Gas-phase chemistry of biological and metal-containing ions

蛋白质组学的爆炸性和重大进展已经通过生物质谱（MS）的创新技术突破和概念发展成为可能。作为质谱中蛋白质鉴定基础的两个关键技术领域是肽的离子产生和碰撞诱导解离（CID）。我们提出的研究继续旨在更好地了解这些反应和过程的基本原理，以及所产生的离子的结构和能量。 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。 具体地说，我们的目标是探索（i）寡肽的分子自由基阳离子的结构、能量学、形成和碎裂化学;这些离子与中性肽的不同之处在于少一个电子，具有与它们的质子化对应物不同的结构和性质，并且当经受CID诱导的气相微测序时提供独特的信息;和（ii）金属化的肽和三元复合物;金属化赋予肽独特的和令人感兴趣的结构和化学性质。 拟议的调查将进行的实验，包括串联MS，阈值CID测量，红外多光子解离（IRMPD）光谱，和DFT计算的组合。 串联MS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测量将在配有环形离子导向器q2的三重四极杆质谱仪上进行。 所有上述硬件都可以在申请人在约克大学的实验室中获得。 IRMPD光谱实验将在位于荷兰纽韦根的FOM等离子体物理研究所“Rijnhuizen”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.