On-Surface Synthesis of Helicene Oligomers.

We report on-surface synthesis of heterochiral 1D heptahelicene oligomers after deposition of a racemic heptahelicene monomer on an Au(111) surface followed by Ullmann coupling under ultrahigh vacuum conditions. Structure, chirality and mode of adsorption of the resulting dimers to octamers are inferred from the scanning probe microscopy and theoretical calculations.

Structural Expansion of Cyclohepta[def]fluorene towards Azulene-Embedded Non-Benzenoid Nanographenes.

Non-benzenoid non-alternant nanographenes (NGs) have attracted increasing attention on account of their distinct electronic and structural features in comparison to their isomeric benzenoid counterparts. In this work, we present a series of unprecedented azulene-embedded NGs on Au(111) during the attempted synthesis of cyclohepta[def]fluorene-based high-spin non-Kekulé structure. Comprehensive scanning tunneling microscopy (STM) and non-contact atomic force microscopy (nc-AFM) evidence the structures and conformations of these unexpected products. The dynamics of the precursor bearing 9-(2,6-dimethylphenyl)anthracene and dihydro-dibenzo-cyclohepta[def]fluorene units and its reaction products on the surface are analyzed by density functional theory (DFT) and molecular dynamics (MD) simulations. Our study sheds light on the fundamental understanding of precursor design for the fabrication of π-extended non-benzenoid NGs on a metal surface.

Unveiling the Collaborative Effect at the Cucurbit[8]uril-MoS2 Hybrid Interface for Electrochemical Melatonin Determination.

Host-guest interactions are of paramount importance in supramolecular chemistry and in a wide range of applications. Particularly well known is the ability of cucurbit[n]urils (CB[n]) to selectively host small molecules. We show that the charge transfer and complexation capabilities of CB[n] are retained on the surface of 2D transition metal dichalcogenides (TMDs), allowing the development of efficient electrochemical sensing platforms. We unveil the mechanisms of host-guest recognition between the MoS2 -CB[8] hybrid interface and melatonin (MLT), an important molecular regulator of vital constants in vertebrates. We find that CB[8] on MoS2 organizes the receptor portals perpendicularly to the surface, facilitating MLT complexation. This advantageous adsorption geometry is specific to TMDs and favours MLT electro-oxidation, as opposed to other 2D platforms like graphene, where one receptor portal is closed. This study rationalises the cooperative interaction in 2D hybrid systems to improve the efficiency and selectivity of electrochemical sensing platforms.

Unveiling the Collaborative Effect at the Cucurbit [8] uril-MoS2 Hybrid Interface for Electrochemical Melatonin Determination.

Invited for the cover of this issue are two collaborating groups: one at the Universidad Autónoma de Madrid and the other at the Instituto de Ciencia de Materiales de Madrid. The image depicts Cucurbit[8]uril adsorbed on a transition metal dichalcogenide surface letting the cavity open for complex formation with melatonin and allowing efficient electrochemical sensing. Read the full text of the article at 10.1002/chem.202203244.

Enhancement of electronic effects at a biomolecule-inorganic interface by multivalent interactions.

The binding of peptides and proteins through multiple weak interactions is ubiquitous in nature. Biopanning has been used to "hijack" this multivalent binding for the functionalization of surfaces. For practical applications it is important to understand how multivalency influences the binding interactions and the resulting behaviour of the surface. Considering the importance of optimization of the electronic properties of surfaces in diverse electronic and optoelectronic applications, we study here the relation between the multivalency effect and the resulting modulation of the surface work function. We use 12-mer peptides, which were found to strongly bind to oxide surfaces, to functionalize indium tin oxide (ITO) surfaces. We show that the affinity of the peptides for the ITO surface, and concurrently the effect on the ITO work function, are linearly affected by the number of basic residues in the sequence. The multivalent binding interactions lead to a peptide crowding effect, and a stronger modulation of the work function for adodecapeptide than for a single basic amino acid functionalization. The bioderived molecular platform presented herein can pave the way to a novel approach to improve the performance of optoelectronic devices in an eco-friendly manner.

Unusual Scaffold Rearrangement in Polyaromatic Hydrocarbons Driven by Concerted Action of Single Gold Atoms on a Gold Surface.

Chemical transformation of polyaromatic hydrocarbon (PAH) molecules following different reaction strategies has always been the focus of organic synthesis. In this work, we report the synthesis of a PAH molecule, formation of which consists of an unusual C-C bond cleavage accompanied by a complex π-conjugated molecular scaffold rearrangement. We demonstrate that the complex chemical transformation is steered by concerted motion of individual Au0 gold atoms on a supporting Au(111) surface. This observation underpins the importance of single-atom catalysis mediated by adatoms in on-surface synthesis as well as catalytic activity of single Au0 atoms facilitating cleavage of covalent carbon bonds.

Exploiting Cooperative Catalysis for the On-Surface Synthesis of Linear Heteroaromatic Polymers via Selective C-H Activation.

Regiospecific C-H activation is a promising approach to achieve extended polymers with tailored structures. While a recent on-surface synthetic approach has enabled regioselective homocoupling of heteroaromatic molecules, only small oligomers have been achieved. Herein, selective C-H activation for dehydrogenative C-C couplings of hexaazatriphenylene by Scholl reaction is reported for the first time. By combining low-temperature scanning tunneling microscopy (STM) and atomic force microscopy (AFM), we revealed the formation of one-dimensional polymers with a double-chain structure. The details of the growth process are rationalized by density functional theory (DFT) calculations, pointing out a cooperative catalytic action of Na and Ag adatoms in steering the C-H selectivity for the polymerization.

On-Surface Strain-Driven Synthesis of Nonalternant Non-Benzenoid Aromatic Compounds Containing Four- to Eight-Membered Rings.

The synthesis of polycyclic aromatic hydrocarbons containing various non-benzenoid rings remains a big challenge facing contemporary organic chemistry despite a considerable effort made over the last decades. Herein, we present a novel route, employing on-surface chemistry, to synthesize nonalternant polycyclic aromatic hydrocarbons containing up to four distinct kinds of non-benzenoid rings. We show that the surface-induced mechanical constraints imposed on strained helical reactants play a decisive role leading to the formation of products, energetically unfavorable in solution, with a peculiar ring current stabilizing the aromatic character of the π-conjugated system. Determination of the chemical and electronic structures of the most frequent product reveals its closed-shell character and low band gap. The present study renders a new route for the synthesis of novel nonalternant polycyclic aromatic hydrocarbons or other hydrocarbons driven by internal stress imposed by the surface not available by traditional approaches of organic chemistry in solution.

Transition from Homochiral Clusters to Racemate Monolayers during 2D Crystallization of Trioxa[11]helicene on Ag(100).

The phenomenon of chiral crystallization into homochiral crystals is known for more than 170 years, yet it is still poorly understood. Studying crystallization on surfaces under well-defined condition seems a promising approach towards better understanding the intermolecular chiral recognition mechanisms during nucleation and growth. The two-dimensional aggregation of racemic trioxaundecahelicene on the single crystalline silver(100) surface has been investigated with scanning tunneling microscopy and with non-contact atomic force microscopy, as well as molecular modeling simulations. A transition from homochiral cluster motifs to heterochiral assembly into large islands with increasing coverage is observed. Force field modelling confirms higher stability of heterochiral arrangements from twelve molecules on. Results are discussed with respect to previous findings for the all-carbon heptahelicene on the same surface.

Strain-Induced Isomerization in One-Dimensional Metal-Organic Chains.

The ability to use mechanical strain to steer chemical reactions creates completely new opportunities for solution- and solid-phase synthesis of functional molecules and materials. However, this strategy is not readily applied in the bottom-up on-surface synthesis of well-defined nanostructures. We report an internal strain-induced skeletal rearrangement of one-dimensional (1D) metal-organic chains (MOCs) via a concurrent atom shift and bond cleavage on Cu(111) at room temperature. The process involves Cu-catalyzed debromination of organic monomers to generate 1,5-dimethylnaphthalene diradicals that coordinate to Cu adatoms, forming MOCs with both homochiral and heterochiral naphthalene backbone arrangements. Bond-resolved non-contact atomic force microscopy imaging combined with density functional theory calculations showed that the relief of substrate-induced internal strain drives the skeletal rearrangement of MOCs via 1,3-H shifts and shift of Cu adatoms that enable migration of the monomer backbone toward an energetically favorable registry with the Cu(111) substrate. Our findings on this strain-induced structural rearrangement in 1D systems will enrich the toolbox for on-surface synthesis of novel functional materials and quantum nanostructures.

MEPSA: minimum energy pathway analysis for energy landscapes.

UNLABELLED: From conformational studies to atomistic descriptions of enzymatic reactions, potential and free energy landscapes can be used to describe biomolecular systems in detail. However, extracting the relevant data of complex 3D energy surfaces can sometimes be laborious. In this article, we present MEPSA (Minimum Energy Path Surface Analysis), a cross-platform user friendly tool for the analysis of energy landscapes from a transition state theory perspective. Some of its most relevant features are: identification of all the barriers and minima of the landscape at once, description of maxima edge profiles, detection of the lowest energy path connecting two minima and generation of transition state theory diagrams along these paths. In addition to a built-in plotting system, MEPSA can save most of the generated data into easily parseable text files, allowing more versatile uses of MEPSA's output such as the generation of molecular dynamics restraints from a calculated path. AVAILABILITY AND IMPLEMENTATION: MEPSA is freely available (under GPLv3 license) at: http://bioweb.cbm.uam.es/software/MEPSA/ CONTACT: pagomez@cbm.csic.es. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Single-Molecule Identification of the Isomers of a Lipidic Antibody Activator.

Molecular structural elucidation can be accomplished by different techniques, such as nuclear magnetic resonance or X-ray diffraction. However, the former does not give information about the three-dimensional atomic arrangement, and the latter needs crystallizable solid samples. An alternative is direct, real-space visualization of the molecules by cryogenic scanning tunneling microscopy (STM). This technique is usually limited to thermally robust molecules because an annealing step is required for sample deposition. A landmark development has been the coupling of STM with electrospray deposition (ESD), which smooths the process and widens the scope of the visualization technique. In this work, we present the on-surface characterization of air-, light-, and temperature-sensitive rhamnopolyene with relevance in molecular biology. Supported by theoretical calculations, we characterize two isomers of this flexible molecule, confirming the potential of the technique to inspect labile, non-crystallizable compounds.

Simulation of catalytic water activation in mitochondrial F1-ATPase using a hybrid quantum mechanics/molecular mechanics approach: an alternative role for ß-Glu 188.

The use of quantum mechanics/molecular mechanics simulations to study the free energy landscape of the water activation at the catalytic site of mitochondrial F(1)-ATPase affords us insight into the generation of the nucleophile OH(-) prior to ATP hydrolysis. As a result, the ATP molecule was found to be the final proton acceptor. In the simulated pathway, the transfer of a proton to the nucleotide was not direct but occurred via a second water molecule in a manner similar to the Grotthuss mechanism proposed for proton diffusion. Residue ß-Glu 188, previously described as the putative catalytic base, was found to be involved in the stabilization of a transient hydronium ion during water activation. Simulations in the absence of the carboxylate moiety of ß-Glu 188 support this role.

Charge Engineering of the Nucleic Acid Binding Cleft of a Thermostable HIV-1 Reverse Transcriptase Reveals Key Interactions and a Novel Mechanism of RNase H Inactivation.

Coupled with PCR, reverse transcriptases (RTs) have been widely used for RNA detection and gene expression analysis. Increased thermostability and nucleic acid binding affinity are desirable RT properties to improve yields and sensitivity of these applications. The effects of amino acid substitutions in the RT RNase H domain were tested in an engineered HIV-1 group O RT, containing mutations K358R/A359G/S360A and devoid of RNase H activity due to the presence of E478Q (O3MQ RT). Twenty mutant RTs with Lys or Arg at positions interacting with the template-primer (i.e., at positions 473-477, 499-502 and 505) were obtained and characterized. Most of them produced significant amounts of cDNA at 37, 50 and 65 °C, as determined in RT-PCR reactions. However, a big loss of activity was observed with mutants A477K/R, S499K/R, V502K/R and Y505K/R, particularly at 65 °C. Binding affinity experiments confirmed that residues 477, 502 and 505 were less tolerant to mutations. Amino acid substitutions Q500K and Q500R produced a slight increase of cDNA synthesis efficiency at 50 and 65 °C, without altering the KD for model DNA/DNA and RNA/DNA heteroduplexes. Interestingly, molecular dynamics simulations predicted that those mutations inactivate the RNase H activity by altering the geometry of the catalytic site. Proof of this unexpected effect was obtained after introducing Q500K or Q500R in the wild-type HIV-1BH10 RT and mutant K358R/A359G/S360A RT. Our results reveal a novel mechanism of RNase H inactivation that preserves RT DNA binding and polymerization efficiency without substituting RNase H active site residues.

Driving a Third Generation Molecular Motor with Electrons Across a Surface.

Excitation of single molecules with electrons tunneling between a sharp metallic tip of a scanning tunneling microscope and a metal surface is one way to study and control dynamics of molecules on surfaces. Electron tunneling induced dynamics may lead to hopping, rotation, molecular switching, or chemical reactions. Molecular motors that convert rotation of subgroups into lateral movement on a surface can in principle also be driven by tunneling electrons. For such surface-bound motor molecules the efficiency of motor action with respect to electron dose is still not known. Here, the response of a molecular motor containing two rotor units in the form of overcrowded alkene groups to inelastic electron tunneling has been examined on a Cu(111) surface in ultrahigh vacuum at 5 K. Upon vibrational excitation, switching between different molecular conformations is observed, including conversion of enantiomeric states of chiral conformations. Tunneling at energies in the range of electronic excitations causes activation of motor action and movement across the surface. The expected unidirectional rotation of the two rotor units causes forward movements but with a low degree of translational directionality.

Molecular sensitised probe for amino acid recognition within peptide sequences.

The combination of low-temperature scanning tunnelling microscopy with a mass-selective electro-spray ion-beam deposition established the investigation of large biomolecules at nanometer and sub-nanometer scale. Due to complex architecture and conformational freedom, however, the chemical identification of building blocks of these biopolymers often relies on the presence of markers, extensive simulations, or is not possible at all. Here, we present a molecular probe-sensitisation approach addressing the identification of a specific amino acid within different peptides. A selective intermolecular interaction between the sensitiser attached at the tip-apex and the target amino acid on the surface induces an enhanced tunnelling conductance of one specific spectral feature, which can be mapped in spectroscopic imaging. Density functional theory calculations suggest a mechanism that relies on conformational changes of the sensitiser that are accompanied by local charge redistributions in the tunnelling junction, which, in turn, lower the tunnelling barrier at that specific part of the peptide.

Sub-angstrom noninvasive imaging of atomic arrangement in 2D hybrid perovskites.

Noninvasive imaging of the atomic arrangement in two-dimensional (2D) Ruddlesden-Popper hybrid perovskites (RPPs) is challenging because of the insulating nature and softness of the organic layers. Here, we demonstrate a sub-angstrom resolution imaging of both soft organic layers and inorganic framework in a prototypical 2D lead-halide RPP crystal via combined tip-functionalized scanning tunneling microscopy (STM) and noncontact atomic force microscopy (ncAFM) corroborated by theoretical simulations. STM measurements unveil the atomic reconstruction of the inorganic lead-halide lattice and overall twin-domain composition of the RPP crystal, while ncAFM measurements with a CO-tip enable nonperturbative visualization of the cooperative reordering of surface organic cations driven by their hydrogen bonding interactions with the inorganic lattice. Moreover, such a joint technique also allows for the atomic-scale imaging of the electrostatic potential variation across the twin-domain walls, revealing alternating quasi-1D electron and hole channels at neighboring twin boundaries, which may influence in-plane exciton transport and dissociation.

Atomic Scale Control and Visualization of Topological Quantum Phase Transition in π-Conjugated Polymers Driven by Their Length.

Quantum phase transitions (QPTs) driven by quantum fluctuations are transitions between distinct quantum phases of matter. At present, they are poorly understood and not readily controlled. Here, scanning tunneling microscopy (STM) and noncontact atomic force microscopy (nc-AFM) are used to explore atomic scale control over quantum phase transitions between two different topological quantum states of a well-defined π-conjugated polymer. The phase transition is driven by a pseudo Jahn-Teller effect that is activated above a certain polymer chain length. In addition, theoretical calculations indicate the presence of long-lasting coherent fluctuations between the polymer's two quantum phases near the phase transition, at finite temperature. This work thus presents a new way of exploring atomic-scale control over QPTs and indicates that emerging quantum criticality in the vicinity of a QPT can give rise to new states of organic matter.

Significance Of Nuclear Quantum Effects In Hydrogen Bonded Molecular Chains.

In hydrogen-bonded systems, nuclear quantum effects such as zero-point motion and tunneling can significantly affect their material properties through underlying physical and chemical processes. Presently, direct observation of the influence of nuclear quantum effects on the strength of hydrogen bonds with resulting structural and electronic implications remains elusive, leaving opportunities for deeper understanding to harness their fascinating properties. We studied hydrogen-bonded one-dimensional quinonediimine molecular networks which may adopt two isomeric electronic configurations via proton transfer. Herein, we demonstrate that concerted proton transfer promotes a delocalization of π-electrons along the molecular chain, which enhances the cohesive energy between molecular units, increasing the mechanical stability of the chain and giving rise to distinctive electronic in-gap states localized at the ends. These findings demonstrate the identification of a class of isomeric hydrogen-bonded molecular systems where nuclear quantum effects play a dominant role in establishing their chemical and physical properties. This identification is a step toward the control of mechanical and electronic properties of low-dimensional molecular materials via concerted proton tunneling.

Tailoring π-conjugation and vibrational modes to steer on-surface synthesis of pentalene-bridged ladder polymers.

The development of synthetic strategies to engineer π-conjugated polymers is of paramount importance in modern chemistry and materials science. Here we introduce a synthetic protocol based on the search for specific vibrational modes through an appropriate tailoring of the π-conjugation of the precursors, in order to increase the attempt frequency of a chemical reaction. First, we design a 1D π-conjugated polymer on Au(111), which is based on bisanthene monomers linked by cumulene bridges that tune specific vibrational modes. In a second step, upon further annealing, such vibrational modes steer the twofold cyclization reaction between adjacent bisanthene moieties, which gives rise to a long pentalene-bridged conjugated ladder polymer featuring a low bandgap. In addition, high resolution atomic force microscopy allows us to identify by atomistic insights the resonance form of the polymer, thus confirming the validity of the Glidewell and Lloyd´s rules for aromaticity. This on-surface synthetic strategy may stimulate exploiting previously precluded reactions towards π-conjugated polymers with specific structures and properties.