Engineering ruthenium-based organometallic complexes for biological applications

金属络合物具有广泛的配位数和几何构型、可接近的氧化还原状态以及配位配体的热力学/动力学性质和性质，是一类特殊的化合物，它与生物分子的反应活性与简单有机分子有很大的不同。在过去的几年里，我们的研究小组旨在更好地了解金属基络合物在生物环境中的命运，以及影响它们与生物分子相互作用的因素。我们对基于Ru的有机金属配合物的研究特别感兴趣，因为它们具有良好的生物活性和催化活性，而且它们可以很容易地进行微调，允许在其结构中引入不同的靶向/细胞穿透剂，生成具有增强的生物活性和对不同生物靶标的选择性的分子，用于各种应用。根据我们最近的发现，我们提议的未来5年研究计划(将培养3名博士、4名硕士和5名UG学生)的总体目标分为两个主题。主题A.我们最近发现，一些常见的硼酸盐反离子在基于Ru的有机金属配合物的结构中扮演着重要的角色(因此可能在它们进入人体细胞的能力中发挥作用)。我们的主要目标之一将是阐明这些硼酸盐反离子对Ru基有机金属配合物的生物/催化活性的基本作用。最近，我们还非常有兴趣更深入地了解生物环境中温度响应性连接的行为，如呋喃-马来酰亚胺Diels-Alder环加成反应(并取得了很大进展)，将它们用作在人类/细菌细胞内输送基于Ru的有机金属配合物的工具，并增强其细胞内的生物/催化活性。我们的第二个主要目标将是为此目的评估这种联系的潜力。将基于外源金属(如Ru)的络合物的潜力输出到生物领域，并研究影响其内化/细胞递送的因素，可能会为代谢干预打开意想不到的机会，并揭示诊断、成像、催化或治疗方面的新工具。该研究计划将通过在化学和生物界面提供新的工具，对各个工业部门产生积极影响。该项目在位于拉瓦尔“生物技术城”的INRS-AFSB进行，无疑将导致与业界的大量合作，这将帮助我们在研究实验室取得的发现转化为商业应用，这肯定会对无数加拿大人和世界各地的人们的生活产生积极影响。

Because of the wide range of coordination numbers and geometries, accessible redox states, and the thermodynamic/kinetic properties and nature of the coordinating ligands, metal-based complexes are a special class of compounds which display reactivities with biomolecules that are very different than simple organic molecules. In the past years, our research group has aimed at getting a better understanding of the fate of metal-based complexes in biological settings, and the factors that influence their interactions with biomolecules. We have been particularly interested in the study of ruthenium-based organometallic complexes due to their excellent biological and catalytical activities, but also due to the fact that they can easily be fine-tuned, allowing the introduction of different targeting/cell-penetrating agents within their structure, generating molecules with enhanced biological activities and selectivity towards different biological targets for various applications. Based on our recent findings, the general objectives of the proposed research program for the next 5 years (which will train 3 PhD, 4 MSc and 5 UG students) are divided into two themes. Theme A. We recently discovered that some borates counterions that are commonly found as an integrative part of the structure of ruthenium-based organometallic complexes do play an important role in their biological activity (and hence might play a role in their ability to enter human cells). One of our main objectives will be to elucidate the fundamental role of these borate counterions on the biological/catalytical activities of Ru-based organometallic complexes. Theme B. We have also recently been highly interested in getting a deeper fundamental understanding of the behaviour of thermoresponsive linkages such as furan-maleimide Diels-Alder cycloadditions in biological settings (and have made great advances), to use them as a tool to deliver ruthenium-based organometallic complexes within human/bacterial cells, and enhance their intracellular biological/catalytic activities. Our second main objective will then be to evaluate the potential of such linkages for this purpose. Exporting the potential of complexes based on an exogenous metal such as ruthenium to the biological arena and study the factors that have an impact on their internalization/cellular delivery might open unforeseen opportunities for metabolic interventions, and unveil new tools in diagnosis, imaging, catalysis or therapy. This research program will positively impact various industrial sectors by offering novel tools at the interface of chemistry and biology. Undertaken at INRS-AFSB, located in Laval's "Biotech City", this project will undoubtedly lead to numerous collaborations with the industry, which will help the discoveries we make in our research laboratories find their way to commercial applications that will certainly positively impact the lives of countless Canadians and people worldwide.