15 Scientific Article The Israel Chemist and Chemical Engineer Issue 9 · January 2023 · Tevet 5783 Novel molecular architectures for “multicolor” magnetic resonance imaging Amnon Bar-Shir Department of Molecular Chemistry and Materials Science, Weizmann Institute of Science, Rehovot, 7610001, Israel Email: firstname.lastname@example.org 1. Introduction The complexity of biological processes, as well as their tightly controlled regulation, attracts researchers from a wide range of scientific fields. Such multiplexity is apparent in almost every aspect of life, in health and in disease, from enzymatic activity to protein-protein interactions, frommetal ion homeostasis to cell function, from gene expression to neuronal activity, or from gene networks to disease onset and therapeutics mechanisms. Although our accumulated knowledge allows us to understand many aspects of these processes, some are still elusive, unknown, or cannot be studied in an intact live organism. In this regard, luminescent sensors (small molecules , proteins , or nanoformulations ) have been the “highlighter pens” of science for decades, since they enable molecules (or cells) of interest to be tagged, enabling mapping of their location, levels, and functions in multiple distinguishable colors. This capability has advanced our ability to reveal the complexity of cellular events, study their tight regulation, and explore a wide range of biological processes concurrently. Perfecting the chemical and optical properties of luminescent materials, in addition to dramatic improvements in microscopy technologies, provide scientists with the ability to visualize multiple biological targets simultaneously within the same imaging frame. However, the light signal source of these materials remains an obstacle when information is desired from the deep tissue of a live subject. MRI, with its unlimited tissue penetration capabilities and ability to combine information from biological targets with high-resolution anatomical images, has become a valuable imaging technology for molecular and cellular imaging. Amnon Bar-Shir earned his BSc (2002) and MSc in chemistry from Tel Aviv University (2004, under Michael Gozin), both magna cum laude. His PhD (2009, under Yoram Cohen) focused on advanced diffusion NMR and MRI to study the structure and function of the central nervous system. As a postdoc at the Johns Hopkins University School of Medicine under Assaf Gilad he developed genetically engineered reporters for MRI. In 2014 he joined the Weizmann Institute, where he created new kinds of biosensors with artificial “multicolor” features for MRI applications. His lab uses synthetic chemistry, nanofabrication, and protein engineering to generate novel molecular formulations, such as small molecules, nanocrystals, supramolecular assemblies and proteins, as MRI sensors of high sensitivity, specificity, and orthogonality. He has used thesemethods for in-vivo molecular and cellular MRI studies for mapping inflammation, multiplexed in-vivo MRI, imaging orthogonal reporter genes, and sensing metal ions. In addition, he used his techniques to study fundamental questions in supramolecular chemistry, including kinetic features of dynamically exchanging molecular systems and control over nanocrystal formation. Amnon’s research achievements were recognized recently by the 2019 Krill Prize, and the 2021 ICS Excellent Young Scientist Prize. Abstract: Luminescent materials with their rich color palettes have revolutionized the field of bioimaging through the ability to distinguish between spectrally resolved colors and, thus, to map the complexity of biological systems. Yet, advanced solutions to overcome the restricted tissue penetration of light are still needed to allow in vivo mapping of tissue multiplexity in both health and disease. Among the diverse capabilities and many advantages of MRI, the ability to encode specific frequencies of imaging agents and, by that, to allow pseudo-color display of MRI maps, is unique. Here, I summarize our recently developed molecular probes that are capable of generating artificial MR-based colors. To this end, the use of nanofabrication, supramolecular chemistry, and protein engineering approaches to generate novel molecular formulations (inorganic nanocrystals, supramolecular assemblies, and enzyme/substrate pairs) as MRI sensors with uniquemulticolor display characteristics is reviewed.