IRP MAITAIFrench-Australian International Research Project in Chemistry
The IRP “MAITAI” focusing on Multiphoton Absorbers in Therapy and Imaging is a joint CNRS-ANU initiative in chemistry built on a strong collaborative French-Australian consortium involving synthetic molecular chemists, physical chemists, and biochemists. It primarily focuses on molecular photonics, but also on molecular electronics as a means to impart specific photonic properties to discrete molecular (sub)nano-sized architectures. It involves 23 Australian and French researchers mainly located at the Institute of Chemical Sciences of Rennes (ISCR), a joint CNRS-University of Rennes 1 unit (UMR CNRS6226), and at the Australian National University, and constitutes the continuation of the CNRS International Associated Laboratory (LIA) Redochrom.
Missions and research themes
Multiphoton absorption (MPA) is the simultaneous absorption of two or more photons by a molecule or material. This phenomenon can be important as a means to effect optical limiting, which can be employed for the protection of sensitive optical devices including eyes. In addition to the protection of optical devices, the simultaneous absorption of two or more photons (upconversion) can afford other useful outcomes that are a consequence of photophysical processes subsequent to the initial MPA photo-excitation. Radiative decay to the ground-state can release a photon of much greater energy than the initial excitation (multi-photon-excited fluorescence). Relaxation to the ground-state via triplet states (for which subsequent decay is slower) leads to multi-photon-excited phosphorescence. Energy transfer from the excited singlet or (more usually) triplet states to triplet oxygen can afford cytotoxic singlet oxygen (multi-photon photodynamic therapy). Because the initial MPA excitation occurs only where the light intensity is sufficiently intense, the resultant photophysical processes can be realised with exquisite control over interaction volume, resulting in exceptional localization. As a result, MPA has been shown to have potential use in 3D data storage, and photo-initiated polymerization and microfabrication, as well as the aforementioned singlet oxygen photosensitization. These light intensity-dependent highly-localized MPA effects occurring at the focal point of a laser beam can be used in medical imaging and targeted photodynamic therapy, and these are the primary concerns of the new CNRS IRP MAITAI.
MAIN OBJECTIVES OF THE PROJECT
Although particular organic molecules can exhibit moderate-to-large MPA cross-sections, high quantum yields, and/or biocompatibility, their overall performance is often insufficient. Thus, their MPA merit is poor or non-existent at longer wavelengths (particularly the NIR-II region), and they do not usually possess the flexible functionality needed to permit targeting or remote triggering. Some members of the new MAITAI team have demonstrated that certain organometallics can possess exceptional (world-record) values of MPA cross-sections at the key longer wavelengths for biological applications and have shown that the MPA performance can be switched by a range of orthogonal stimuli including some not available to organics. For these reasons, organometallics are a major focus of this IRP. Other members of the MAITAI team have demonstrated expertise in addressing the other key requirements: effecting high luminescence quantum yields, favouring production of singlet oxygen whenever required, engineering biocompatibility, designing and synthesizing therapeutic and theranostic molecules, and incorporating and controlling functionality that can serve as molecular triggers. The CNRS IRP MAITAI will exploit the unique collective expertise of the Australian-French consortium to drive the development of exceptionally efficient multi-photon absorbers from concept through to their applications in therapy and imaging.
institutions and laboratories involved
- Frederic Paul (DR CNRS, PI), UMR CNRS 6226 (ISCR-COrInt Team)
The consortium of French researchers at Institut des Sciences Chimiques de Rennes (ISCR) led by F. Paul belongs to different groups and teams at ISCR. Besides the strong organic or organometallic chemical synthesis component which is shared by most French participants of ISCR (metal-alkynyl complexes; porphyrins; isocyanurates; organic chromophores and fluorophores), some team members bring more specific expertise in various physico-chemical fields (silicon surface functionalization and electrochemistry, mixed-valent compounds, second-order and third-order NLO studies). The latter are complemented by ultrafast transient absorption spectroscopic facilities at the Institute of Physics of Rennes (M. Lorenc, IPR). There is also a strong computational component present among the French delegates (led by J.-F. Halet and A. Boucekkine at ISCR), complemented by a specialist in excited-state calculations in Toulouse (I. Dixon, LCPQ – Univ. Paul Sabatier). On the more bio-oriented front, the French team has been complemented by a group specializing in targeted vectorization and the controlled release of various (hydrophobic) bio-active species using customized polymer nanoparticles (S. Cammas-Marion), a group experienced in theranostics (G. Lemercier, ICMR – Univ. Reims Champagne-Ardennes), and a group (M. Gary-Bobo, IBMM – Univ. Montpellier) equipped for bioimaging, allowing access to a broad range of spectrometers for fluorescence imaging specially equipped for in vivo and in vitro studies and with access to various types of cell lines and living samples. A related facility at Rennes-Villejean may also be used for similar purposes (BIOSIT).
- Mark G. Humphrey (Prof, PI), Research School of Chemistry, ANU (Canberra)
The team of M. G. Humphrey, M. P. Cifuentes, M. S. Kodikara, and M. Morshedi at ANU in Canberra has long-standing experience in organometallic, organic, coordination complex and polymer synthesis, a wide range of spectroscopic, electrochemical and variable temperature UV-vis-NIR-IR spectroelectrochemical techniques, computational studies (DFT/TD-DFT using Gadi, the fastest supercomputer in the southern hemisphere), electron microscopy, and X-ray structural studies. The group also has expertise and equipment to study nonlinear optical properties of molecules (a ns laser for hyper-Rayleigh scattering measurements of quadratic nonlinearities; a tunable fs laser for Z-scan measurements of cubic nonlinearities; and a tunable ns laser for optical limiting studies, all housed in a purpose-built temperature, humidity, and dust-controlled clean room). N. Cox manages Australia’s premier electron paramagnetic resonance (EPR) facility, which operates at the X-band, Q-band, and W-band frequencies in either continuous wave or pulse configuration, and allows in situ light excitation (UV/vis/NIR), electrochemistry, stop-flow/quench flow kinetics and gas exchange measurements along with transient EPR, for characterizing short-lived photo-generated states, complemented by unique magneto-optical facilities. L. R. Malins has a fully-equipped synthetic chemistry laboratory and the necessary resources for synthetic organic chemistry as well as peptide and protein synthesis.
Laser suite for the study of nonlinear optical properties of molecules (Australian National University).
P. J. Low at UWA in Perth has leading expertise in the design, synthesis and study of organic and organometallic compounds exhibiting NIR absorption processes arising from intramolecular electron-transfer processes, and molecular electronics. G. A. Koutsantonis has extensive experience in mixed valence chemistry (organic and organometallic examples), carbon-rich and all carbon ligands on late transition metal fragments, the physical and surfactant properties of metallosurfactants, and molecular electronics including switching of conductance, molecular rectification, and metal complexes in molecular electronics. In addition to synthetic chemistry facilities, their groups have a world-class spectroelectrochemical suite for studying redox-switchable absorption processes and one of the few experimental facilities in the world for the characterisation of electron-transfer processes between molecules and surfaces at the single molecule level.
SPM platform for electrochemical AFM/STM experiments (University of Western Australia).
Single molecule electronic studies and spectroelectrochemical facility (University of Western Australia).
L. M. Rendina at the University of Sydney has extensive expertise in the synthesis and application of boron agents and lanthanoid metal complexes as cancer therapeutics and theranostics, respectively. His group has reported first-in-class, tumour-selective theranostics based on Gd3+ for human glioma. More recently, his group has studied the delivery of radiometals to tumour sites by means of unique ligand structures, and has developed cellular optical probes that exploit the unique luminescence of certain lanthanoid metal ions (e.g. Eu3+ and Tb3+) possessing information-rich emission profiles and long luminescence times.
M. Massi at Curtin University in Perth focuses on photoactive transition metal and lanthaoid complexes as models for fundamental photophysical studies (e.g. unravelling the intricate mechanisms of lanthanoid sensitisation), as well as having applications in the life sciences. His group developed transition metal complexes with specific interactions for polar lipids that are effective in revealing cancer phenotypes, and mitochondria-targeting complexes for staining preserved tissue, bypassing the need for laborious and expensive antibody staining.
The Australian border closure in 2020 in response to the pandemic has prevented all trans-national exchanges since the creation of the MAITAI IRP. Exchanges will resume as soon as borders reopen.
Participants of the Molecular Electronics and Photonics Meeting (MEP 2018), July 10-13, 2018, UR1)
Signing of the first French-Australian SCF-RACI kindred agreement (2018-2022) by the Presidents of SCF (G. Chambaud, left) and RACI (P. Junk, right).
G. A. Koutsantonis at the French-Australian Scientific Day (FASD 2019), April 2019, UR1 (left)
Docteur Honoris Causa nomination of M. G. Humphrey by UR1 (F. Paul left, F. Mongin Right).
Participants of French-Australian MC2R meeting (MCR2 2018), ANU, November 20, 2018.
Program of first French-Australian School on Molecular Electronics and Molecular Photonics (MEMP 2019), ANU, July 4-8, 2019.