ERC Advanced Grant SUBNANO (2019-2023)

Project coordinator:  Mario Barbatti

Funding: 2 500 000 €

More information: https://barbatti.org/2019/03/28/subnano-erc-adg-2019/

Computational Photochemistry in the Long Timescale:  Sub-ns Photoprocesses in DNA

The goal of the SubNano project is to massively speed up the dynamics simulation of photoexcited molecules to allow addressing sub-nanosecond phenomena (that is, one thousand times above the current limits).

The sub-ns methodology will be employed to investigate the long timescale nonadiabatic dynamics of photoinduced processes in nucleic acids, including DNA photostabilization via excitonic processes, biological fluorescent markers, and transient anion formation in DNA repair.

To fulfill these goals, we will develop and implement a series of methods to extend nonadiabatic dynamics simulations into the new timescale, mainly based on a novel adaptive diabatic machine learning algorithm and a novel zero-point-corrected and vibronically-corrected mixed quantum-classical method.

The sub-ns methodology will be constrained to be general (any kind or size of molecule), black-box (minimum user intervention), modular (adaptable to any electronic structure theory), on-the-fly (no need of precomputed potential energy surfaces), and local (independent-trajectories).

It will be implemented into the Newton-X software platform, which I have been the main designer and developer. It will also be made available for all academic community through new releases of Newton-X.

For the last 25 years, theoretical investigations of photodynamical processes have been restricted to the ultrafast (picosecond) regime, selectively choosing problems in this domain. The extension into the sub-ns regime is finally feasible thanks to a large algorithmic infrastructure our group have built over the last 13 years, paving the grounds to develop a new research area, atomistic nonadiabatic dynamics on the long timescale.

The success of the SubNano project will have an enormous impact on the research field, allowing to investigate outstanding interdisciplinary phenomena in chemistry, biology, and technology, which have been neglected due to a lack of methods.


FET-OPEN BOOSTCROP (2019-2021)

Project coordinator in Marseille:  Mario Barbatti

Consortium:  University of Warwick (coordinator); Aix Marseille University; AgroParisTech; Bundesinstitut für Risikobewertung (BFR); PlantResponse Biotech; Radboud University; University of Amsterdam; University of Bristol

Funding: 306 000 €

More information: https://barbatti.org/2019/07/03/fet-open-2018/

Growth using Natural Product and Synthesis Enabled Solar Harvesting

A major challenge in the twenty-first century is to increase global food production to feed a continuously growing population while the quality and quantity of arable land is diminishing. Central to this problem is the necessity to increase the yield of numerous important crop species and to find ways to extend geographical locations suitable for agriculture. Cold stress is an environmental extreme that hampers crop yield. Low temperatures restrict plant growth and development, while frost causes tissue damage. Yield losses are even more severe when cold stress occurs during the reproductive stage. Breeding programs for new tolerant varieties are diverse and usually tailored to the specific needs of a particular crop. The plant’s response to cold stress, however, is complex, involving many physiological, structural, and biochemical changes, which interact with other environmental factors and metabolic processes. BoostCrop represents a novel approach to improve crop yields by protecting plants from cold stress and stimulating their growth under a range of growing conditions. The invention is based on ‘molecular heaters’ (patent application GB1715528.4 ‘Molecular Heaters’ filed at the UK intellectual property office Sept. 2017); nature-inspired molecules that absorb light at wavelengths that are either harmful to the plant or not used in photosynthesis, and converting this light energy to heat.


ANR-PRC WSPLIT (2018-2021)

Project coordinator:  Mario Barbatti

Consortium:  Gilles Grégoire (Université Paris Sud), Christophe Jouvet (AMU)

Funding: 306 000 €

Photoinduced Water Splitting Dynamics in the Gas Phase

Photoinduced water splitting is the ultimate source of storable and clean energy in the form of H2. For over four decades, to optimize this process has been the grail of sustainable energy research.

The possibility of splitting water through photoinduced radical reactions enabled by a simple organic chromophore is a recent theoretical prediction, which already counts on preliminary experimental corroboration. These reactions, however, are not the ones commonly expected in water splitting processes, as they involve hydrogen radicals rather than protons. For this reason, they may represent a deep paradigm shift in the H2 photocatalysis from water, if a series of bottlenecks in terms of recombination rates can be eliminated.

At this point, not much is known about these radical reactions. The WSplit project has been set up exactly to apply state-of-the-art experimental and computational techniques to close this knowledge gap. The project joins the expertise of three research terms, two experimental and one computational, to disentangle the reactive process through a combination of a large battery of techniques, including theoretical simulations, time-resolved experiments, and laser spectroscopy coupled to mass spectrometry. This analysis will be applied to isolated microsolvated clusters. The goals of the project are:

  • To develop and use advanced experimental and computational methods to characterize the radical dynamics in microsolvated pyridine-water clusters.
  • To use this basic knowledge to search for ways to reduce the recombination rate in these photoreactions.
  • To test the efficiency of this class of radical reactions when photoinduced by other organic chromophores.


ANR-JCJC BIOMAGNET (2017-2021):

Project coordinator: M. Huix-Rotllant
Consortium: M. Huix-Rotllant , N. Ferré , M. Barbatti
Webpage: http://icr-amu.cnrs.fr/tct/biomagnet
Funding: 196.244 €

On the quest of a biological compass: Magnetic field effects on the cryptochrome protein

Abstract: Certain migratory animals orient during their long-distance migrations by perceiving the terrestrial magnetic field. The exact molecular origin of such sense is still unknown. Recently, the cryptochrome protein has been proposed as responsible of such “biological compass”. The photochemical mechanism would be based on the radical pair creation in donor-acceptor complexes: after light absorption, an electron transfer occurs between one flavin and the tryptophans forming the active site of cryptochrome, generating in this way a localized radical pair. Such radical pair would undergo a coherent dynamics of populations of singlet and triplet excited states. Theoretical models have shown that such dynamics can be affected by low-intensity external magnetic fields, supposing that the excited states have specific magnetic and dynamical properties: long-lived radical pairs, different singlet and triplet reactivity, anisotropic hyperfine coupling, etc. To this point, there is no proof that such a mechanism can exist in a biological medium. We propose to develop a multi-scale quantum dynamical model with the objective of determining the effect of magnetic fields to the activity of the cryptochrome protein. This model is based on analytic effectiveHamiltonians, which contain the information of magnetic, electronic and vibrational properties of the excited states of the protein. Such Hamiltonians will be used subsequently to propagate wavepackets in real time under the action of external magnetic fields. The project will give a first proof of whether the cryptochrome protein can be considered as a biological compass. Furthermore, the results can constitute the first direct proof of the effect of a low-intensity magnetic field on the mechanism of a photochemical reaction taking place in a biological medium.

Erithacus_rubecula_with_cocked_head


ANR-PRCi MULTICROSS (2020-2023):

Project coordinator in Marseille: M. Huix-Rotllant
Consortium: M. Huix-Rotllant , M. Cammarata (Institut de Physique de Rennes), H. Lemcke (SwissFEL)

Multiple trajectories towards excited states

Abstract: Multicross aims at understanding transition metal photophysics to a new level of detail thanks to a joint experimental and theoretical research program spanning three laboratories and two countries. Ultrafast optical spectroscopy and X-ray techniques will be pushed to time resolutions approaching 10 fs. Quantum models will be used to solve time dependent Schrodinger equation to follow the photoinduced wavepacket motion and dispersion along different excited state trajectories that will be controlled by different pump laser pulses. Because the same physical model will be able to explain the different experimental findings, the outcomes will be little biased and the resulting representations can be used to clarify the mechanisms behind the unexpected properties of ultrafast intersystem crossing of transition metal compounds. Indeed transition metals play often a central role in photoreceptors, catalysts and biological active sites. This is due to their capability of changing oxidation states (favouring charge transfers) and of being coordinated by different molecular geometries. Typical examples are organometallic systems. Organic ligands lift the degeneracy of 3d orbitals usually resulting in non bonding and antibonding levels. Such energy gap creates different electronic/structural configurations that can be stabilized by enthalpic (low spin, LS) or entropic (high spin, HS) contributions. Spin CrossOver (SCO) from LS to HS state is usually phototriggered by electronic excitation via a metal-to-ligand charge transfer (MLCT) band. Experiments have tried to disclose what immediately follows these excitations and have delivered unexpectedly high intersystem crossing rates. Such observation spurred a wealth of experimental and theoretical investigations all attempting to understand the sub picosecond (1 ps = 10-12 s) LS to HS mechanism and dynamics. Today, while the ultrafast nature of SCO photophysics is undiscussed a detailed understand of the process is still debated. For example, the most studied SCO compound has been scrutinised with optical and X-ray spectroscopy, still yielding completely different switching mechanisms in terms of time scale (from sub-50-fs to nearly 200 fs) and visited intermediates electronic states. The physical picture is even less clear for non octahedral SCO systems that only very recently have been experimentally studied, or hetero-bimetallic compounds in which both charge transfer and spin transition characterize the the difference between low and high temperature phases. Multicross will focus on those different systems in search of an underlying physical picture that could for example evidence the role of particular structural degrees of freedom in driving the system to the metastable HS state.

Image reproduced from Nat. Comm. 8, 15342 (2017).


 

ANR-PRC BIOLUM (2017-2020):

Project coordinator: N. Ferré
Consortium: V. Ledentu, N. Ferré (AMU), MSME (Marne-la-Vallée), LBP (Strasbourg), IPCMS  (Strasbourg)
Funding: 
442.669 €

Molecular Origin and Modulation of the Color in Firefly Bioluminescence

Abstract: Vision and other light-based signaling processes are ubiquitous in Nature. Among all the molecular mechanisms responsible for light emission (eg fluorescence, phosphorescence …), chemiluminescence and its corresponding process in living organisms, bioluminescence, are interesting because of their molecular origin: chemical energy converted to light. It is noteworthy that the emitted light is a signature of the underlying chemical reaction. Hence bioluminescence has inspired the development of many analytical toolboxes in biomedical applications (eg imaging) using analogues of typical light emitters (fireflies, beetles, jellyfishes, …) Because these analogues exhibit photochemical properties similar to their natural counterparts (luminophores), they usually emit blue and green colors, i.e. synthetic yellow or red light emitters remain scarce. The design of bio-inspired light emitters requires a deeper understanding of the factors responsible at the molecular level for the tuning of the emitted color. As exemplified by the design of Green Fluorescent Protein (GFP, 2008 Nobel Prize in Chemistry)-like systems with optimum photophysical properties, it is of paramount importance to deeply understand the interactions between the light-active species and their protein binding pocket. Similar achievement is needed for the development of bioluminescence-based highly sensitive analytical techniques in environmental, medical, food analysis to cite just a few. The BIOLUM project aims to combine state-of-the-art theoretical and experimental fundamental researches to assess the effect of two major color tuning factors: 1) the luminophore + protein structures and interactions, 2) pH. Crossing the informations accumulated for both native and modified luciferin luminophores in the paradigmatic firefly luciferase enzyme, we envision an improved picture of the mechanisms at work in color modulation, with focus on 1) structures of native and modified luciferins in the luciferase binding pocket, 2) relevant photochemical steps in light emission, 3) key proton transfers between oxyluciferin (denoting the very last luciferin structure before light emission) and various donors and acceptors and 4) amino acids of the protein binding pocket that are crucial to control light emission color. Finally, the gained knowledge will help to suggest new directions for the rational design of man-taylored chemi- and bio-luminescent systems with selected colors.

firefly-pics2



A*MIDEX Emergence & Innovation Pyrenex (2019-2022)

Project coordinator: M. Gingras (CINAM-AMU)
Consortium: D. Siri, A. Gaudel-Siri (ICR-AMU), D. Gigmes (ICR-AMU), J.V. Naubron, M. Giorgi (FR1739-AMU)
Funding: 
212.495 €

Pyrene as Universal Building Block for the Design of π-Conjugation and Topology in Organic Electronics: from Chains to Ribbons and Helices

Abstract: Pyrene is a remarkable chromophore in view of its excited-state properties and the dependence of its fluorescence upon the environment. Transition to pyrene oligomers and polymers, the key concept of this joint proposal, opens important questions as to the delocalization of excitons and the mechanisms of energy transfer between the subunits. Such features will sensitively depend upon the way in which the pyrene moieties are connected. This is why we target both linear and ribbon structures, with direct aryl-aryl couplings or with additional sulfide bridges, thereby even including extended p-systems with helicity (chirality). It is innovative to combine sulfur and pyrene chemistry, in order to create new building blocks, which will themselves serve to create conjugated 2D or 3D geometrical objects of various topologies. This project will also tackle the relation between topology and opto-electronic properties, for opening up a new direction and future perspectives in materials science and in polyaromatic chemistry.

Summary of the objectives:

  1. to create simple regioselective/regiospecific pyrene poly- and hetero- functionalization (including sulfuration and/or fluorination) for making soluble building blocks to be of some used in the synthesis of poly(hetero)pyrene architectures
  2. to gradually increase the complexity of polypyrenes from monomoner to dimers, to oligomers and to polymers in order to effect the photochemical and electronic characterization of those entities, with a regard on coupling mode, exciplexes, energy transfer, charge-transfer states, redox, structural studies, and calculations to help in understanding these properties
  3. to explore those events in case of some specific supramolecular environments, solvation, etc
  4. to draw some conclusions on the effect of topology on those photophysical characteristics, opto-electronic properties and energy transfer

To reach the aims of this project, a deep insight on the reactivity of pyrenes is required. Hence, to get reliable kinetic and thermodynamic data, we need to calculate accurate activation and reaction energies. These calculations will be performed with Gaussian 09 software.
Due to the size and the large electron delocalization of these molecules, we plan to test some DFT methods:
– pure DFT methods with dispersion correction like B97D
– classical hybrid functionals (PBE0, BMK, M06-2X)
– classical hybrid functionals with dispersion correction like  wB97-XD
– composite QM/MM approach
The basis set effects (importance of triple- z valence orbitals, dispersion functions and polarization functions) will be also considered.
The chosen method will be used to interpret and predict:

  • Reaction pathways for the design of pyrene monomers
  • Effect of oligomer topology on photochemical properties using TD-DFT methods
  • Calculations of some properties like HOMO/LUMO orbitals, redox potentials, electron delocalization map, …


ANR-PRC shapeNread (2020-2023)

Project coordinator: L. Charles (AMU)
Consortium: L. Charles, D. Siri, A. Gaudel-Siri (AMU), ICS (Strasbourg), IPHC (Strasbourg)
Funding: 511.715 €

Conformational design for high throughput MS/MS reading of digital polymers

Abstract: The general scientific context of this project is massive and long-term data storage, with the need for alternative media to hard disks that are currently employed and require energy-consuming data centers to store quintillion bytes of data generated every day. A key issue is to increase storage density, that is, to lower the size occupied by each binary digit (or bit) used to code digital information. Compared to the tens of nanometers of each bit in current hard disks, targeted storage densities require bit size in the nanometer range or below, that is, the atomic or molecular scale. Recent new concepts propose to use polymers with a controlled sequence of monomers respectively defined as the 0-bit and 1-bit of the ASCII code. Such information-containing polymers can be biological (e.g. DNA) or abiotic, and retrieving information from such molecular media typically consists of chain sequencing. During the last few years, our group has demonstrated that digital information can be stored in the sequence of various synthetic macromolecules that were produced as highly monodisperse species. Because the 0/1 coding system used in these polymers was based on mass variation between the two units, tandem mass spectrometry (MS/MS) was systematically used as an efficient sequencing method to “read” information “written” in the chains. Our group recently reported that MS/MS sequencing of long coded polymer chains can be achieved through careful macromolecular design.

Molecular modeling will be performed to calculate CCS variation of primary fragments upon substitution of the tagging moiety in order to predict their separation efficiency by IMS. In order to select most relevant calculation methods, theoretical CCSs will first be evaluated for fragments studied in our preliminary experiments and compared to experimental values derived from measured drift times in IMS. In order to validate the most appropriate theoretical method, two computational protocols will be investigated: (i) conformational analysis by simulating annealing with a semi-empirical method, with selected conformers optimized at DFT level and Boltzmann-weighted CCS calculated using MOBCAL software, and (ii) molecular dynamics simulation, performed using GAFF force field and Barone’s parameters for the nitroxide moiety. Geometry snapshots will be used for CCS calculation. Attention will be paid to the ability of biradical fragments to form a macrocycle by recombination. Biradical singlet state and triplet state will be carefully considered (CASSCF method compared to BS-DFT methods). Byte co-monomeric sequence has no significant influence on their drift time (and hence on their CCS), which increases linearly with the number of 1 bits. Molecular modeling will also have to be performed at different energy levels in order to investigate the folding/unfolding process of bytes as a function of their tag, in conjunction with IMS experiments conducted in denaturing conditions.