Unconventional Parahydrogen-Induced Hyperpolarization Effects in Chemistry and Catalysis: From Photoreactions to Enzymes.

Nuclear spin hyperpolarization utilizing parahydrogen has the potential for broad applications in chemistry, catalysis, biochemistry, and medicine. This review examines recent chemical and biochemical insights gained using parahydrogen-induced polarization (PHIP). We begin with photoinduced PHIP, which allows the investigation of short-lived and photoactivated catalysis. Next, we review the partially negative line effect, in which distinctive line shape helps to reveal information about rapid exchange with parahydrogen and the role of short-lived catalytic species. The NMR signal enhancement of a single proton in oneH-PHIP is discussed, challenging the underpinning concept of the necessity of pairwise hydrogenation. Furthermore, we examine metal-free PHIP facilitated by frustrated Lewis pair molecular tweezers and radicaloids, demonstrating alternative routes to hydrogenation. Although symmetric molecules incorporating parahydrogen are NMR silent, we showcase methods that reveal hyperpolarized states through post-hydrogenation reactions. We discuss chemical exchange processes that mediate polarization transfer between parahydrogen and a molecular target, expanding the reach of PHIP without synthesizing specialized precursors. We conclude this review by highlighting the role of PHIP in uncovering the H activation mechanisms of hydrogenases. By providing a detailed review of these diverse phenomena, we aim to familiarize the reader with the versatility of PHIP and its potential applications for mechanistic studies and chemical analysis.