Charge Transfer Mechanism in Guanine-Based Self-Assembled Monolayers on a Gold Surface.

In this work, we have theoretically determined the one-electron oxidation potentials and charge transfer mechanisms in complex systems based on a self-assembled monolayer of guanine molecules adsorbed on a gold surface through different organic linkers. Classical molecular dynamics simulations were carried out to sample the conformational space of both the neutral and the cationic species. Thus, the redox potentials were determined for the ensembles of geometries through multiscale quantum-mechanics/molecular-mechanics/continuum solvation model calculations in the framework of the Marcus theory and in combination with an additive scheme previously developed. In this context, conformational sampling, description of the environment, and effects caused by the linker have been considered. Applying this methodology, we unravel the phenomena of electric current transport by evaluating the different stages in which charge transfer could occur. The results revealed how the positive charge migrates from the organic layer to the gold surface. Specifically, the transport mechanism seems to take place mainly along a single ligand and driven with the help of the electrostatic interactions of the surrounding molecules. Aside, several self-assembled monolayers with different linkers have been analyzed to understand how the nature of that moiety can tune the redox properties and the efficiency of the transport. We have found that the conjugation between the guanine and the linker, at the same time conjugated to the gold surface, gives rise to a more efficient transport. In conclusion, the established computational protocol sheds light on the mechanism behind charge transport in electrochemical DNA-based biosensor nanodevices.

Modeling One-Electron Oxidation Potentials and Hole Delocalization in Double-Stranded DNA by Multilayer and Dynamic Approaches.

The number of innovative applications for DNA nowadays is growing quickly. Its use as a nanowire or electrochemical biosensor leads to the need for a deep understanding of the charge-transfer process along the strand, as well as its redox properties. These features are computationally simulated and analyzed in detail throughout this work by combining molecular dynamics, multilayer schemes, and the Marcus theory. One-electron oxidation potential and hole delocalization have been analyzed for six DNA double strands that cover all possible binary combinations of nucleotides. The results have revealed that the one-electron oxidation potential decreases with respect to the single-stranded DNA, giving evidence that the greater rigidity of a double helix induces an increase in the capacity of storing the positive charge generated upon oxidation. In addition, the hole is mainly stored in nucleobases with large reducer character, i.e., purines, especially when those are arranged in a stacked configuration in the same strand. From the computational point of view, the sampling needed to describe biological systems implies a significant computational cost. Here, we show that a small number of representative conformations generated by clustering analysis provides accurate results when compared with those obtained from sampling, reducing considerably the computational cost.

Ultrafast fragmentation of highly-excited doubly-ionized deoxyribose: role of the liquid water environment.

Ab initio molecular dynamics simulations are used to investigate the fragmentation dynamics following the double ionization of 2-deoxy-D-ribose (DR), a major component in the DNA chain. Different ionization scenarios are considered to provide a complete picture. First focusing on isolated DR2+, fragmentation patterns are determined for the ground electronic state, adding randomly distributed excitation energy to the nuclei. These patterns differ for the two isomers studied. To compare thermal and electronic excitation effects, Ehrenfest dynamics are also performed, allowing to remove the two electrons from selected molecular orbitals. Two intermediate-energy orbitals, localized on the carbon chain, were selected. The dissociation pattern corresponds to the most frequent pattern obtained when adding thermal excitation. On the contrary, targeting the four deepest orbitals, localized on the oxygen atoms, leads to selective ultrafast C-O and/or O-H bond dissociation. To probe the role of environment, a system consisting of a DR molecule embedded in liquid water is then studied. The two electrons are removed from either the DR or the water molecules directly linked to the sugar through hydrogen bonds. Although the dynamics onset is similar to that of isolated DR when removing the same deep orbitals localized on the sugar oxygen atoms, the subsequent fragmentation patterns differ. Sugar damage also occurs following the Coulomb explosion of neighboring H2O2+ molecules due to interaction with the emitted O or H atoms.

One-Electron Oxidation Potentials and Hole Delocalization in Heterogeneous Single-Stranded DNA.

The study of DNA processes is essential to understand not only its intrinsic biological functions but also its role in many innovative applications. The use of DNA as a nanowire or electrochemical biosensor leads to the need for a deep investigation of the charge transfer process along the strand as well as of the redox properties. In this contribution, the one-electron oxidation potential and the charge delocalization of the hole formed after oxidation are computationally investigated for different heterogeneous single-stranded DNA strands. We have established a two-step protocol: (i) molecular dynamics simulations in the frame of quantum mechanics/molecular mechanics (QM/MM) were performed to sample the conformational space; (ii) energetic properties were then obtained within a QM1/QM2/continuum approach in combination with the Marcus theory over an ensemble of selected geometries. The results reveal that the one-electron oxidation potential in the heterogeneous strands can be seen as a linear combination of that property within the homogeneous strands. In addition, the hole delocalization between different nucleobases is, in general, small, supporting the conclusion of a hopping mechanism for charge transport along the strands. However, charge delocalization becomes more important, and so does the tunneling mechanism contribution, when the reducing power of the nucleobases forming the strand is similar. Moreover, charge delocalization is slightly enhanced when there is a correlation between pairs of some of the interbase coordinates of the strand: twist/shift, twist/slide, shift/slide, and rise/tilt. However, the internal structure of the strand is not the predominant factor for hole delocalization but the specific sequence of nucleotides that compose the strand.

MoBioTools: A toolkit to setup quantum mechanics/molecular mechanics calculations.

We present a toolkit that allows for the preparation of QM/MM input files from a conformational ensemble of molecular geometries. The package is currently compatible with trajectory and topology files in Amber, CHARMM, GROMACS and NAMD formats, and has the possibility to generate QM/MM input files for Gaussian (09 and 16), Orca (≥4.0), NWChem and (Open)Molcas. The toolkit can be used in command line, so that no programming experience is required, although it presents some features that can also be employed as a python application programming interface. We apply the toolkit in four situations in which different electronic-structure properties of organic molecules in the presence of a solvent or a complex biological environment are computed: the reduction potential of the nucleobases in acetonitrile, an energy decomposition analysis of tyrosine interacting with water, the absorption spectrum of an azobenzene derivative integrated into a voltage-gated ion channel, and the absorption and emission spectra of the luciferine/luciferase complex. These examples show that the toolkit can be employed in a manifold of situations for both the electronic ground state and electronically excited states. It also allows for the automatic correction of the active space in the case of CASSCF calculations on an ensemble of geometries, as it is shown for the azobenzene derivative photoswitch case.

Intramolecular and intermolecular hole delocalization rules the reducer character of isolated nucleobases and homogeneous single-stranded DNA.

The use of DNA strands as nanowires or electrochemical biosensors requires a deep understanding of charge transfer processes along the strand, as well as of the redox properties. These properties are computationally assessed in detail throughout this study. By applying molecular dynamics and hybrid QM/continuum and QM/QM/continuum schemes, the vertical ionization energies, adiabatic ionization energies, vertical attachment energies, one-electron oxidation potentials, and delocalization of the hole generated upon oxidation have been determined for nucleobases in their free form and as part of a pure single-stranded DNA. We show that the reducer ability of the isolated nucleobases is explained by the intramolecular delocalization of the positively charged hole, while the enhancement of the reducer character when going from aqueous solution to the strand correlates very well with the intermolecular hole delocalization. Our simulations suggest that the redox properties of DNA strands can be tuned by playing with the balance between intramolecular and intermolecular charge delocalization.

Non-ergodic fragmentation upon collision-induced activation of cysteine-water cluster cations.

Cysteine-water cluster cations Cys(H2O)3,6+ and Cys(H2O)3,6H+ are assembled in He droplets and probed by tandem mass spectrometry with collision-induced activation. Benchmark experimental data for this biologically important system are complemented with theory to elucidate the details of the collision-induced activation process. Experimental energy thresholds for successive release of water are compared to water dissociation energies from DFT calculations showing that clusters do not only fragment exclusively by sequential emission of single water molecules but also by the release of small water clusters. Release of clustered water is observed also in the ADMP (atom centered density matrix propagation) molecular dynamics model of small Cys(H2O)3+ and Cys(H2O)3H+ clusters. For large clusters Cys(H2O)6+ and Cys(H2O)6H+ the less computationally demanding statistical Microcanonical Metropolis Monte-Carlo method (M3C) is used to model the experimental fragmentation patterns. We are able to detail the energy redistribution in clusters upon collision activation. In the present case, about two thirds of the collision energy redistribute via an ergodic process, while the remaining one third is transferred into a non-ergodic channel leading to ejection of a single water molecule from the cluster. In contrast to molecular fragmentation, which can be well described by statistical models, modelling of collision-induced activation of weakly bound clusters requires inclusion of non-ergodic processes.

Photofragmentation specificity of photoionized cyclic amino acids (diketopiperazines) as precursors of peptide building blocks.

The photoionisation and photofragmentation of the two cyclic dipetides cyclo(alanyl-glycine) cGA and cyclo(glycyl-glycine) cGG, have been studied combining experiments and simulations. State selected fragments from the ionized molecules are detected using photo-electron photo-ion coincidence (PEPICO) measurements and specific fragmentation paths are identified and characterized via the use of ion-neutral coincidence maps. The simulations, performed using Quantum Chemistry methods, allow us to infer the fragmentation mechanisms of the ionized and excited molecules. We show that ring opening is followed by emission of the neutral fragments CO and HNCO. In the case of cGG the emission of neutral CO leads to a metastable structure that breaks producing small cationic fragments. The studied cyclic dipeptides evolve under ionizing radiation generating different small aziridin moieties and oxazolidinones. These two species are key reactants to elongate producing peptide chains. The corresponding mechanisms have been computed and show that the reaction requires very low energy and may occur in the presence of ionizing radiation.

H2O˙+ and OH+ reactivity versus furan: experimental low energy absolute cross sections for modeling radiation damage.

Radiotherapy is one of the most widespread and efficient strategies to fight malignant tumors. Despite its broad application, the mechanisms of radiation-DNA interaction are still under investigation. Theoretical models to predict the effects of a particular delivered dose are still in their infancy due to the difficulty of simulating a real cell environment, as well as the inclusion of a large variety of secondary processes. This work reports the first experimental study of the ion-molecule reactions of the H2O˙+ and OH+ ions, produced by photoionization with synchrotron radiation, with a furan (c-C4H4O) molecule, a template for deoxyribose sugar in DNA. The present experiments, performed as a function of the collision energy of the ions and the tunable photoionization energy, provide key parameters for the theoretical modelling of the effect of radiation dose, like the absolute cross sections for producing protonated furan (furanH+) and a radical cation (furan˙+), the most abundant products, which can amount up to 200 Å2 at very low collision energies (<1.0 eV). The experimental results show that furanH+ is more fragile, indicating how the protonation of the sugar component of the DNA may favor its dissociation with possible major radiosensitizing effects. Moreover, the ring opening of furanH+ isomers and the potential energy surface of the most important fragmentation channels have been explored by molecular dynamics simulations and quantum chemistry calculations. The results show that, in the most stable isomer of furanH+, the ring opening occurs via a low energy pathway with carbon-oxygen bond cleavage, followed by the loss of neutral carbon monoxide and the formation of the allyl cation CH2CHCH2+, which instead is not observed in the fragmentation of furan˙+. At higher energies the ring opening through the carbon-carbon bond is accompanied by the loss of formaldehyde, producing HCCCH2+, the most intense fragment ion detected in the experiments. This work highlights the importance of the secondary processes, like the ion-molecule reactions at low energies in the radiation damage due to their very large cross sections, and it aims to provide benchmark data for the development of suitable models to approach this low collision energy range.

Resonant Inner-Shell Photofragmentation of Adamantane (C10H16).

Adamantane, the smallest diamondoid molecule with a symmetrical cage, contains two distinct carbon sites, CH and CH2. The ionization/excitation of the molecule leads to the cage opening and strong structural reorganization. While theoretical predictions suggest that the carbon site CH primarily causes the cage opening, the role of the other CH2 site remains unclear. In this study, we used advanced experimental Auger electron-ion coincidence techniques and theoretical calculations to investigate the fragmentation dynamics of adamantane after resonant inner-shell photoexcitation. Our results demonstrate that some fragmentation channels exhibit site-sensitivity of the initial core-hole location, indicating that different carbon site excitations could lead to unique cage opening mechanisms.

Peptide Bond Formation in the Protonated Serine Dimer Following Vacuum UV Photon-Induced Excitation.

Possible routes for intra-cluster bond formation (ICBF) in protonated serine dimers have been studied. We found no evidence of ICBF following low energy collision-induced dissociation (in correspondence with previous works), however, we do observe clear evidence for ICBF following photon absorption in the 4.6-14 eV range. Moreover, the comparison of photon-induced dissociation measurements of the protonated serine dimer to those of a protonated serine dipeptide provides evidence that ICBF, in this case, involves peptide bond formation (PBF). The experimental results are supported by ab initio molecular dynamics and exploration of several excited state potential energy surfaces, unraveling a pathway for PBF following photon absorption. The combination of experiments and theory provides insight into the PBF mechanisms in clusters of amino acids, and reveals the importance of electronic excited states reached upon UV/VUV light excitation.

Preparation, Supramolecular Organization, and On-Surface Reactivity of Enantiopure Subphthalocyanines: From Bulk to 2D-Polymerization.

The development of chiral materials is severely limited by the challenge to achieve enantiopure derivatives with both configurational stability and good optoelectronic properties. Herein we demonstrate that enantiopure subphthalocyanines (SubPcs) fulfill such demanding requirements and bear the prospect of becoming components of chiral technologies. Particularly, we describe the synthesis of enantiopure SubPcs and assess the impact of chirality on aspects as fundamental as the supramolecular organization, the behavior in contact with metallic surfaces, and the on-surface reactivity and polymerization. We find that enantiopure SubPcs remarkably tend to organize in columnar polar assemblies at the solid state and highly ordered chiral superstructures on Au(111) surfaces. At the metal interface, such SubPcs are singled out by scanning tunneling microscopy. DFT calculations suggest that SubPcs undergo a bowl-to-bowl inversion that was shown to be dependent on the axial substituent. Finally, we polymerize by means of on-surface synthesis a highly regular 2D, porous and chiral, π-extended polymer that paves the way to future nanodevice fabrication.

Computation of Oxidation Potentials of Solvated Nucleobases by Static and Dynamic Multilayer Approaches.

The determination of the redox properties of nucleobases is of paramount importance to get insight into the charge-transfer processes in which they are involved, such as those occurring in DNA-inspired biosensors. Although many theoretical and experimental studies have been conducted, the value of the one-electron oxidation potentials of nucleobases is not well-defined. Moreover, the most appropriate theoretical protocol to model the redox properties has not been established yet. In this work, we have implemented and evaluated different static and dynamic approaches to compute the one-electron oxidation potentials of solvated nucleobases. In the static framework, two thermodynamic cycles have been tested to assess their accuracy against the direct determination of oxidation potentials from the adiabatic ionization energies. Then, the introduction of vibrational sampling, the effect of implicit and explicit solvation models, and the application of the Marcus theory have been analyzed through dynamic methods. The results revealed that the static direct determination provides more accurate results than thermodynamic cycles. Moreover, the effect of sampling has not shown to be relevant, and the results are improved within the dynamic framework when the Marcus theory is applied, especially in explicit solvent, with respect to the direct approach. Finally, the presence of different tautomers in water does not affect significantly the one-electron oxidation potentials.

Electron and ion spectroscopy of the cyclo-alanine-alanine dipeptide.

The VUV photoionisation and photofragmentation of cyclo-alanine-alanine (cAA) has been studied in a joint experimental and theoretical work. The photoelectron spectrum and the photoelectron-photoion coincidence (PEPICO) measurements, which enable control of the energy being deposited, combined with quantum chemistry calculations, provide direct insight into the cAA molecular stability after photoionisation. The analysis of the ion-neutral coincidence experiments with the molecular dynamics simulations and the exploration of the potential energy surface allows a complete identification of the fragmentation pathways. It has been found that the fragmentation always starts with the ring opening through the C-C bond cleavage, followed by release of neutral CO or HNCO moieties.

Controlling the diversity of ion-induced fragmentation pathways by N-methylation of amino acids.

We present a combined experimental and theoretical study of the fragmentation of singly and doubly N-methylated glycine (sarcosine and N,N-dimethyl glycine, respectively) induced by low-energy (keV) O6+ ions. Multicoincidence mass spectrometry techniques and quantum chemistry simulations (ab initio molecular dynamics and density functional theory) allow us to characterise different fragmentation pathways as well as the associated mechanisms. We focus on the fragmentation of doubly ionised species, for which coincidence measurements provide unambiguous information on the origin of the various charged fragments. We have found that single N-methylation leads to a larger variety of fragmentation channels than in no methylation of glycine, while double N-methylation effectively closes many of these fragmentation channels, including some of those appearing in pristine glycine. Importantly, the closure of fragmentation channels in the latter case does not imply a protective effect by the methyl group.

Coincidence study of core-ionized adamantane: site-sensitivity within a carbon cage?

We investigate the fragmentation dynamics of adamantane dications produced after core-ionization at the carbon edge followed by Auger decay. The combination of high-resolution electron spectroscopy, energy-resolved electron-ion multi-coincidence spectroscopy and different theoretical models allows us to give a complete characterization of the processes involved after ionization. We show that energy- and site-sensitivity is observed even for a highly-symmetric molecule that lacks any unique atomic site.

Total Electron Detachment and Induced Cationic Fragmentation Cross Sections for Superoxide Anion (O2-) Collisions with Benzene (C6H6) Molecules.

In this study, novel experimental total electron detachment cross sections for O2- collisions with benzene molecules are reported for the impact energy range (10-1000 eV), as measured with a transmission beam apparatus. By analysing the positively charged species produced during the collision events, relative total ionisation cross sections were derived in the incident energy range of 160-900 eV. Relative partial ionisation cross sections for fragments with m/z ≤ 78 u were also given in this energy range. We also confirmed that heavier compounds (m/z > 78 u) formed for impact energies between 550 and 800 eV. In order to further our knowledge about the collision dynamics governing the fragmentation of such heavier molecular compounds, we performed molecular dynamics calculations within the framework of the Density Functional Theory (DFT). These results demonstrated that the fragmentation of these heavier compounds strongly supports the experimental evidence of m/z = 39-42, 50, 60 (u) cations formation, which contributed to the broad local maximum in the total ionisation observed from 550 to 800 eV. This work reveals the reactivity induced by molecular anions colliding with hydrocarbons at high energies, processes that can take place in the interstellar medium under various local conditions.

Synergy Effects in Heavy Metal Ion Chelation with Aryl- and Aroyl-Substituted Thiourea Derivatives.

Detection and removal of metal ion contaminants have attracted great interest due to the health risks that they represent for humans and wildlife. Among the proposed compounds developed for these purposes, thiourea derivatives have been shown as quite efficient chelating agents of metal cations and have been proposed for heavy metal ion removal and for components of high-selectivity sensors. Understanding the nature of metal-ionophore activity for these compounds is thus of high relevance. We present a theoretical study on the interaction between substituted thioureas and metal cations, namely, Cd2+, Hg2+, and Pb2+. Two substituent groups have been chosen: 2-furoyl and m-trifluoromethylphenyl. Combining density functional theory simulations with wave function analysis techniques, we study the nature of the metal-thiourea interaction and characterize the bonding properties. Here, it is shown how the N,N'-disubstituted derivative has a strong affinity for Hg2+, through cation-hydrogen interactions, due to its greater oxidizing capacity.

Imaging intramolecular hydrogen migration with time- and momentum-resolved photoelectron diffraction.

Imaging ultrafast hydrogen migration with few- or sub-femtosecond time resolution is a challenge for ultrafast spectroscopy due to the lightness and small scattering cross-section of the moving hydrogen atom. Here we propose time- and momentum-resolved photoelectron diffraction (TMR-PED) as a way to overcome limitations of existing methodologies and illustrate its performance in the ethanol molecule. By combining different theoretical methods, namely molecular dynamics and electron scattering methods, we show that TMR-PED, along with a judicious choice of the reference frame for multi-coincidence detection, allows for direct imaging of single and double hydrogen migration in doubly-charged ethanol with both few-fs and Å resolutions, all the way from its birth to the very end. It also provides hints of proton extraction following H2 roaming. The signature of hydrogen dynamics shows up in polarization-averaged molecular-frame photoelectron angular distributions (PA-MFPADs) as moving features that allow for a straightforward visualization in space.

Ultrafast molecular dynamics in ionized 1- and 2-propanol: from simple fragmentation to complex isomerization and roaming mechanisms.

Upon photoexcitation, molecules can undergo numerous complex processes, such as isomerization and roaming, leading to changes in the molecular and electronic structure. Here, we report on the time-resolved ultrafast nuclear dynamics, initiated by laser ionization, in the two structural isomers, 1- and 2-propanol, using a combination of pump-probe spectroscopy and coincident Coulomb explosion imaging. Our measurements, paired with quantum chemistry calculations, identify the mechanisms for the observed two- and three-body dissociation channels for both isomers. In particular, the fragmentation channel of 2-propanol associated with the loss of CH3 shows possible evidence of methyl roaming. Moreover, the electronic structure of this roaming methyl fragment could be responsible for the enhanced ionization also observed for this channel. Finally, comparison with similar studies done on ethanol and acetonitrile helps establish a correlation between the length of the alkyl chain and the likelihood of hydrogen migration.