poly(N-isopropylacrylamide)-which is not photosensitive-thus demonstrating the robustness and relevancy of the light-regulated CB[8] complexation.J.D.B. thanks Marie Curie IEF (project no. 273807). S.T.J.R. acknowledges the Cambridge Home and European Scholarship Scheme and the Robert Gardiner memorial scholarship. This work was supported by the EPSRC (reference no. EP/G060649/ 1), an ERC Starting Investigator Grant (project no. 240629), and a Next Generation Fellowship from the Walters-Kundert Foundation. The authors thank HECBioSim (EPSRC grant no. EP/L000253/1) via ARCHER, and the Ada King’s HPC3 service.This is the author accepted manuscript. The final version is available from ACS Publications via http://dx.doi.org/10.1021/jacs.5b1164

Stereodynamical control of cold HD + D 2 collisions †

We report full-dimensional quantum calculations of stereodynamic control of HD(v = 1, j = 2) + D2 collisions that has been probed experimentally by Perreault et al. using the Stark-induced adiabatic Raman passage (SARP) technique. Computations were performed on two highly accurate full-dimensional H4 potential energy surfaces. It is found that for both potential surfaces, rotational quenching of HD from with concurrent rotational excitation of D2 from is the dominant transition with cross sections four times larger than that of elastically scattered D2 for the same quenching transition in HD. This process was not considered in the original analysis of the SARP experiments that probed ΔjHD = −2 transitions in HD(vHD = 1, jHD = 2) + D2 collisions. Cross sections are characterized by an l = 3 resonance for ortho-D2(jD2 = 0) collisions, while both l = 1 and l = 3 resonances are observed for the para-D2(jD2 = 1) partner. While our results are in excellent agreement with prior measurements of elastic and inelastic differential cross sections, the agreement is less satisfactory with the SARP experiments, in particular for the transition for which the theoretical calculations indicate that D2 rotational excitation channel is the dominant inelastic process

Antileishmanial activity of terpenylquinones on Leishmania infantum and their effects on Leishmania topoisomerase IB

[EN] Leishmania is the aethiological agent responsible for the visceral leishmaniasis, a serious parasite-borne disease widely spread all over the World. The emergence of resistant strains makes classical treatments less effective; therefore, new and better drugs are necessary. Naphthoquinones are interesting compounds for which many pharmacological properties have been described, including leishmanicidal activity. This work shows the antileishmanial effect of two series of terpenyl-1,4-naphthoquinones (NQ) and 1,4-anthraquinones (AQ) obtained from natural terpenoids, such as myrcene and myrceocommunic acid. They were evaluated both in vitro and ex vivo against the transgenic iRFP-Leishmania infantum strain and also tested on liver HepG2 cells to determine their selectivity indexes. The results indicated that NQ derivatives showed better antileishmanial activity than AQ analogues, and among them, compounds with a diacetylated hydroquinone moiety provided better results than their corresponding quinones. Regarding the terpenic precursor, compounds obtained from the monoterpenoid myrcene displayed good antiparasitic efficiency and low cytotoxicity for mammalian cells, whereas those derived from the diterpenoid showed better antileishmanial activity without selectivity. In order to explore their mechanism of action, all the compounds have been tested as potential inhibitors of Leishmania type IB DNA topoisomerases, but only some compounds that displayed the quinone ring were able to inhibit the recombinant enzyme in vitro. This fact together with the docking studies performed on LTopIB suggested the existence of another mechanism of action, alternative or complementary to LTopIB inhibition. In silico druglikeness and ADME evaluation of the best leishmanicidal compounds has shown good predictable druggabilitySIFinancial support came from Spanish MINECO (CTQ2015-68175-R, AGL2016-79813-C2-1-R, AGL2016-79813-C2-2-R and SAF2017-83575-R), ISCIII-RICET Network (RD12/0018/0002) and Consejería de Educación de la Junta de Castilla y León (LE020P17) co-financed by the Fondo Social Europeo of the European Union (FEDER-EU). P. G. J. acknowledges funding by Fundación Salamanca Ciudad de Cultura y Saberes (’‘Programme for attracting scientific talent to Salamanca’‘