Gas-phase chemistry of biological and metal-containing ions

生物质谱（MS）的创新技术突破和概念发展使蛋白质组学的爆炸性和重大进展成为可能。离子生成和肽的碰撞诱导解离（CID）是MS中蛋白质鉴定的两个关键技术领域。我们提出的研究继续旨在更好地理解这些反应和过程的基本原理，以及所产生离子的结构和能量学。这些知识对于最终更准确和有效的蛋白质测序和鉴定非常重要，特别是在发现和鉴定疾病生物标志物的应用中。特别是，我们的目标是探索(1)寡肽分子自由基阳离子的结构、能量学、形成和破碎化学；这些离子与中性肽的不同之处在于少了一个电子，具有不同于质子化产物的结构和性质，并且在进行cid诱导的气相微测序时提供独特的信息；（二）金属化肽和三元配合物；金属化赋予多肽独特而有趣的结构和化学性质。所提出的研究将通过一系列实验进行，包括串联质谱、阈值CID测量、红外多光子解离（IRMPD）光谱和DFT计算。串联质谱实验将在原型和/或市售质谱仪上进行，包括三重四极杆、线性离子阱和三维离子阱。阈值CID测量将在装有环形离子导q2的三重四极杆质谱仪上进行。申请人在约克大学的实验室中可以获得上述所有硬件。IRMPD光谱实验将在位于荷兰Nieuwegein的Rijnhuizen等离子体物理研究所的自由电子激光红外实验（FELIX）设施中进行。

Explosive and significant advances in proteomics have been made possible by innovative technological breakthroughs and conceptual developments in biological mass spectrometry (MS). Two key technological areas that are the foundations of protein identification in MS are ion generation and collision-induced dissociation (CID) of peptides. Our proposed research continues to aim at better understanding the fundamentals of these reactions and processes, as well as the structures and energetics of the resulting ions. This knowledge is important for eventually more accurate and efficient protein sequencing and identification, especially in applications to discover and identify disease biomarkers. In particular, our objectives are to explore the structures, energetics, formation, and fragmentation chemistries of (i) molecular radical cations of oligopeptides; these ions differ from the neutral peptides by having one fewer electron, have structures and properties that are different from their protonated counterparts, and provide unique information when subject to CID-induced gas-phase microsequencing; and (ii) metalated peptides and ternary complexes; metalation imparts unique and interesting structures and chemistries to the peptides. The proposed investigations will be carried out by means of a combination of experiments, including tandem MS, threshold CID measurements, infrared multiple photon dissociation (IRMPD) spectroscopy, and DFT calculations. Tandem MS experiments will be conducted on prototype and/or commercially available mass spectrometers, including triple-quadrupole, linear ion trap, and three-dimensional ion trap. Threshold CID measurements will be conducted on a triple-quadrupole mass spectrometer fitted with a ring ion guide as q2. All of the above hardware is available in the applicant's laboratory at York University. IRMPD spectroscopic experiments will be performed in the Free Electron Laser for Infrared Experiments (FELIX) facility at the FOM-Institute for Plasma Physics "Rijnhuizen" in Nieuwegein, the Netherlands.