Combining Magnetic Spectroscopy and Modern Multireference Methods to Understand the Properties of Bio-Inspired and Enzymatic Multicopper Systems

铜的活性中心起着重要的生物作用，包括电子传递、氧结合、活化和还原以及反硝化过程。酶铜中心在几何结构和电子结构上极其不同，范围从单核中心到双核、三核和四核簇合物。当磁性活性的铜(II)离子在附近存在或通过化学键相互作用时，它们的未配对的自旋矩耦合导致了丰富的磁性和光谱唯象。这主要是通过电子顺磁共振(EPR)技术来探索的，并用自旋哈密顿参数来表示，如交换耦合常数、金属和配体中心的超精细/超精细耦合作用以及局部/全局零场分裂参数。如果涉及多个铜(II)中心，如多铜氧化物酶的三核中心和N2O还原酶的四核CuZ中心，则磁相互作用和相关的光谱行为可能会变得复杂，因此电子结构的唯一指定可能需要结构和光谱特征的量子化学映射。被广泛应用的单行列式密度泛函理论(DFT)方法往往难以正确地描述铜(II)格位之间的磁性相互作用，并且在再现自旋独立可观测值或预测自旋哈密顿量的非海森堡项方面表现不一致。多参考相关波函数方法，如差分专用组态相互作用(DDCI)更可靠，但受到简单的、通常为双核系统的成本的限制，并且不能提供对许多光谱观测的访问。密度矩阵重整化群(DMRG)可以解除这样的限制，它使多参考计算能够在空前大的活动空间中进行。该项目涉及一种实验和理论相结合的方法，其中法国合作伙伴将合成仿生多核铜配合物并对其进行光谱表征，包括使用自旋投影方法基于密度泛函对其性质的描述，而德国合作伙伴将在这些合成模型上开发和应用基于DMRG的多参考方法。一个主要和新颖的目标是建立DMRG和基于DMRG的新技术对多铜体系的磁性和光谱的适用性。合成、光谱和理论相结合的目的是首先建立解释多铜配合物的电子结构、磁性和光谱的基础，将成熟的理论方法应用到酶系统的模型中，以了解生物无机中心本身的性质和功能，最后为生物多铜中心的改进的光谱和潜在的功能类似物的合成提供信息。

Copper active sites play central biological roles, including electron transfer, dioxygen binding, activation and reduction, as well as denitrification processes. Enzymatic copper centers are extremely diverse in geometric and electronic structure, and range from mononuclear sites to dinuclear, trinuclear and tetranuclear clusters. When magnetically active Cu(II) ions are present in proximity or interact through chemical bonds, their unpaired spin moments couple leading to a rich phenomenology in terms of magnetism and spectroscopy. This is mainly probed by electron paramagnetic resonance (EPR) techniques and expressed in terms of spin Hamiltonian parameters such as exchange coupling constants, hyperfine/superhyperfine coupling interactions of metal and ligand sites, and local/global zero-field splitting parameters. If multiple Cu(II) centers are involved, as in the trinuclear site of multicopper oxidases and the tetranuclear CuZ site of N2O reductase, the magnetic interactions and associated spectroscopic behavior can become complex so that a unique assignment of electronic structure may require quantum chemical mapping of structural and spectroscopic features. Single-determinant density functional theory (DFT) methods that are widely applicable often struggle to correctly describe the magnetic interaction between Cu(II) sites, and perform inconsistently in reproducing spindependent observables or predicting non-Heisenberg terms of the spin Hamiltonian. Multireference correlated wave function methods such as Difference-Dedicated Configuration Interaction (DDCI) are more reliable but are limited by their cost to simple, usually dinuclear systems and do not provide access to many spectroscopic observables. Such limitations can be lifted by the Density Matrix Renormalization Group (DMRG), which enables multireference calculations to be conducted with unprecedentedly large active spaces. The project involves a combined experimental and theoretical approach, where the French partners will synthesize and spectroscopically characterize biomimetic multinuclear Cu complexes, including a DFT-based description of their properties using spin-projection methods, while the German partners will develop and apply DMRG-based multireference methods on these synthetic models. A major and novel goal is to establish the applicability of DMRG and novel DMRG based techniques to the magnetism and spectroscopy of multicopper systems. The combination of synthesis, spectroscopy and theory aims to first build the basis for interpreting the electronic structure, magnetism and spectroscopy of multicopper complexes, to apply the proven theoretical methods to models of enzymatic systems in order to understand the properties and function of the bioinorganic sites themselves, and finally to inform the synthesis of improved spectroscopic, and potentially functional, analogues of the biological multicopper sites.