Computational Modelling of Excited State Decay in Polyatomic Molecules

The introduction of general numerical methods in the form of widely available software can have a dramatic effect on the development of a scientific field. In electronic structure theory, for example, general-purpose programs (such as Gaussian, ADF, MOLPRO,. . . ) combined with better computational resources have in part led to molecular electronic structure calculations becoming a ubiquitous tool in chemical research. Similarly, quantum dynamics methods based on coupled time-evolving Gaussian basis sets and molecular potential energy surfaces calculated on-the-fly hold out similar promise in the study of non-adiabatic processes, because of their generality and freedom from ad hoc assumptions. Therefore, the aim of this thesis is to investigate the convergence and applicability of quantum dynamics calculations with a fully variational coupled Gaussian basis set description, termed variational Multi-Con guration Gaussian (vMCG). It is suggested that the vMCG approach provides a way to balance accuracy against computational cost for molecules of comparable size by choosing the number of coupled Gaussian product basis functions and a middle way forward between grid-based and trajectory surface hopping approaches to non-adiabatic molecular quantum dynamics calculations. In order to prove the suitability of vMCG we show its application to three problems of chemical interest: the study of fulvene excited state decay, the prediction of a coherent control mechanism for the same system and the benchmarking of an electronic population dynamics model for electronic transitions when occurring through a conical intersection. In the long term, the development of vMCG is expected to have a major impact, allowing nonadiabatic dynamics simulations to be made not only by theoreticians, but also by non-specialists and experimentalists in both industry and academia.Chapter 1: Modelling Excited State Decay [Diagrams appear here. To view, please open pdf attachment] This chapter introduces and reviews the current state-of-the-art modelling of non-adiabatic processes in molecular systems. This is a challenging topic since the simulation must treat simultaneously the motion of the nuclei and the electrons, which are coupled together. It is concluded that a wide range of methodologies are available. However, when looking for a general tool for the study of non-adiabatic processes, quantum dynamics methods based on coupled time-evolving Gaussian basis sets such as the Direct Dynamics variational Multi-Con guration Gaussian (DD-vMCG) wavepacket method, as well as to other related methods - such as Ab Initio Multiple Spawning (AIMS, FMS)[1, 2] and Multi-Con gurational Ehrenfest (MCE)[3, 4] - seem to be an especially suitable choice because of their generality and freedom from ad hoc assumptions. Chapter 2: variational Gaussian nuclear wavepackets [Diagrams appear here. To view, please open pdf attachment] This chapter describes three possible time-evolving Gaussian basis sets for use in non-adiabatic quantum dynamics based on the Direct Dynamics variational Multi-Con guration Gaussian (DD-vMCG) wavepacket method. These general model representations are compared using model calculations in a simple harmonic oscillator and describing their connections to other work. It is suggested that the fully variational nuclear wavefunction, termed vMCG (variational Multi-Con guration Gaussian) is a very convenient formulation leading towards a realistic sampling of the phase space without the initial conditions (i.e. initial disposition and momentum) being so important when using a su cient amount of coupled Gaussian basis functions. Chapter 3: Fulvene S1/S0 Excited State Decay [Diagrams appear here. To view, please open pdf attachment] The vMCG (variational Multi-Con guration Gaussian) approach described in Chapter 2 is benchmarked in a realistic system by modelling the radiationless decay from an electronic excited state through an extended conical intersection seam. As a benchmark system, we model the radiationless decay of fulvene from its rst electronic excited state and monitor two associated properties: the spatial extent to which the conical intersection seam is sampled and the timescale and stepwise nature of the population transfer. We illustrate how the use of a fully variational nuclear wavefunction provides a way to balance accuracy against computational cost for molecules of comparable size by choosing the number of coupled Gaussian product basis functions. Chapter 4: Controlling Fulvene S1/S0 Decay [Diagrams appear here. To view, please open pdf attachment] Direct quantum dynamics simulations using the vMCG (variational Multi- Con guration Gaussian) approach were performed in order to model the control of the stepwise population transfer in fulvene. As shown in Chapter 3, ultra-fast internal conversion takes place centred on the higher-energy planar/sloped region of the S1/S0 conical intersection seam. Therefore, two possible schemes for controlling whether stepwise population transfer occurs or not | either altering the initial geometry distribution or the initial momentum composition of the photo-excited wavepacket - were explored. In both cases, decay took place instead in the lower-energy twisted/peaked region of the crossing seam, switching o the stepwise population transfer. This absence of re-crossing is a direct consequence of the change in the position on the intersection at which decay occurs and its consequences should provide an experimentally observable fingerprint of this system. Chapter 5: A population transfer model for intramolecular electron transfer [Diagrams appear here. To view, please open pdf attachment] The aim of this chapter is to further prove the applicability of the vMCG (variational Multi-Con guration Gaussian) approach by benchmarking an approximate population dynamics model in Jahn-Teller systems. The socalled Density Matrix Non-Equilibrium Fermi Golden Rule (DM-NFGR) can be seen as a simpli ed version of vMCG, in which the nite Gaussian basis set and on-the-fly evaluation of the nuclear Hamiltonian are eliminated via use of the density matrix formalism and a perturbational treatment of the equations. This has three clear advantages: firstly, it allows us to extend the maximum molecular size considerably; secondly, we can relate the population dynamics to an analytical time-dependent rate expression; and finally, temperature effects can be included in the simulations. Benchmark calculations for the 2,6-bis(methylene) adamantyl (BMA) radical cation support the reliability of the results

Rational Design of Phe‐BODIPY Amino Acids as Fluorogenic Building Blocks for Peptide‐based Detection of Urinary Tract Candida Infections

Fungal infections caused by Candida species are among the most prevalent in hospitalized patients. However, current methods for the detection of Candida fungal cells in clinical samples rely on time‐consuming assays that hamper rapid and reliable diagnosis. Herein, we describe the rational development of new Phe‐BODIPY amino acids as small fluorogenic building blocks and their application to generate fluorescent antimicrobial peptides for rapid labelling of Candida cells in urine. We have used computational methods to analyse the fluorogenic behaviour of BODIPY‐substituted aromatic amino acids and performed bioactivity and confocal microscopy experiments in different strains to confirm the utility and versatility of peptides incorporating Phe‐BODIPYs. Finally, we have designed a simple and sensitive fluorescence‐based assay for the detection of Candida albicans in human urine samples

Acid‐Resistant BODIPY Amino Acids for Peptide‐based Fluorescence Imaging of GPR54 Receptors in Pancreatic Islets

The G protein-coupled kisspeptin receptor (GPR54 or KISS1R) is an important mediator in reproduction, metabolism and cancer biology; however, there are limited fluorescent probes or antibodies for direct imaging of these receptors in cells and intact tissues, which can help to interrogate their multiple biological roles. Herein, we describe the rational design and characterization of a new acid-resistant BODIPY-based amino acid (Trp-BODIPY PLUS), and its implementation for solid-phase synthesis of fluorescent bioactive peptides. Trp-BODIPY PLUS retains the binding capabilities of both short linear and cyclic peptides and displays notable turn-on fluorescence emission upon target binding for wash-free imaging. Finally, we employed Trp-BODIPY PLUS to prepare some of the first fluorogenic kisspeptin-based probes and visualized the expression and localization of GPR54 receptors in human cells and in whole mouse pancreatic islets by fluorescence imaging

Barocaloric properties of quaternary Mn3(Zn,In)N for room-temperature refrigeration applications

The magnetically frustrated manganese nitride antiperovskite family displays significant changes of entropy under hydrostatic pressure that can be useful for the emerging field of barocaloric cooling. Here we show that barocaloric properties of metallic antiperovskite Mn nitrides can be tailored for room-temperature application through quaternary alloying. We find an enhanced entropy change of |¿St|=37JK-1kg-1 at the Tt=300K antiferromagnetic transition of quaternary Mn3Zn0.5In0.5N relative to the ternary end members. The pressure-driven barocaloric entropy change of Mn3Zn0.5In0.5N reaches |¿SBCE|=20JK-1kg-1 in 2.9 kbar. Our results open up a large phase space where compounds with improved barocaloric properties may be found.Peer ReviewedPostprint (author's final draft

Quantum effects in ultrafast electron transfers in cytochrome

peer reviewe

Barocaloric properties of quaternary Mn3(Zn,In)N for room-temperature refrigeration applications

The magnetically frustrated manganese nitride antiperovskite family displays significant changes of entropy under hydrostatic pressure that can be useful for the emerging field of barocaloric cooling. Here we show that barocaloric properties of metallic antiperovskite Mn nitrides can be tailored for room-temperature application through quaternary alloying. We find an enhanced entropy change of |ΔSt|=37JK−1kg−1 at the Tt=300K antiferromagnetic transition of quaternary Mn3Zn0.5In0.5N relative to the ternary end members. The pressure-driven barocaloric entropy change of Mn3Zn0.5In0.5N reaches |ΔSBCE|=20JK−1kg−1 in 2.9 kbar. Our results open up a large phase space where compounds with improved barocaloric properties may be found

A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies

Immunotherapy promotes the attack of cancer cells by the immune system; however, it is difficult to detect early responses before changes in tumor size occur. Here, we report the rational design of a fluorogenic peptide able to detect picomolar concentrations of active granzyme B as a biomarker of immune-mediated anticancer action. Through a series of chemical iterations and molecular dynamics simulations, we synthesize a library of FRET peptides and identify probe H5 with an optimal fit into granzyme B. We demonstrate that probe H5 enables the real-time detection of T cell-mediated anticancer activity in mouse tumors and in tumors from lung cancer patients. Furthermore, we show image-based phenotypic screens, which reveal that the AKT kinase inhibitor AZD5363 shows immune-mediated anticancer activity. The reactivity of probe H5 may enable the monitoring of early responses to anticancer treatments using tissue biopsies