Folding and self-assembly of the TatA translocation pore based on a charge zipper mechanism.

We propose a concept for the folding and self-assembly of the pore-forming TatA complex from the Twin-arginine translocase and of other membrane proteins based on electrostatic "charge zippers." Each subunit of TatA consists of a transmembrane segment, an amphiphilic helix (APH), and a C-terminal densely charged region (DCR). The sequence of charges in the DCR is complementary to the charge pattern on the APH, suggesting that the protein can be "zipped up" by a ladder of seven salt bridges. The length of the resulting hairpin matches the lipid bilayer thickness, hence a transmembrane pore could self-assemble via intra- and intermolecular salt bridges. The steric feasibility was rationalized by molecular dynamics simulations, and experimental evidence was obtained by monitoring the monomer-oligomer equilibrium of specific charge mutants. Similar "charge zippers" are proposed for other membrane-associated proteins, e.g., the biofilm-inducing peptide TisB, the human antimicrobial peptide dermcidin, and the pestiviral E(RNS) protein.

Tetrazole and oxadiazole derivatives as thermally activated delayed fluorescence emitters.

Organic light-emitting diodes (OLEDs) are promising lighting solutions for sustainability and energy efficiency. Incorporating thermally activated delayed fluorescence (TADF) molecules enables OLEDs to achieve internal quantum efficiency (IQE), in principle, up to 100%; therefore, new classes of promising TADF emitters and modifications of existing ones are sought after. This study explores the TADF emission properties of six designed TADF emitters, examining their photophysical responses using experimental and theoretical methods. The design strategy involves creating six distinct types of a donor-acceptor (D-A) system, where tert-butylcarbazoles are used as donors, while the acceptor component incorporates three different functional groups: nitrile, tetrazole and oxadiazole, with varying electron-withdrawing character. Additionally, the donor-acceptor distance is adjusted using a phenylene spacer, and its influence on TADF functionality is examined. The clear dependency of an additional spacer, inhibiting TADF, could be revealed. Emitters with a direct donor-acceptor connection are demonstrated to exhibit TADF moderate emissive behavior. The analysis emphasizes the impact of charge transfer, singlet-triplet energy gaps (ΔEST), and other microscopic parameters on photophysical rates, permitting TADF. Among the emitters, TCz-CN shows optimal performance as a blue-green emitter with an 88% photoluminescence quantum yield (PLQY) and fast rate of reversible intersystem crossing of 2x106 s-1.

Length matters: Functional flip of the short TatA transmembrane helix.

The twin arginine translocase (Tat) exports folded proteins across bacterial membranes. The putative pore-forming or membrane-weakening component (TatAd in B. subtilis) is anchored to the lipid bilayer via an unusually short transmembrane α-helix (TMH), with less than 16 residues. Its tilt angle in different membranes was analyzed under hydrophobic mismatch conditions, using synchrotron radiation circular dichroism and solid-state NMR. Positive mismatch (introduced either by reconstitution in short-chain lipids or by extending the hydrophobic TMH length) increased the helix tilt of the TMH as expected. Negative mismatch (introduced either by reconstitution in long-chain lipids or by shortening the TMH), on the other hand, led to protein aggregation. These data suggest that the TMH of TatA is just about long enough for stable membrane insertion. At the same time, its short length is a crucial factor for successful translocation, as demonstrated here in native membrane vesicles using an in vitro translocation assay. Furthermore, when reconstituted in model membranes with negative spontaneous curvature, the TMH was found to be aligned parallel to the membrane surface. This intrinsic ability of TatA to flip out of the membrane core thus seems to play a key role in its membrane-destabilizing effect during Tat-dependent translocation.

Molecular-Engineered Biradicals Based on the YIII-Phthalocyanine Platform.

A mixed-ligand phthalocyanine/porphyrin yttrium(III) radical double-decker complex (DD) was synthesized using the custom-made 5,10,15-tris(4-methoxyphenyl)-20-(4-((trimethylsilyl)ethynyl)phenyl)porphyrin. The trimethylsilyl functionality was then used to couple two such complexes into biradicals through rigid tethers. Glaser coupling was used to synthesize a short-tethered biradical (C1) and Sonogashira coupling to synthesize longer-tethered ones (C2 and C3). Field-swept echo-detected (FSED), saturation recovery, and spin nutation-pulsed electron paramagnetic resonance experiments revealed marked similarities of the magnetic properties of DD with those of the parent [Y(pc)2]• complex, both in the solid state and in CD2Cl2/CDCl3 4:1 frozen glasses. FSED experiments on the biradicals C2 and C3 revealed a spectral broadening with respect to the spectra of DD and [Y(pc)2]• assigned to the effect of dipolar interactions in solution. Apart from the main resonance, satellite features were also observed, which were simulated with dipole-dipole pairs of shortest distances, suggesting spin delocalization on the organic tether. FSED experiments on C1 yielded spectral line shapes that could not be simulated as the integration of the off-resonance echoes was complicated by field-dependent modulations. While, for all dimers, the on-resonance spin nutation experiments yielded Rabi oscillations of the same frequencies, off-resonance nutations on C1 yielded Rabi oscillations that could be assigned to a MS = -1 to MS = 0 transition within a S = 1 multiplet. The DFT calculations showed that the trans conformation of the complexes was significantly more stable than the cis one and that it induced a marked spin delocalization over the rigid organic tether. This "spin leakage" was most pronounced for the shortest biradical C1.

Key Role of Choline Head Groups in Large Unilamellar Phospholipid Vesicles for the Interaction with and Rupture by Silica Nanoparticles.

For highly abundant silica nanomaterials, detrimental effects on proteins and phospholipids are postulated as critical molecular initiating events that involve hydrogen-bonding, hydrophobic, and/or hydrophilic interactions. Here, large unilamellar vesicles with various well-defined phospholipid compositions are used as biomimetic models to recapitulate membranolysis, a process known to be induced by silica nanoparticles in human cells. Differential analysis of the dominant phospholipids determined in membranes of alveolar lung epithelial cells demonstrates that the quaternary ammonium head groups of phosphatidylcholine and sphingomyelin play a critical and dose-dependent role in vesicle binding and rupture by amorphous colloidal silica nanoparticles. Surface modification by either protein adsorption or by covalent coupling of carboxyl groups suppresses the disintegration of these lipid vesicles, as well as membranolysis in human A549 lung epithelial cells by the silica nanoparticles. Furthermore, molecular modeling suggests a preferential affinity of silanol groups for choline head groups, which is also modulated by the pH value. Biomimetic lipid vesicles can thus be used to better understand specific phospholipid-nanoparticle interactions at the molecular level to support the rational design of safe advanced materials.

Multiscale Model of CVD Growth of Graphene on Cu(111) Surface.

Due to its outstanding properties, graphene has emerged as one of the most promising 2D materials in a large variety of research fields. Among the available fabrication protocols, chemical vapor deposition (CVD) enables the production of high quality single-layered large area graphene. To better understand the kinetics of CVD graphene growth, multiscale modeling approaches are sought after. Although a variety of models have been developed to study the growth mechanism, prior studies are either limited to very small systems, are forced to simplify the model to eliminate the fast process, or they simplify reactions. While it is possible to rationalize these approximations, it is important to note that they have non-trivial consequences on the overall growth of graphene. Therefore, a comprehensive understanding of the kinetics of graphene growth in CVD remains a challenge. Here, we introduce a kinetic Monte Carlo protocol that permits, for the first time, the representation of relevant reactions on the atomic scale, without additional approximations, while still reaching very long time and length scales of the simulation of graphene growth. The quantum-mechanics-based multiscale model, which links kinetic Monte Carlo growth processes with the rates of occurring chemical reactions, calculated from first principles makes it possible to investigate the contributions of the most important species in graphene growth. It permits the proper investigation of the role of carbon and its dimer in the growth process, thus indicating the carbon dimer to be the dominant species. The consideration of hydrogenation and dehydrogenation reactions enables us to correlate the quality of the material grown within the CVD control parameters and to demonstrate an important role of these reactions in the quality of the grown graphene in terms of its surface roughness, hydrogenation sites, and vacancy defects. The model developed is capable of providing additional insights to control the graphene growth mechanism on Cu(111), which may guide further experimental and theoretical developments.

Twisting of Porphyrin by Assembly in a Metal-Organic Framework yielding Chiral Photoconducting Films for Circularly-Polarized-Light Detection.

While materials based on organic molecules usually have either superior optoelectronic or superior chiral properties, the combination of both is scarce. Here, a crystalline chiroptical film based on porphyrin with homochiral side groups is presented. While the dissolved molecule has a planar, thus, achiral porphyrin core, upon assembly in a metal-organic framework (MOF) film, the porphyrin core is twisted and chiral. The close packing and the crystalline order of the porphyrin cores in the MOF film also results in excellent optoelectronic properties. By exciting the Soret band of porphyrin, efficient photoconduction with a high On-Off-ratio is realized. More important, handedness-dependent circularly-polarized-light photoconduction with a dissymmetry factor g of 4.3×10-4 is obtained. We foresee the combination of such assembly-induced chirality with the rich porphyrin chemistry will enable a plethora of organic materials with exceptional chiral and optoelectronic properties.

Anion Storage Chemistry of Organic Cathodes for High-Energy and High-Power Density Divalent Metal Batteries.

Multivalent batteries show promising prospects for next-generation sustainable energy storage applications. Herein, we report a polytriphenylamine (PTPAn) composite cathode capable of highly reversible storage of tetrakis(hexafluoroisopropyloxy) borate [B(hfip)4 ] anions in both Magnesium (Mg) and calcium (Ca) battery systems. Spectroscopic and computational studies reveal the redox reaction mechanism of the PTPAn cathode material. The Mg and Ca cells exhibit a cell voltage >3 V, a high-power density of ∼∼3000 W kg-1 and a high-energy density of ∼∼300 Wh kg-1 , respectively. Moreover, the combination of the PTPAn cathode with a calcium-tin (Ca-Sn) alloy anode could enable a long battery-life of 3000 cycles with a capacity retention of 60 %. The anion storage chemistry associated with dual-ion electrochemical concept demonstrates a new feasible pathway towards high-performance divalent ion batteries.

Controlling the Mobility of Ionic Liquids in the Nanopores of MOFs by Adjusting the Pore Size: From Conduction Collapse by Mutual Pore Blocking to Unhindered Ion Transport.

Ionic liquids (ILs) in nanoporous confinement are the core of many supercapacitors and batteries, where the mobility of the nanoconfined ILs is crucial. Here, by combining experiments based on impedance spectroscopy with molecular dynamics simulations, the mobility of a prototype IL in the nanopores of an isoreticular metal-organic framework (MOF)-series with different pore sizes is explored, where an external electric field is applied. It has been found that the conduction behavior changes tremendously depend on the pore size. For small-pore apertures, the IL cations and anions cannot pass the pore window simultaneously, causing the ions to mutually block the pores. This results in a strong concentration dependence of the ionic conduction, where the conduction drops by two orders of magnitude when filling the pores. For large-pore MOFs, the mutual hindrance of the ions in the pores is small, causing only a small concentration dependence. The cutoff between the large-pore and small-pore behavior is approximately the size of a cation-anion-dimer and increasing the pore diameter by only 0.2 nm changes the conduction behavior fundamentally. This study shows that the pore aperture size has a substantial effect on the mobility of ions in nanoporous confinement and has to be carefully optimized for realizing highly-mobile nanoconfined ILs.

Local Electronic Charge Transfer in the Helical Induction of Cis-Transoid Poly(4-carboxyphenyl)acetylene by Chiral Amines.

Understanding the phenomena that lead to the formation of a specific helicity in helical polymers remains a challenge even today. Various polymers have been shown to assume different helical screw-senses depending on different stimuli. Acid-base chiral amines, for example, can induce helical conformations on cis-transoid poly(4-carboxyphenyl)acetylene yielding high-intensity circular dichroism signals. There have been many experimental attempts to elucidate the driving forces involved, but the induction process remains unclear. Here, we investigate the mechanism of helical polymer formation by both Molecular Dynamics (MD) and Density Functional Theory (DFT) approaches. We find that DFT calculations and the dissociation energies between 4 monomer polymers and amines show a clear trend in the affinity of R and S conformers with clockwise and counterclockwise polymer screw-senses, respectively. The charge analysis revealed that the local charge transfer effect plays a crucial role that leads to the helical polymer-amine induction.

Understanding excited state properties of host materials in OLEDs: simulation of absorption spectrum of amorphous 4,4-bis(carbazol-9-yl)-2,2-biphenyl (CBP).

4,4-Bis(carbazol-9-yl)-2,2-biphenyl (CBP) is widely used as a host material in phosphorescent organic light-emitting diodes (PhOLEDs). In the present study, we simulate the absorption spectra of CBP in gas and condensed phases, respectively, using the efficient time-dependent long-range corrected tight-binding density functional theory (TD-LC-DFTB). The accuracy of the condensed-phase absorption spectra computed using the structures obtained from classical molecular dynamics (MD) and quantum mechanical/molecular mechanical (QM/MM) simulations is examined by comparison with the experimental absorption spectrum. It is found that the TD-LC-DFTB gas-phase spectrum is in good agreement with the GW-BSE spectrum, indicating TD-LC-DFTB is an accurate and robust method in calculating the excitation energies of CBP. For the condensed-phase spectrum, we find that the electrostatic embedding has a minor influence on the excitation energy. Computing accurate absorption spectra is a particular challenge since static and dynamic disorders have to be taken into account. The static disorder results from the molecular packing in the material, which leads to molecule deformations. Since these structural changes sensitively impact the excitation energies of the individual molecules, a proper representation of this static disorder indicates that a reasonable structural model of the material has been generated. The good agreement between computed and experimental absorption spectra is therefore an indicator for the structural model developed. Concerning dynamic disorder, we find that molecular changes occur on long timescales in the ns-regime, which requires the use of fast computation approaches to reach convergence. The structural models derived in this work are the basis for future studies of charge and exciton transfer in CBP and related materials, also concerning the degradation mechanisms of CBP-based PhOLEDs.

Hierarchical Coarse-Grained Strategy for Macromolecular Self-Assembly: Application to Hepatitis B Virus-Like Particles.

Macromolecular self-assembly is at the basis of many phenomena in material and life sciences that find diverse applications in technology. One example is the formation of virus-like particles (VLPs) that act as stable empty capsids used for drug delivery or vaccine fabrication. Similarly to the capsid of a virus, VLPs are protein assemblies, but their structural formation, stability, and properties are not fully understood, especially as a function of the protein modifications. In this work, we present a data-driven modeling approach for capturing macromolecular self-assembly on scales beyond traditional molecular dynamics (MD), while preserving the chemical specificity. Each macromolecule is abstracted as an anisotropic object and high-dimensional models are formulated to describe interactions between molecules and with the solvent. For this, data-driven protein-protein interaction potentials are derived using a Kriging-based strategy, built on high-throughput MD simulations. Semi-automatic supervised learning is employed in a high performance computing environment and the resulting specialized force-fields enable a significant speed-up to the micrometer and millisecond scale, while maintaining high intermolecular detail. The reported generic framework is applied for the first time to capture the formation of hepatitis B VLPs from the smallest building unit, i.e., the dimer of the core protein HBcAg. Assembly pathways and kinetics are analyzed and compared to the available experimental observations. We demonstrate that VLP self-assembly phenomena and dependencies are now possible to be simulated. The method developed can be used for the parameterization of other macromolecules, enabling a molecular understanding of processes impossible to be attained with other theoretical models.

MOF-Hosted Enzymes for Continuous Flow Catalysis in Aqueous and Organic Solvents.

Fully exploiting the potential of enzymes in cell-free biocatalysis requires stabilization of the catalytically active proteins and their integration into efficient reactor systems. Although in recent years initial steps towards the immobilization of such biomolecules in metal-organic frameworks (MOFs) have been taken, these demonstrations have been limited to batch experiments and to aqueous conditions. Here we demonstrate a MOF-based continuous flow enzyme reactor system, with high productivity and stability, which is also suitable for organic solvents. Under aqueous conditions, the stability of the enzyme was increased 30-fold, and the space-time yield exceeded that obtained with other enzyme immobilization strategies by an order of magnitude. Importantly, the infiltration of the proteins into the MOF did not require additional functionalization, thus allowing for time- and cost-efficient fabrication of the biocatalysts using label-free enzymes.

DNA Binding to the Silica: Cooperative Adsorption in Action.

The adsorption and desorption of nucleic acid to a solid surface is ubiquitous in various research areas like pharmaceutics, nanotechnology, molecular biology, and molecular electronics. In spite of this widespread importance, it is still not well understood how the negatively charged deoxyribonucleic acid (DNA) binds to the negatively charged silica surface in an aqueous solution. In this article, we study the adsorption of DNA to the silica surface using both modeling and experiments and shed light on the complicated binding (DNA to silica) process. The binding agent mediated DNA adsorption was elegantly captured by cooperative Langmuir model. Bulk-depletion experiments were performed to conclude the necessity of a positively charged binding agent for efficient DNA binding, which complements the findings from the model. A profound understanding of DNA binding will help to tune various processes for efficient nucleic acid extraction and purification. However, this work goes beyond the DNA binding and can shed light on other binding agent mediated surface-surface, surface-molecule, molecule-molecule interaction.

A coarse-grained xDLVO model for colloidal protein-protein interactions.

Colloidal protein-protein interactions (PPIs) of attractive and repulsive nature modulate the solubility of proteins, their aggregation, precipitation and crystallization. Such interactions are very important for many biotechnological processes, but are complex and hard to control, therefore, difficult to be understood in terms of measurements alone. In diluted protein solutions, PPIs can be estimated from the osmotic second virial coefficient, B22, which has been calculated using different methods and levels of theory. The most popular approach is based on the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory and its extended versions, i.e. xDLVO. Despite much efforts, these models are not fully quantitative and must be fitted to experiments, which limits their predictive value. Here, we report an extended xDLVO-CG model, which extends existing models by a coarse-grained representation of proteins and the inclusion of an additional ion-protein dispersion interaction term. We demonstrate for four proteins, i.e. lysozyme (LYZ), subtilisin (Subs), bovine serum albumin (BSA) and immunoglobulin (IgG1), that semi-quantitative agreement with experimental values without the need to fit to experimental B22 values. While most likely not the final step in the nearly hundred years of research in PPIs, xDLVO-CG is a step towards predictive PPIs calculations that are transferable to different proteins.

The effects of somatic mutations on EGFR interaction with anti-EGFR monoclonal antibodies: Implication for acquired resistance.

A number of mutations in the epidermal growth factor receptor (EGFR) have been identified that imparts resistance to anti-EGFR monoclonal antibodies (mAbs) in clinical and preclinical samples. Primary or acquired resistance to targeted therapy will eventually limit the clinical benefit of anticancer mAbs. The aim of the current study was to perform computational analysis to investigate the structural implications of the EGFR somatic mutations on its complexes with the four anti-EGFR mAbs (Cetuximab, Panitumumab, Necitumumab, and Matuzumab). Docking analysis and molecular dynamics (MD) simulations were performed to understand the plausible structural and dynamical implications caused by somatic mutations available in the Catalogue of Somatic Mutations in Cancer database on the EGFR and anti-EGFR mAbs. We found that EGFRS492R and EGFRV441I in complex with Cetuximab, EGFRR377S and EGFRS447Y in complex with Panitumumab, and EGFRV441I in complex with Necitumumab have a weakest binding affinity in comparison to EGFRWT in complex with the relevant mAb. Taken together with the results obtained from docking analysis and MD simulations, the present findings may suggest that, the S492R and V441I mutations confer resistance to Cetuximab, R377S and S447Y mutations mediate resistance to Panitumumab and finally, V441I mutation also confers resistance to Necitumumab.

Tuning Optical Properties by Controlled Aggregation: Electroluminescence Assisted by Thermally-Activated Delayed Fluorescence from Thin Films of Crystalline Chromophores.

Several photophysical properties of chromophores depend crucially on intermolecular interactions. Thermally-activated delayed fluorescence (TADF) is often influenced by close packing of the chromophore assembly. In this context, the metal-organic framework (MOF) approach has several advantages: it can be used to steer aggregation such that the orientation within aggregated structures can be predicted using rational approaches. We demonstrate this design concept for a DPA-TPE (diphenylamine-tetraphenylethylene) chromophore, which is non-emissive in its solvated state due to vibrational quenching. Turning this DPA-TPE into a ditopic linker makes it possible to grow oriented MOF thin films exhibiting pronounced green electroluminescence with low onset voltages. Measurements at different temperatures clearly demonstrate the presence of TADF. Finally, this work reports that the layer-by-layer process used for MOF thin film deposition allows the integration of the TADF-DPA-TPE in a functioning LED device.

Buffer Influence on the Amino Acid Silica Interaction.

Protein-surface interactions are exploited in various processes in life sciences and biotechnology. Many of such processes are performed in presence of a buffer system, which is generally believed to have an influence on the protein-surface interaction but is rarely investigated systematically. Combining experimental and theoretical methodologies, we herein demonstrate the strong influence of the buffer type on protein-surface interactions. Using state of the art chromatographic experiments, we measure the interaction between individual amino acids and silica, as a reference to understand protein-surface interactions. Among all the 20 proteinogenic amino acids studied, we found that arginine (R) and lysine (K) bind most strongly to silica, a finding validated by free energy calculations. We further measured the binding of R and K at different pH in presence of two different buffers, MOPS (3-(N-morpholino)propanesulfonic acid) and TRIS (tris(hydroxymethyl)aminomethane), and find dramatically different behavior. In presence of TRIS, the binding affinity of R/K increases with pH, whereas we observe an opposite trend for MOPS. These results can be understood using a multiscale modelling framework combining molecular dynamics simulation and Langmuir adsorption model. The modelling approach helps to optimize buffer conditions in various fields like biosensors, drug delivery or bio separation engineering prior to the experiment.

Disorder-driven doping activation in organic semiconductors.

Conductivity doping of organic semiconductors is an essential prerequisite for many organic devices, but the specifics of dopant activation are still not well understood. Using many-body simulations that include Coulomb interactions and dopant ionization/de-ionization events explicitly we here show significant doping efficiency even before the electron affinity of the dopant exceeds the ionization potential of the organic matrix (p-doping), similar to organic salts. We explicitly demonstrate that the ionization of weak molecular dopants in organic semiconductors is a disorder-, rather than thermally induced process. Practical implications of this finding are a weak dependence of the ionized dopant fraction on the electron affinity of the dopant, and an enhanced ionization of the weak dopants upon increasing dopant molar fraction. As a result, strategies towards dopant optimization should aim for presently neglected goals, such as the binding energy in host-dopant charge-transfer states being responsible for the number of mobile charge carriers. Insights into reported effects are provided from the analysis of the density of states, where two novel features appear upon partial dopant ionization. The findings in this work can be used in the rational design of dopant molecules and devices.

Bunching and Immobilization of Ionic Liquids in Nanoporous Metal-Organic Framework.

Room-temperature ionic liquids (ILs) are a unique, novel class of designer solvents and materials with exclusive properties, attracting substantial attention in fields like energy storage and supercapacitors as well as in ion-based signal processing and electronics. For most applications, ILs need to be incorporated or embedded in solid materials like porous hosts. We investigate the dynamic structure of ILs embedded in well-defined pores of metal-organic frameworks (MOFs). The experimental data combined with molecular dynamics simulations unveil astonishing dynamic properties of the IL in the MOF nanoconfinement. At low IL loadings, the ions drift in the pores along the electric field, whereas at high IL loadings, collective field-induced interactions of the cations and anions lead to blocking the transport, thus suppressing the ionic mobility and tremendously decreasing the conductivity. The mutual pore blockage causes immobilized ions in the pores, resulting in a highly inhomogeneous IL density and bunched-up ions at the clogged pores. These results provide novel molecular-level insights into the dynamics of ILs in nanoconfinement, significantly enhancing the tunability of IL material properties.