"Dynamical Docking" of Cyclic Dinuclear Au(I) Bis-N-heterocyclic Complexes Facilitates Their Binding to G-Quadruplexes.

With the aim to improve the design of metal complexes as stabilizers of noncanonical DNA secondary structures, namely, G-quadruplexes (G4s), a series of cyclic dinuclear Au(I) N-heterocyclic carbene complexes based on xanthine and benzimidazole ligands has been synthesized and characterized by various methods, including X-ray diffraction. Fluorescence resonance energy transfer (FRET) and CD DNA melting assays unraveled the compounds' stabilization properties toward G4s of different topologies of physiological relevance. Initial structure-activity relationships have been identified and recognize the family of xanthine derivatives as those more selective toward G4s versus duplex DNA. The binding modes and free-energy landscape of the most active xanthine derivative (featuring a propyl linker) with the promoter sequence cKIT1 have been studied by metadynamics. The atomistic simulations evidenced that the Au(I) compound interacts noncovalently with the top G4 tetrad. The theoretical results on the Au(I) complex/DNA Gibbs free energy of binding were experimentally validated by FRET DNA melting assays. The compounds have also been tested for their antiproliferative properties in human cancer cells in vitro, showing generally moderate activity. This study provides further insights into the biological activity of Au(I) organometallics acting via noncovalent interactions and underlines their promise for tunable targeted applications by appropriate chemical modifications.

Layered Tin Chalcogenides SnS and SnSe: Lattice Thermal Conductivity Benchmarks and Thermoelectric Figure of Merit.

Tin sulfide (SnS) and tin selenide (SnSe) are attractive materials for thermoelectric conversion applications. Favorable small band gap, high carrier mobility, large Seebeck coefficient, and remarkably low lattice thermal conductivity are a consequence of their anisotropic crystal structure of symmetry Pnma , made of corrugated, black phosphorus-like layers. Their internal lattice dynamics combined with chemical bond softening in going from SnS to SnSe make for subtle effects on lattice thermal conductivity. Reliable prediction of phonon transport for these materials must therefore include many-body effects. Using first principles methods and a transferable tight-binding potential for frozen phonon calculations, here, we investigate the evolution of thermal lattice conductivity and thermoelectric figure of merit in Pnma -SnS and -SnSe, also including the high-temperature Cmcm -SnS phase. We show how thermal conductivity lowering in SnS at higher temperatures is largely due to dynamic phonon softening ahead of the Pnma - Cmcm structural phase transition. SnS becomes more similar to SnSe in its lifetime and mean free path profiles as it approaches its high-temperature Cmcm phase. The latter nonetheless intrinsically constraints phonon group velocity modules, preventing SnS to overtake SnSe. Our analysis provides important insights and computational benchmarks for optimization of thermoelectric materials via a more efficient computational strategy compared to previous ab initio attempts, one that can be easily transferred to larger systems for further thermoelectric materials nanoengineering. The good description of anharmonicity at higher temperatures inherent to the tight-binding potential yields calculated lattice conductivity values that are in very good agreement with experiments.

Many-Particle Li Ion Dynamics in LiMPO4 Olivine Phosphates (M = Mn, Fe).

LiMPO4 (M = Mn, Fe) olivine phosphates are important materials for battery applications due to their stability, safety, and reliable recharge cycle. Despite continuous experimental and computational investigations, several aspects of these materials remain challenging, including conductivity dimensionality and how it maps onto Li pathways. In this work, we use a refined version of our finite temperature molecular dynamics "shooting" approach, originally designed to enhance Li hopping probability. We perform a comparative analysis of ion mobility in both materials, focused on many-particle effects. Therein, we identify main [010] diffusion channels, as well as means of interchannel couplings, in the form of Li lateral [001] hopping, which markedly impact the overall mobility efficiency as measured by self-diffusion coefficients. This clearly supports the need of many-particle approaches for reliable mechanistic investigations and for battery materials benchmarking due to the complex nature of the diffusion and transport mechanisms.

Mechanisms of irreversible aquaporin-10 inhibition by organogold compounds studied by combined biophysical methods and atomistic simulations.

The inhibition of glycerol permeation via human aquaporin-10 (hAQP10) by organometallic gold complexes has been studied by stopped-flow fluorescence spectroscopy, and its mechanism has been described using molecular modelling and atomistic simulations. The most effective hAQP10 inhibitors are cyclometalated Au(III) C^N compounds known to efficiently react with cysteine residues leading to the formation of irreversible C-S bonds. Functional assays also demonstrate the irreversibility of the binding to hAQP10 by the organometallic complexes. The obtained computational results by metadynamics show that the local arylation of Cys209 in hAQP10 by one of the gold inhibitors is mapped into a global change of the overall free energy of glycerol translocation across the channel. Our study further pinpoints the need to understand the mechanism of glycerol and small molecule permeation as a combination of local structural motifs and global pore conformational changes, which are taking place on the scale of the translocation process and whose study, therefore, require sophisticated molecular dynamics strategies.

Aquaporin-driven hydrogen peroxide transport: a case of molecular mimicry?

Aquaporins (AQPs) are membrane proteins that have evolved to control cellular water uptake and efflux, and as such are amongst the most ancient biological "devices" in cellular organisms. Recently, using metadynamics, we have shown that water nanoconfinement within aquaporin channels results into bidirectional water movement along single file chains, extending previous investigations. Here, the elusive mechanisms of H2O2 facilitated transport by the human 'peroxiporin' AQP3 has been unravelled via a combination of atomistic simulations, showing that while hydrogen peroxide is able to mimic water during AQP3 permeation, this comes at a certain energy expense due to the required conformational changes within the channel. Furthermore, the intrinsic water dynamics allows for host H2O2 molecule solvation and transport in both directions, highlighting the fundamental role of water nanoconfinement for successful transduction and molecular selection. Overall, the bidirectional nature of the water flux under equilibrium conditions along with the mimicking behavior of hydrogen peroxide during a conductance event introduce a new chemical paradigm never reported so far in any theoretical paper involving any aquaporin isoform.

Unveiling the Mechanisms of Aquaglyceroporin-3 Water and Glycerol Permeation by Metadynamics.

Water and glycerol permeation through human AQP3 are described by exploiting advanced metadynamics approaches, which enabled both to explore the free energies involved in pore permeation and to achieve a description of the mechanisms with an atomistic level of detail.

Molecular Basis of Aquaporin-7 Permeability Regulation by pH.

The aquaglyceroporin AQP7, a family member of aquaporin membrane channels, facilitates the permeation of water and glycerol through cell membranes and is crucial for body lipid and energy homeostasis. Regulation of glycerol permeability via AQP7 is considered a promising therapeutic strategy towards fat-related metabolic complications. Here, we used a yeast aqy-null strain for heterologous expression and functional analysis of human AQP7 and investigated its regulation by pH. Using a combination of in vitro and in silico approaches, we found that AQP7 changes from fully permeable to virtually closed at acidic pH, and that Tyr135 and His165 facing the extracellular environment are crucial residues for channel permeability. Moreover, instead of reducing the pore size, the protonation of key residues changes AQP7's protein surface electrostatic charges, which, in turn, may decrease glycerol's binding affinity to the pore, resulting in decreased permeability. In addition, since some pH-sensitive residues are located at the monomer-monomer interface, decreased permeability may result from cooperativity between AQP7's monomers. Considering the importance of glycerol permeation via AQP7 in multiple pathophysiological conditions, this mechanism of hAQP7 pH-regulation may help the design of selective modulators targeting aquaglyceroporin-related disorders.

Templated Chromophore Assembly on Peptide Scaffolds: A Structural Evolution.

The use of a template that bears pre-programmed receptor sites for selectively accommodating chromophores at given positions is an attractive approach for engineering artificial-light-harvesting systems. Indulging this line of thought, this work tackles the creation of tailored antenna architectures with yellow, red and blue chromophores, exploiting three dynamic covalent reactions simultaneously, namely disulfide exchange, acyl hydrazone, and boronic ester formations. The effect of various structural modifications, such as the chromophores as well as their spatial organization (distance, orientation, order) on the energy transfer within the antennas was studied by means of steady-state UV/Vis absorption and fluorescence spectroscopies. This systematic study allowed for a significant improvement of the energy-transfer efficiencies to a noticeable 22 and 15 % for the yellow and red donors, respectively, across the chromophores to the blue acceptor. Metadynamics simulations suggested that the conformational properties of the antennas are driven by intramolecular chromophoric stacking interactions that, upon forcing the α-helix to fold on itself, annul any effects deriving from the programming of the spatial arrangement of the receptor sides in the peptide backbone.

On the Mechanism of Gold/NHC Compounds Binding to DNA G-Quadruplexes: Combined Metadynamics and Biophysical Methods.

The binding modes and free-energy landscape of two AuI /N-heterocyclic carbene complexes interacting with G-quadruplexes, namely a human telomeric (hTelo) and a promoter sequence (C-KIT1), are studied here for the first time by metadynamics. The theoretical results are validated by FRET DNA melting assays and provide an accurate estimate of the absolute gold complex/DNA binding free energy. This advanced in silico approach is valuable to achieve rational drug design of selective G4 binders.

Metashooting: a novel tool for free energy reconstruction from polymorphic phase transition mechanisms.

We introduce a novel scheme for the mechanistic investigation of solid-solid phase transitions, which we dub 'metashooting'. Combining transition path sampling, molecular dynamics and metadynamics, this scheme allows for both a complete mechanistic analysis and detailed mapping of the free energy surface. This is illustrated by performing metashooting calculations on the pressure-induced B4/B3 → B1 phase transition in ZnO. The resulting free energy map helps to clarify the role of intermediate configurations along this activated process and the competition between different mechanistic regimes with superior accuracy. We argue that metashooting can be efficiently applied to a broader class of activated processes.

Microscopic description of insulator-metal transition in high-pressure oxygen.

Unusual metallic states involving breakdown of the standard Fermi-liquid picture of long-lived quasiparticles in well-defined band states emerge at low temperatures near correlation-driven Mott transitions. Prominent examples are ill-understood metallic states in d- and f-band compounds near Mott-like transitions. Finding of superconductivity in solid O2 on the border of an insulator-metal transition at high pressures close to 96 GPa is thus truly remarkable. Neither the insulator-metal transition nor superconductivity are understood satisfactorily. Here, we undertake a first step in this direction by focussing on the pressure-driven insulator-metal transition using a combination of first-principles density-functional and many-body calculations. We report a striking result: the finding of an orbital-selective Mott transition in a pure p-band elemental system. We apply our theory to understand extant structural and transport data across the transition, and make a specific two-fluid prediction that is open to future test. Based thereupon, we propose a novel scenario where soft multiband modes built from microscopically coexisting itinerant and localized electronic states are natural candidates for the pairing glue in pressurized O2.

Selective orbital reconstruction in tetragonal FeS: A density functional dynamical mean-field theory study.

Transport properties of tetragonal iron monosulfide, mackinawite, show a range of complex features. Semiconductive behavior and proximity to metallic states with nodal superconductivity mark this d-band system as unconventional quantum material. Here, we use the density functional dynamical mean-field theory (DFDMFT) scheme to comprehensively explain why tetragonal FeS shows both semiconducting and metallic responses in contrast to tetragonal FeSe which is a pseudogaped metal above the superconducting transition temperature. Within local-density-approximation plus dynamical mean-field theory (LDA+DMFT) we characterize its paramagnetic insulating and metallic phases, showing the proximity of mackinawite to selective Mott localization. We report the coexistence of pseudogaped and anisotropic Dirac-like electronic dispersion at the border of the Mott transition. These findings announce a new understanding of many-particle physics in quantum materials with coexisting Dirac-fermions and pseudogaped electronic states at low energies. Based on our results we propose that in electron-doped FeS substantial changes would be seen when the metallic regime was tuned towards an electronic state that hosts unconventional superconductivity.

The mechanism of aquaporin inhibition by gold compounds elucidated by biophysical and computational methods.

The inhibition of water and glycerol permeation via human aquaglyceroporin-3 (AQP3) by gold(iii) complexes has been studied by stopped-flow spectroscopy and, for the first time, its mechanism has been described using molecular dynamics (MD), combined with density functional theory (DFT) and electrochemical studies. The obtained MD results showed that the most effective gold-based inhibitor, anchored to Cys40 in AQP3, is able to induce shrinkage of pores preventing glycerol and water permeation. Moreover, the good correlation between the affinity of the Au(iii) complex to Cys binding and AQP3 inhibition effects was highlighted, while no influence of the different oxidative character of the complexes could be observed.

Enzymatic synthesis of natural (+)-aristolochene from a non-natural substrate.

The sesquiterpene cyclase aristolochene synthase from Penicillium roquefortii (PR-AS) has evolved to catalyse with high specificity (92%) the conversion of farnesyl diphosphate (FDP) to the bicyclic hydrocarbon (+)-aristolochene, the natural precursor of several fungal toxins. Here we report that PR-AS converts the unnatural FDP isomer 7-methylene farnesyl diphosphate to (+)-aristolochene via the intermediate 7-methylene germacrene A. Within the confined space of the enzyme's active site, PR-AS stabilises the reactive conformers of germacrene A and 7-methylene germacrene A, respectively, which are protonated by the same active site acid (most likely HOPPi) to yield the shared natural bicyclic intermediate eudesmane cation, from which (+)-aristolochene is then generated.

Mechanism of Germacradien-4-ol Synthase-Controlled Water Capture.

The sesquiterpene synthase germacradiene-4-ol synthase (GdolS) from Streptomyces citricolor is one of only a few known high-fidelity terpene synthases that convert farnesyl diphosphate (FDP) into a single hydroxylated product. Crystals of unliganded GdolS-E248A diffracted to 1.50 Å and revealed a typical class 1 sesquiterpene synthase fold with the active site in an open conformation. The metal binding motifs were identified as D(80)DQFD and N(218)DVRSFAQE. Some bound water molecules were evident in the X-ray crystal structure, but none were obviously positioned to quench a putative final carbocation intermediate. Incubations in H2(18)O generated labeled product, confirming that the alcohol functionality arises from nucleophilic capture of the final carbocation by water originating from solution. Site-directed mutagenesis of amino acid residues from both within the metal binding motifs and without identified by sequence alignment with aristolochene synthase from Aspergillus terreus generated mostly functional germacradien-4-ol synthases. Only GdolS-N218Q generated radically different products (∼50% germacrene A), but no direct evidence of the mechanism of incorporation of water into the active site was obtained. Fluorinated FDP analogues 2F-FDP and 15,15,15-F3-FDP were potent noncompetitive inhibitors of GdolS. 12,13-DiF-FDP generated 12,13-(E)-ß-farnesene upon being incubated with GdolS, suggesting stepwise formation of the germacryl cation during the catalytic cycle. Incubation of GdolS with [1-(2)H2]FDP and (R)-[1-(2)H]FDP demonstrated that following germacryl cation formation a [1,3]-hydride shift generates the final carbocation prior to nucleophilic capture. The stereochemistry of this shift is not defined, and the deuteron in the final product was scrambled. Because no clear candidate residue for binding of a nucleophilic water molecule in the active site and no significant perturbation of product distribution from the replacement of active site residues were observed, the final carbocation may be captured by a water molecule from bulk solvent.

Hierarchical thermoelectrics: crystal grain boundaries as scalable phonon scatterers.

Thermoelectric materials are strategically valuable for sustainable development, as they allow for the generation of electrical energy from wasted heat. In recent years several strategies have demonstrated some efficiency in improving thermoelectric properties. Dopants affect carrier concentration, while thermal conductivity can be influenced by alloying and nanostructuring. Features at the nanoscale positively contribute to scattering phonons, however those with long mean free paths remain difficult to alter. Here we use the concept of hierarchical nano-grains to demonstrate thermal conductivity reduction in rocksalt lead chalcogenides. We demonstrate that grains can be obtained by taking advantage of the reconstructions along the phase transition path that connects the rocksalt structure to its high-pressure form. Since grain features naturally change as a function of size, they impact thermal conductivity over different length scales. To understand this effect we use a combination of advanced molecular dynamics techniques to engineer grains and to evaluate thermal conductivity in PbSe. By affecting grain morphologies only, i.e. at constant chemistry, two distinct effects emerge: the lattice thermal conductivity is significantly lowered with respect to the perfect crystal, and its temperature dependence is markedly suppressed. This is due to an increased scattering of low-frequency phonons by grain boundaries over different size scales. Along this line we propose a viable process to produce hierarchical thermoelectric materials by applying pressure via a mechanical load or a shockwave as a novel paradigm for material design.

Microwave-Assisted Synthesis of Defects Metal-Imidazolate-Amide-Imidate Frameworks and Improved CO2 Capture.

In this work, we report three isostructural 3D frameworks, named IFP-11 (R = Cl), IFP-12 (R = Br), and IFP-13 (R = Et) (IFP = Imidazolate Framework Potsdam) based on a cobalt(II) center and the chelating linker 2-substituted imidazolate-4-amide-5-imidate. These chelating ligands were generated in situ by partial hydrolysis of 2-substituted 4,5-dicyanoimidazoles under microwave (MW)-assisted conditions in DMF. Structure determination of these IFPs was investigated by IR spectroscopy and a combination of powder X-ray diffraction (PXRD) with structure modeling. The structural models were initially built up from the single-crystal X-ray structure determination of IFP-5 (a cobalt center and 2-methylimidazolate-4-amide-5-imidate linker based framework) and were optimized by using density functional theory calculations. Substitution on position 2 of the linker (R = Cl, Br, and Et) in the isostructural IFP-11, -12, and -13 allowed variation of the potential pore window in 1D hexagonal channels (3.8 to 1.7 Å). The potential of the materials to undergo specific interactions with CO2 was measured by the isosteric heat of adsorption. Further, we resynthesized zinc based IFPs, namely IFP-1 (R = Me), IFP-2 (R = Cl), IFP-3 (R = Br), and IFP-4 (R = Et), and cobalt based IFP-5 under MW-assisted conditions with higher yield. The transition from a nucleation phase to the pure crystalline material of IFP-1 in MW-assisted synthesis depends on reaction time. IFP-1, -3, and -5, which are synthesized by MW-assisted conditions, showed an enhancement of N2 and CO2, compared to the analogous conventional electrical (CE) heating method based materials due to crystal defects.

Magnetoresistance in the Spin-Orbit Kondo State of Elemental Bismuth.

Materials with strong spin-orbit coupling, which competes with other particle-particle interactions and external perturbations, offer a promising route to explore novel phases of quantum matter. Using LDA + DMFT we reveal the complex interplay between local, multi-orbital Coulomb and spin-orbit interaction in elemental bismuth. Our theory quantifies the role played by collective dynamical fluctuations in the spin-orbit Kondo state. The correlated electronic structure we derive is promising in the sense that it leads to results that might explain why moderate magnetic fields can generate Dirac valleys and directional-selective magnetoresistance responses within spin-orbit Kondo metals.

Zeolitic imidazolate framework-71 nanocrystals and a novel SOD-type polymorph: solution mediated phase transformations, phase selection via coordination modulation and a density functional theory derived energy landscape.

We report a rapid additive-free synthesis of nanocrystals (NCs) of RHO-type ZIF-71 () of composition [Zn(dcim)2] (dcim = 4,5-dichloroimidazolate) in 1-propanol as solvent at room temperature. NC- has a size of 30-60 nm and exhibits permanent microporosity with a surface area (SBET = 970 m(2) g(-1)) comparable to that of microcrystalline material. When kept under the mother solution NC- undergoes transformation into a novel SOD-type polymorph (), which in turn converts into known ZIF-72 () with lcs topology. It is shown that microcrystals (MCs) of can be favourably synthesised using 1-methylimidazole as a coordination modulator. NC- with size <200 nm was prepared using NC-ZIF-8 as a template with SOD topology in a solvent assisted ligand exchange-related process. DFT-assisted Rietveld analysis of powder XRD data revealed that novel polymorph possesses an unusual SOD framework conformation. was further characterised with regard to microporosity (SBET = 597 m(2) g(-1)) and thermal as well as chemical stability. DFT calculations were performed to search for further potentially existing but not-yet synthesised polymorphs in the [Zn(dcim)2] system.

Theoretical investigation of the electronic structure and quantum transport in the graphene-C(111) diamond surface system.

We investigate the interaction of a graphene monolayer with the C(111) diamond surface using ab initio density functional theory. To accommodate the lattice mismatch between graphene and diamond, the overlayer deforms into a wavy structure that binds strongly to the diamond substrate. The detached ridges of the wavy graphene overlayer behave electronically as free-standing polyacetylene chains with delocalized π electrons, separated by regions containing only sp(3) carbon atoms covalently bonded to the (111) diamond surface. We performed quantum transport calculations for different geometries of the system to study how the buckling of the graphene layer and the associated bonding to the diamond substrate affect the transport properties. The system displays high carrier mobility along the ridges and a wide transport gap in the direction normal to the ridges. These intriguing, strongly anisotropic transport properties qualify the hybrid graphene-diamond system as a viable candidate for electronic nanodevices.