Rational design of photoactive molecules using "black box" quantum dynamics simulations

A rapidly-growing number of industrial, technological and healthcare processes are built around using the energy of absorbed light to drive chemical reactions or energy transfer; for example, photocatalysts use absorbed light to perform chemical reactions which might be otherwise impossible, conjugated polymers are being incorporated into new lightweight photovoltaic devices to convert light into energy, and several photosensitizing drugs are now approved for photodynamic therapies to treat cancers.

To design the next-generation of photoactive molecules with targeted properties, it is essential that we are able to understand and rationalise the mechanism of light-induced chemical reactions; this is where computer simulations can be transformative. Unfortunately, modelling photochemical dynamics is one of the most difficult frontier challenges of computational chemistry; studying the coupled motions of all of the electrons and nuclei in a molecule after it absorbs light requires highly-specialized computer simulation methods (in particular, quantum wavefunction propagation on multiple electronic states), and so has remained the domain of highly-specialized experts.

Our recent work has begun to transform the landscape of this field by combining machine-learning strategies with accurate wavefunction propagation methods; our emerging "on the fly" quantum dynamics strategy now enables us to perform simulations of photochemical dynamics in a matter of hours to days, whereas the established methodology which has prevailed during the last two decades (e.g. grid-based wavefunction propagation on global potential energy surfaces) typically requires months of simulation- and user-time.

The "big idea" of this proposal is to take these new emerging quantum simulation methods and transform them into a true "black box" tool which can be used, by experts and non-experts alike, to perform accurate simulations of photochemical dynamics. This will require an initial period of software and methodology development to improve the usability and efficiency of our exisiting approach. To further increase the scope of our on-the-fly simulation methods, we will then develop strategies which can explicitly account for the influence of solvent molecules on photochemical dynamics; after all, most interesting photo-driven processes take place in solution or solid-phases.

These method developments will then open the gateway to an enormous range of new applications of photochemical dynamics simulations. In this proposal, we identify two state-of-the-art applications which we will be able to address once our "black box" quantum dynamics methodology has been established. First, we will design new universal fluorophore tags which exhibit environment-dependent fluorescence spectra; these tags might find application in bioimaging applications, provide new insights into cellular environments, or in detecting contaminants in water pipes. Second, we will design new photo-acid catalysts for activating olefins, molecules which constitute a large fraction of crude oil but which generally have low commerical value; we will investigate a new photocatalysis method which might be able to transform these chemicals into much higher value commodity chemicals. In a unique twist, both of these applications of quantum simulations will run in tandem with experimental synthesis and spectroscopic characterisation. This will provide a route to validating (and improving!) our simulation methods, and will also function as a feedback loop to enable true computer-driven rational design of photoactive molecules.

Overall, this proposal will seamlessly integrate computational method development and high-impact applications in cutting-edge photochemical sensing and catalysis. Bringing together experts in simulation, spectroscopy and synthesis, our research team is uniquely positioned to deliver on these promising new research directions.

This proposal will deliver an important new simulation capability: direct and accurate simulation of excited-state molecular dynamics in complex environments. By teaming with synthetic chemists and spectroscopists, we will demonstrate how simulation can not only rationalise, but directly guide, molecular design. The long-term impact potential is enormous.

Specific impacts include:

(1) New software tools for quantum dynamics: Our on-the-fly quantum dynamics methodology, including the significant improvements to be addressed in this proposal, will offer a completely unique and state-of-the-art capability to the chemical science community. Computational chemists will benefit from a new tool to perform accurate simulations of photochemical dynamics in solution-phase, enabling simulations of a range of important photofunctional molecules such as fluorescent sensors and photocatalysts. Experimental chemists, such as spectroscopists, will benefit from a powerful yet user-friendly simulation tool which will enable them to correlate experimental observables (e.g. quantum yields, timescales) with coupled electron/nuclear molecular dynamics, allowing unprecedented levels of access to light-driven photochemical dynamics; this in turn will enable rational design of better, more efficient and more responsive photofunctional materials for applications as sunscreens, light-harvesters, sensors, and more.

We anticipate that this research will also have an important impact on UK software infrastructure to enable next-generation computational science; the simulation methods to be developed and applied in this research will position Quantics as a unique and powerful software tool for molecular simulations of a wide variety of photoactive molecules in different environments. By demonstrating the utility of Quantics in designing and analysing the photoactivity of fluorophores and photocatalysts, this research will position Quantics as a major research tool alongside other widely-used simulation codes such as CASTEP, NWChem and Gaussian.

(2) Universal fluorophore tags: Our research will be the first simulations of the non-adiabatic dynamics of designer universal fluorophore tags which account for complex solvent environments. These ambitious simulations will enable us to investigate the design rules of solvent-dependent fluorescent tags, demonstrating a rational-design approach to the community of synthetic chemists aiming to develop new chemical sensors. As well as suggesting new design rules, we will explore commercialisation potential (along with experimental partners and existing industrial links) of these fluorophore tags as this research progresses. In the best-case scenario imaginable, we would aim to license designed fluorophores to chemical distributors, an approach which could have an impact on a wide range of bioimaging research.

(3) Photoacid catalysis: Our proposed photoacid catalysis for olefin activation is, to the best of our knowledge, an entirely new approach to this problem. By developing new photoacids which undergo large pKa shifts under irradiation, and also bind olefin substrates in reactive conformations, this research could open new doorways to investigate olefin activation and the more general field of binding photoacid catalysis. Again, this would certainly be of interest to synthetic chemists in academia, as well as the large community of industrial and pharmaceutical synthetic chemists. By performing selective olefin activation under mild thermal and acid conditions, our approach could clearly extend the chemist's arsenal of reactions.

(4) People, skills and knowledge transfer: This project will bring together a team of 5 experienced academics, 1 research CoI, and 1 PDRA, as well as any associated UG/PG project students who join the team as the project progresses. The opportunities for developing high-level scientific training in a state-of-the-art project setting will clearly benefit all involved.