Engineering ruthenium-based organometallic complexes for biological applications

由于广泛的配位数和几何形状，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，金属基配合物是一类特殊的化合物，其与生物分子的反应性与简单的有机分子非常不同。在过去的几年里，我们的研究小组旨在更好地了解金属基复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。我们对基于铼的有机金属配合物的研究特别感兴趣，这是由于它们具有优异的生物和催化活性，而且还由于它们可以容易地进行微调，允许在其结构内引入不同的靶向/细胞穿透剂，产生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。根据我们最近的研究结果，未来5年拟议研究计划的总体目标（将培养3名博士，4名硕士和5名UG学生）分为两个主题。 主题A.我们最近发现，一些硼酸盐抗衡离子，通常被发现作为一个整合的一部分，结构的铼为基础的有机金属配合物确实发挥了重要作用，在其生物活性（因此可能发挥作用，在他们的能力进入人体细胞）。我们的主要目标之一将是阐明这些硼酸盐抗衡离子的生物/催化活性的钌基有机金属配合物的基本作用。 主题B。我们最近也非常感兴趣，在获得更深入的基本了解的行为的温度响应性连接，如呋喃-马来酰亚胺狄尔斯-阿尔德环加成在生物环境（并取得了很大的进展），使用它们作为一种工具，提供基于金属有机配合物的人/细菌细胞内，并提高其细胞内的生物/催化活性。我们的第二个主要目标将是为此目的评价这种联系的潜力。将基于钌等外源金属的络合物的潜力输出到生物竞技场，并研究影响其内化/细胞递送的因素，可能会为代谢干预开辟意想不到的机会，并揭示诊断，成像，催化或治疗的新工具。该研究计划将通过在化学和生物学的界面上提供新的工具，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，无疑将导致与该行业的众多合作，这将有助于我们在研究实验室中的发现找到商业应用的方式，这必将对无数加拿大人和世界各地人民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.