Manuela Mura

Role of van der Waals interaction in forming molecule-metal junctions: flat organic molecules on the Au(111) surface.

The self-assembly of flat organic molecules on metal surfaces is controlled, apart from the kinetic factors, by the interplay between the molecule-molecule and molecule-surface interactions. These are typically calculated using standard density functional theory within the generalized gradient approximation, which significantly underestimates nonlocal correlations, i.e. van der Waals (vdW) contributions, and thus affects interactions between molecules and the metal surface in the junction. In this paper we address this question systematically for the Au(111) surface and a number of popular flat organic molecules which form directional hydrogen bonds with each other. This is done using the recently developed first-principles vdW-DF method which takes into account the nonlocal nature of electron correlation [M. Dion et al., Phys. Rev. Lett. 2004, 92, 246401]. We report here a systematic study of such systems involving completely self-consistent vdW-DF calculations with full geometry relaxation. We find that the hydrogen bonding between the molecules is only insignificantly affected by the vdW contribution, both in the gas phase and on the gold surface. However, the adsorption energies of these molecules on the surface increase dramatically as compared with the ordinary density functional (within the generalized gradient approximation, GGA) calculations, in agreement with available experimental data and previous calculations performed within approximate or semiempirical models, and this is entirely due to the vdW contribution which provides the main binding mechanism. We also stress the importance of self-consistency in calculating the binding energy by the vdW-DF method since the results of non-self-consistent calculations in some cases may be off by up to 20%. Our calculations still support the usually made assumption of the molecule-surface interaction changing little laterally suggesting that single molecules and their small clusters should be quite mobile at room temperature on the surface. These findings support a gas-phase modeling for some flat metal surfaces, such as Au(111), and flat molecules, at least as a first approximation.

An investigation into the interactions between self-assembled adenine molecules and a Au(111) surface

Two molecular phases of the DNA base adenine (A) on a Au(111) surface are observed by using STM under ultrahigh-vacuum conditions. One of these phases is reported for the first time. A systematic approach that considers all possible gas-phase two-dimensional arrangements of A molecules connected by double hydrogen bonds with each other and subsequent ab initio DFT calculations are used to characterize and identify the two phases. The influence of the gold surface on the structure of A assemblies is also discussed. DFT is found to predict a smooth corrugation potential of the gold surface that will enable A molecules to move freely across the surface at room temperature. This conclusion remains unchanged if van der Waals interaction between A and gold is also approximately taken into account. DFT calculations of the A pairs on the Au(111) surface show its negligible effect on the hydrogen bonding between the molecules. These results justify the gas-phase analysis of possible assemblies on flat metal surfaces. Nevertheless, the fact that it is not the most stable gas-phase monolayer that is actually observed on the gold surface indicates that the surface still plays a subtle role, which needs to be properly addressed.

Understanding the disorder of the DNA base cytosine on the Au(111) surface

Using ultrahigh vacuum scanning tunneling microscopy (STM) and ab initio density functional theory, we have investigated in detail structures formed by cytosine on the Au(111) surface in clean ultrahigh vacuum conditions. In spite of the fact that the ground state of this DNA base on the surface is shown to be an ordered arrangement of cytosine one-dimensional branches (filaments), this structure has never been observed in our STM experiments. Instead, disordered structures are observed, which can be explained by only a few elementary structural motifs: filaments, five- and sixfold rings, which randomly interconnect with each other forming bent chains, T junctions, and nanocages. The latter may have trapped smaller structures inside. The formation of such an unusual assembly is explained by simple kinetic arguments as a liquid-glass transition.

Supramolecular Porous Network Formed by Molecular Recognition between Chemically Modified Nucleobases Guanine and Cytosine

The involvement of surfaces in the origin of the first genetic molecules on Earth has long been suggested. Prior to the emergence of nucleic acid polymerases in the prebiotic soup, the self-assembly of primitive nucleobase building blocks may have relied on surface-mediated recognition events which catalyzed the formation of a covalent backbone in prototype oligonucleotides that subsequently may have functioned as templates in a primitive copying mechanism. This initial replication process may have been catalyzed by surfaces or chemical substances in solution—including RNA itself, as postulated in the RNA world hypothesis. Today, the role and the relative importance of the basic, fundamental driving forces for nucleic acid replication such as base pairing, base stacking, and steric effects are still under intense debate. Watson–Crick hydrogen bonding has traditionally been thought to be a prerequisite for high-fidelity DNA replication. However, recent studies on nucleobase analogues with the same size and shape as the natural ones but without relevant hydrogen-bonding groups have revealed that these analogues can recognize each other with high fidelity when incorporated into DNA sequences in vivo. Watson–Crick hydrogen bonding thus seems not to be a requisite for the selectivity of base pairing in DNA replication. However, in the absence of polymerases in the prebiotic soup, Watson– Crick hydrogen bonding may have played a more crucial role in the molecular recognition between the nucleobase building blocks at surfaces and for further polymerization. In support of this postulation, molecular recognition between complementary bases, most likely driven by hydrogen bonding alone, has already been observed both at the liquid/solid (HOPG) interface and on the noble Au(111) surface under extreme ultrahigh vacuum (UHV) conditions. These previous experiments were, however, conducted with nucleobases alone, and hence did not take the presence of deoxyribose into account. It is therefore of utmost importance to explore the role that Watson–Crick hydrogen bonding plays at surfaces in chemical structures that mimic nucleotides so as to address the fundamental question of how the polymerization of nucleotides may have started in the prebiotic soup in the absence of enzymes. The development of the scanning tunneling microscopy (STM) technique has advanced our understanding of supramolecular self-assembly systems on surfaces and has allowed intermolecular interactions to be explored at the submolecular scale. Herein we show by using a combination of high-resolution STM imaging and density functional theory (DFT) that sequential co-deposition of N-aryl-modified nucleobases cytosine (C) and guanine (G) onto the Au(111) surface under UHV conditions results in the formation of highly ordered supramolecular porous networks, where Watson–Crick hydrogen bonding between chemically modified C and G molecules plays the primary role in their stabilization. As the N-arylation of the nucleobases has been performed on the nitrogen atom normally attached to the sugar moiety in DNA or RNA (Scheme 1), these N-aryl-modified nucleobases thus represent two-dimensional (2D) structural mimics of naturally occurring nucleotides. The current results outline a new route for directing the self-assembly of nucleobase-derived nanostructures at the surface. Furthermore, the observed [*] Prof. W. Xu, Dr. M. F. Jacobsen, Dr. M. Yu, Prof. E. Laegsgaard, Prof. I. Stensgaard, Prof. T. R. Linderoth, Prof. J. Kjems, Prof. K. V. Gothelf, Prof. F. Besenbacher Interdisciplinary Nanoscience Center (iNANO) and Center for DNA Nanotechnology (CDNA), Department of Physics and Astronomy, Department of Chemistry, and Department of Molecular Biology, Aarhus University 8000 Aarhus C (Denmark) E-mail: fbe@inano.au.dk

Theoretical study of melamine superstructures and their interaction with the Au(111) surface

Using a systematic method, based on considering all possible hydrogen bond connections between two melamine molecules, and ab initio density functional theory (DFT) calculations, we consider the possible planar superstructures that the molecules can form in two dimensions. This is relevant to the assembly of melamine on flat metal surfaces with a small lateral corrugation of the molecule-surface interaction energy. The structures considered include small clusters as well as periodic structures, such as one-dimensional filaments and two-dimensional monolayers. Then, the interaction of melamine structures with the Au(111) surface is considered in detail to elucidate the possible effect of the surface on the formed structures, including the influence of the van der Waals interaction, which is not taken into account in DFT-based methods. The problem of commensurability between the lattices of the gas-phase monolayer and of the substrate is also discussed.

The increasing role of phosphatidylethanolamine as a lipid receptor in the action of host defence peptides

Host defence peptides (HDPs) are antimicrobial agents produced by organisms across the prokaryotic and eukaryotic kingdoms. Many prokaryotes produce HDPs, which utilise lipid and protein receptors in the membranes of bacterial competitors to facilitate their antibacterial action and thereby survive in their niche environment. As a major example, it is well established that cinnamycin and duramycins from Streptomyces have a high affinity for phosphatidylethanolamine (PE) and exhibit activity against other Gram-positive organisms, such as Bacillus. In contrast, although eukaryotic HDPs utilise membrane interactive mechanisms to facilitate their antimicrobial activity, the prevailing view has long been that these mechanisms do not involve membrane receptors. However, this view has been recently challenged by reports that a number of eukaryotic HDPs such as plant cyclotides also use PE as a receptor to promote their antimicrobial activities. Here, we review current understanding of the mechanisms that underpin the use of PE as a receptor in the antimicrobial and other biological actions of HDPs and describe medical and biotechnical uses of these peptides, which range from tumour imaging and detection to inclusion in topical microbicidal gels to prevent the sexual transmission of HIV.

Aurein 2.3 functionality is supported by oblique orientated α-helical formation.

In this study, an amphibian antimicrobial peptide, aurein 2.3, was predicted to use oblique orientated α-helix formation in its mechanism of membrane destabilisation. Molecular dynamic (MD) simulations and circular dichroism (CD) experimental data suggested that aurein 2.3 exists in solution as unstructured monomers and folds to form predominantly α-helical structures in the presence of a dimyristoylphosphatidylcholine membrane. MD showed that the peptide was highly surface active, which supported monolayer data where the peptide induced surface pressure changes>34 mNm(-1). In the presence of a lipid membrane MD simulations suggested that under hydrophobic mismatch the peptide is seen to insert via oblique orientation with a phenylalanine residue (PHE3) playing a key role in the membrane interaction. There is evidence of snorkelling leucine residues leading to further membrane disruption and supporting the high level of lysis observed using calcein release assays (76%). Simulations performed at higher peptide/lipid ratio show peptide cooperativity is key to increased efficiency leading to pore-formation.

Homochiral xanthine quintet networks self-assembled on Au(111) surfaces.

Xanthine molecule is an intermediate in nucleic acid degradation from the deamination of guanine and is also a compound present in the ancient solar system that is found in high concentrations in extraterrestrial meteorites. The self-assembly of xanthine molecules on inorganic surfaces is therefore of interest for the study of biochemical processes, and it may also be relevant to the fundamental understanding of prebiotic biosynthesis. Using a combination of high-resolution scanning tunneling microscopy (STM) and density functional theory (DFT) calculations, two new homochiral xanthine structures have been found on Au(111) under ultrahigh vacuum conditions. Xanthine molecules are found to be self-assembled into two extended homochiral networks tiled by two types of di-pentamer units and stabilized by intermolecular double hydrogen bonding. Our findings indicate that the deamination of guanine into xanthine leads to a very different base pairing potential and the chemical properties of the base which may be of relevance to the function of the cell and potential development of human diseases. Moreover, the adsorption of xanthine molecules on inorganic surfaces leading to homochiral assemblies may be of interest for the fundamental understanding of the emerged chirality at early stages of life.

The role of C-terminal amidation in the membrane interactions of the anionic antimicrobial peptide, maximin H5.

Maximin H5 is an anionic antimicrobial peptide from amphibians, which carries a C-terminal amide moiety, and was found to be moderately haemolytic (20%). The α-helicity of the peptide was 42% in the presence of lipid mimics of erythrocyte membranes and was found able to penetrate (10.8 mN m(-1)) and lyse these model membranes (64 %). In contrast, the deaminated peptide exhibited lower levels of haemolysis (12%) and α-helicity (16%) along with a reduced ability to penetrate (7.8 m Nm(-1)) and lyse (55%) lipid mimics of erythrocyte membranes. Taken with molecular dynamic simulations and theoretical analysis, these data suggest that native maximin H5 primarily exerts its haemolytic action via the formation of an oblique orientated α-helical structure and tilted membrane insertion. However, the C-terminal deamination of maximin H5 induces a loss of tilted α-helical structure, which abolishes the ability of the peptides N-terminal and C-terminal regions to H-bond and leads to a loss in haemolytic ability. Taken in combination, these observations strongly suggest that the C-terminal amide moiety carried by maximin H5 is required to stabilise the adoption of membrane interactive tilted structure by the peptide. Consistent with previous reports, these data show that the efficacy of interaction and specificity of maximin H5 for membranes can be attenuated by sequence modification and may assist in the development of variants of the peptide with the potential to serve as anti-infectives.

A novel form of bacterial resistance to the action of eukaryotic host defense peptides, the use of a lipid receptor

Host defense peptides show great potential for development as new antimicrobial agents with novel mechanisms of action. However, a small number of resistance mechanisms to their action are known, and here, we report a novel bacterial resistance mechanism mediated by a lipid receptor. Maximin H5 from Bombina maxima bound anionic and zwitterionic membranes with low affinity (Kd > 225 μM) while showing a strong ability to lyse (>55%) and penetrate (π > 6.0 mN m(-1)) these membranes. However, the peptide bound Escherichia coli and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) membranes with higher affinity (Kd < 65 μM) and showed a very low ability for bilayer lysis (<8%) and partitioning (π > 1.0 mN m(-1)). Increasing levels of membrane DMPE correlated with enhanced binding by the peptide (R(2) = 0.96) but inversely correlated with its lytic ability (R(2) = 0.98). Taken with molecular dynamic simulations, these results suggest that maximin H5 possesses membranolytic activity, primarily involving bilayer insertion of its strongly hydrophobic N-terminal region. However, this region was predicted to form multiple hydrogen bonds with phosphate and ammonium groups within PE head-groups, which in concert with charge-charge interactions anchor the peptide to the surface of E. coli membranes, inhibiting its membranolytic action.