Junnian Wei

Abstract N-containing organic compounds are of vital importance to lives. Practical synthesis of valuable N-containing organic compounds directly from dinitrogen (N2), not through ammonia (NH3), is a holy-grail in chemistry and chemical industry. An essential step for this transformation is the functionalization of the activated N2 units/ligands to generate N−C bonds. Pioneering works of transition metal-mediated direct conversion of N2 into organic compounds via N−C bond formation at metal-dinitrogen [N2-M] complexes have generated diversified coordination modes and laid the foundation of understanding for the N−C bond formation mechanism. This review summarizes those major achievements and is organized by the coordination modes of the [N2-M] complexes (end-on, side-on, end-on-side-on, etc.) that are involved in the N−C bond formation steps, and each part is arranged in terms of reaction types (N-alkylation, N-acylation, cycloaddition, insertion, etc.) between [N2-M] complexes and carbon-based substrates. Additionally, earlier works on one-pot synthesis of organic compounds from N2 via ill-defined intermediates are also briefed. Although almost all of the syntheses of N-containing organic compounds via direct transformation of N2 so far in the literature are realized in homogeneous stoichiometric thermochemical reaction systems and are discussed here in detail, the sporadically reported syntheses involving photochemical, electrochemical, heterogeneous thermo-catalytic reactions, if any, are also mentioned. This review aims to provide readers with an in-depth understanding of the state-of-the-art and perspectives of future research particularly in direct catalytic and efficient conversion of N2 into N-containing organic compounds under mild conditions, and to stimulate more research efforts to tackle this long-standing and grand scientific challenge.

While immune checkpoint blockade leads to potent antitumor efficacy, it also leads to immune-related adverse events in cancer patients. These toxicities stem from systemic immune activation resulting in inflammation of multiple organs, including the gastrointestinal tract, lung, and endocrine organs. We developed a dual variable domain immunoglobulin of anti-CTLA4 antibody (anti-CTLA4 DVD, where CTLA4 is defined as cytotoxic T lymphocyte-associated antigen-4) possessing an outer tumor-specific antigen-binding site engineered to shield the inner anti-CTLA4-binding domain. Upon reaching the tumor, the outer domain was cleaved by membrane type-serine protease 1 (MT-SP1) present in the tumor microenvironment, leading to enhanced localization of CTLA4 blockade. Anti-CTLA4 DVD markedly reduced multiorgan immune toxicity by preserving tissue-resident Tregs in Rag 1-/- mice that received naive donor CD4+ T cells from WT C57BL/6j mice. Moreover, anti-CTLA4 DVD induced potent antitumor effects by decreasing tumor-infiltrating Tregs and increasing the infiltration of antigen-specific CD8+ T lymphocytes in TRAMP-C2-bearing C57BL/6j mice. Treg depletion was mediated through the antibody-dependent cellular cytotoxicity (ADCC) mechanism, as anti-CTLA4 without the FcγR-binding portion (anti-CTLA4 DANA) spared Tregs, preventing treatment-induced toxicities. In summary, our results demonstrate an approach to anti-CTLA4 blockade that depletes tumor-infiltrating, but not tissue-resident, Tregs, preserving antitumor effects while minimizing toxicity. Thus, our tumor-conditional anti-CTLA4 DVD provides an avenue for uncoupling antitumor efficacy from immunotherapy-induced toxicities.

Switchable catalysts incorporate stimuli-responsive features and allow synthetic tasks that are difficult or impossible to accomplish in other ways. They mimic biological processes in that they can provide both spatial and temporal control, unlike most reactions promoted by human-made catalysts that usually occur according to carefully optimized conditions. In the area of switchable catalysis, redox-switchable ring-opening polymerization (ROP) has attracted much attention, emerging as a powerful strategy for the development of environmentally friendly biodegradable copolymers, especially those containing blocks with complementary properties. Controlling the sequence and regularity of each copolymeric building block can affect the material properties significantly since they are directly related to the respective microstructures. Such control can be exerted with a well-designed redox-switchable catalyst by timing the oxidation and reduction events. In highly selective systems, one form of the catalyst reacts with a monomer until the redox state of the catalyst is altered, at which point the altered state of the catalyst reacts with another monomer. The reaction time may be varied from one cycle to another to generate various designer multiblock copolymers. The first instance of redox-mediated ROP was described by N. Long and co-workers in 2006. This example, as well as many early reported redox-switchable catalysts, could only achieve an on/off switch of activity toward a single monomer or substrate. However, our efforts brought on a general strategy for designing redox-switchable metal complexes that can catalyze different reactions in two oxidation states. In recent years, our contributions to this research field led to the synthesis of several multiblock copolymers prepared from biorenewable resources. This Account provides an overview of reported redox-switchable polymerization catalysts that allow for complementary reactivity in different oxidation states and highlights the potential of this strategy in preparing biodegradable materials. First, we define the field of redox-switchable catalysis and illustrate the design and significance of our ferrocene-chelating ligands, in which the oxidation state of iron in ferrocene can control the reactivity of the resulting metal complexes remotely. Next, we illustrate recent advances in the synthesis of new biodegradable copolymers including (1) how to tune the activity of the ROP catalysts by exploring various metal centers and ferrocene-based ligand combinations; (2) how to synthesize new multiblock copolymers of cyclic esters, epoxides, and carbonates by redox-switchable ROP; and (3) how to understand the mechanism of these reactions by discussing both experimental and theoretical investigations. By the application and development of redox-switchable strategies, various novel materials and reactions can be expected in the future.

Zr-C4 could detect acute changes in tumor expression of PD-L1 due to standard of care chemotherapies. In summary, we present evidence that low levels of PD-L1 in clinically relevant cancer models can be imaged with immunoPET using a novel recombinant human antibody.

Metalloaromatic species are unique and important both experimentally and theoretically. Significant progress has been made during the past few decades. New aromatic systems have challenged and extended the concept of aromaticity remarkably. In this perspective, recent results on the study of the dianion aromatic metalloles and their corresponding analogues are reviewed. These include the dilithio group 14 metalloles, group 13 metalloles and transition metal metalloles. X-ray crystallography has made a key contribution to the understanding of the structures. Various theoretical tools, such as NICS and AdNDP, make it possible to measure the aromaticity beyond Hückel's rule. The dianion butadiene skeletons play a key role in these metalloles and can be regarded as non-innocent ligands, which accept the electrons from the metal center and thus form the aromatic rings. By simply changing the central metals to different metals, the metallole analogues such as dicupra[10]annulenes and spiroaromatic palladoles can also be generated, which opens a door to synthesize other metalla-macrocyclic aromatics. Key challenges and envisioned opportunities for the future, such as applying these dianion metalloles as novel ligands of transition metals and generating new types of organometallic aromatic system, are also discussed.