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

铜活性位点起着重要的生物学作用，包括电子转移、二氧结合、活化和还原以及反硝化过程。酶解铜中心的几何和电子结构极其多样，范围从单核位点到双核、三核和四核簇。当具有磁性活性的Cu（II）离子靠近存在或通过化学键相互作用时，它们的未配对自旋矩偶联导致磁性和光谱学方面的丰富现象学。这主要通过电子顺磁共振（EPR）技术来探测，并通过自旋哈密顿参数（如交换耦合常数、金属与配体位点的超精细/超精细耦合相互作用、局部/全局零场分裂参数）来表达。如果涉及多个Cu（II）中心，如多铜氧化酶的三核位点和N2O还原酶的四核位点，则磁相互作用和相关的光谱行为可能变得复杂，因此可能需要对结构和光谱特征进行量子化学作图来确定唯一的电子结构。广泛应用的单行列式密度泛函理论（DFT）方法往往难以正确描述Cu（II）位点之间的磁相互作用，并且在再现独立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，如差分专用配置相互作用（DDCI）更可靠，但受其成本限制，通常用于简单的双核系统，并且不能提供许多光谱观测值。这种限制可以通过密度矩阵重整化组（DMRG）解除，它可以在前所未有的大活动空间中进行多参考计算。该项目涉及实验和理论相结合的方法，其中法国合作伙伴将合成和光谱表征仿生多核铜配合物，包括使用自旋投影方法对其性质进行基于dft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的新技术在多铜系统的磁性和光谱学中的适用性。合成、光谱学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、磁性和光谱学的基础，将已证实的理论方法应用于酶系统模型，以了解生物无机位点本身的性质和功能，最后为合成改进的光谱和潜在功能的生物多铜位点类似物提供信息。

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.