About

Richard Y. Liu, Ph.D., is an Assistant Professor in the Department of Chemistry and Chemical Biology at Harvard University. His research focuses on the development of innovative methods in chemistry and chemical biology, contributing to the advancement of the field through his expertise and leadership. Dr. Liu's background includes extensive education and research experience, and he is actively involved in mentoring a diverse group of postdoctoral fellows, graduate students, and undergraduate students, fostering a collaborative environment for scientific discovery.

Research topics

• Organic chemistry
• Combinatorial chemistry
• Chemistry
• Stereochemistry
• Medicinal chemistry

Selected publications

• Carbonylative Aminative Suzuki–Miyaura Coupling: Pd-Catalyzed Synthesis of Amides from Vinyl/Aryl Halides and Boronic Acids

  ChemRxiv · 2026-04-02

  articleOpen accessSenior author

  Amide synthesis is critical for the development of pharmaceuticals, agrochemicals, and functional materials. Here, we report a four-component variant of the Pd-catalyzed Suzuki–Miyaura coupling that repurposes partners conventionally used for C–C bond formation to instead yield amides. The sequential insertion of CO, from Mo(CO)6 as a convenient surrogate, and NH, from O-(diphenylphosphinyl)hydroxylamine (DPPH), allows access to a broad scope of amides, enamides, α,β-unsaturated amides, and α,β-unsaturated enamides. Drug-like analogs can be rapidly assembled, and we show that “reverse amide” counterparts can be generated from the same starting materials.

  PublisherOA PDFDOI

• Organic photochemistry for direct light-driven separations

  Chemical Science · 2026-01-01

  articleOpen accessSenior author

  and selective anion recovery from water. We highlight key design strategies for photo-pH-swing capture and identify current practical limitations toward translating solar-driven separations into technologies with meaningful impact.

  PublisherOA PDFDOI

• Geminal Atom Catalysts with Minimized d-Orbital Holes Enable β-Elimination-Resistant C(sp2)-C(sp3) Cross-Coupling

  National University of Singapore · 2026-04-09

  article

  10.1021/jacs.6c00936

  Publisher

• Abstract LB355: ICP-B794, a B7H3-targeting ADC with a novel linker-payload, demonstrated superior anti-tumor activity and large therapeutic window in preclinical studies

  Cancer Research · 2026-04-17

  article

  Abstract The B7H3-targeted antibody-drug conjugates (ADCs) have shown encouraging clinical efficacy in the treatment of multiple solid tumors. Here, we present a new B7H3-ADC, ICP-B794 created based on a novel linker-payload platform, which was able to overcome the resistant of cancer to DS-7300 in an in vivo xenograft model and exhibited large safety window. The novel ADC linker-payload platform consists of an irreversible connector, a proprietary hydrophilic linker via introducing PEG and a novel highly potent TOPO1 inhibitor payload with low P-gp sensitivity. The B7H3-ADC ICP-B794 based on this novel platform exhibited excellent drug-to-antibody ratio (DAR) value stability and low payload release in human plasma. In the in vitro cellular assays, ICP-B794 demonstrated significantly improved potency than DS-7300. To compare the in vivo anti-tumor efficacy of other B7H3-ADCs with ICP-B794, the linker-payloads from multiple ADC platforms were conjugated to the same B7H3 antibody used in ICP-B794, and the in vivo anti-tumor activities of the resulting ADCs and ICP-B794 were evaluated head-to-head in a xenograft model. ICP-B794 demonstrated superior in vivo efficacy to B7H3-ADCs generated from other platforms in a NCI-H1155 NSCLC xenograft model. The minimum effective dose (MED) of ICP-B794 in the NCI-H1155 CDX model is 0.15 mg/kg. The NCI-H1155 model is resistant to DS-7300 treatment at 10 mg/kg, however, ICP-B794 treatment at 5 mg/kg following treatment of DS-7300 at 10 mg/kg still achieved complete tumor regression, indicating that ICP-B794 overcame the resistance of lung cancer to DS-7300. In the GLP toxicology study in monkeys, ICP-B794 administered via intravenously injection once every 3 weeks for 3 doses exhibited approximate dose-proportional PK and high stability in circulation. The highest non-severely toxic dose (HNSTD) was defined as 10 mg/kg and no interstitial inflammation or other lung toxicities were observed. The safety window of ICP-B794 HNSTD in monkey vs MED in NCI-H1155 model in mice was 267 folds, which is much higher than reported safety window of DS7300 (40 folds calculated based on HNSTD of 30 mg/kg in monkeys vs MED of 3 mg/kg in NCI-H526 model in mice). In summary, ICP-B794 created based on a novel ADC platform exhibited a favorable preclinical profile, including high potency in the in vitro assays, efficacious at very dose level in the in vivo xenograft models, overcoming resistance to DS-7300 and a larger safety window. ICP-B794 is currently being evaluated in a Phase I first-in-human clinical trial (NCT07136558). Citation Format: Dongliang Mo, Yingxiang Gao, Xiaoyan Wang, Yuan Qian, Hongjuan Zhang, Yingrui Han, Richard Liu, Junjian Liu, Charles Wang, Xiangyang Chen, Bin Zhang. ICP-B794, a B7H3-targeting ADC with a novel linker-payload, demonstrated superior anti-tumor activity and large therapeutic window in preclinical studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB355.

  PublisherDOI

• Carbonylative Aminative Suzuki–Miyaura Coupling: Pd-Catalyzed Synthesis of Amides from Vinyl/Aryl Halides and Boronic Acids

  ChemRxiv · 2026-04-01

  articleOpen accessSenior author

  Amide synthesis is critical for the development of pharmaceuticals, agrochemicals, and functional materials. Here, we report a four-component variant of the Pd-catalyzed Suzuki–Miyaura coupling that repurposes partners conventionally used for C–C bond formation to instead yield amides. The sequential insertion of CO, from Mo(CO)6 as a convenient surrogate, and NH, from O-(diphenylphosphinyl)hydroxylamine (DPPH), allows access to a broad scope of amides, enamides, α,β-unsaturated amides, and α,β-unsaturated enamides. Drug-like analogs can be rapidly assembled, and we show that “reverse amide” counterparts can be generated from the same starting materials.

  PublisherDOI

• Author response for "Organic Photochemistry for Directly Light-Driven Separations"

  2026-03-17

  peer-reviewSenior author
  PublisherDOI

• Dual-Ligand System for Mild Decarbonylative Suzuki–Miyaura Cross-Coupling of Aroyl Chlorides

  ACS Catalysis · 2026-03-09

  articleOpen accessSenior authorCorresponding

  Cooperativity between a pair of phosphine ligands enables general Pd-catalyzed decarbonylative Suzuki-Miyaura cross-couplings between (hetero)-aroyl chlorides and (hetero)-arylboronic acids under mild conditions. Experimental and computational studies support a ligand-relay mechanism in which each phosphine preferentially promotes different elementary steps, enhancing the yield and selectivity relative to using either ligand alone. These results validate empirical, mechanism-agnostic screening through pooling-deconvolution as a means for identifying synthetically enabling catalytic methods and mechanisms for multiligand cooperativity.

  PublisherDOI

• Carbenylative Buchwald-Hartwig Coupling of Aryl Halides, N-Tosylhydrazones, and Anilines

  ChemRxiv · 2026-05-04

  articleOpen accessSenior author

  A Pd/Cu cocatalyzed synthesis of N-benzhydryl amines from aryl halides (electrophiles), N-tosylhydrazones (carbene equivalents), and anilines (nucleophiles) has been developed. The reaction operates under mild conditions and exhibits broad substrate scope and excellent functional group tolerance. The synthetic utility of this approach is highlighted by the concise preparation of various drug molecules and their analogues, as well as its integration into downstream derivatizations. The essential role of Cu complexes is unusual for Pd-catalyzed C–N cross-coupling reactions, which usually do not require a cocatalyst for ligand exchange. We propose that this dual catalysis strategy is necessary to control the timing of Pd amido complex formation.

  PublisherOA PDFDOI

• Geminal Atom Catalysts with Minimized d-Orbital Holes Enable β-Elimination-Resistant C(sp ² )–C(sp ³ ) Cross-Coupling

  Journal of the American Chemical Society · 2026-04-09

  article

  Heterogeneous C(sp2)–C(sp3) Suzuki–Miyaura coupling offers an attractive route for the large-scale and sustainable synthesis of structurally complex and pharmaceutically relevant molecules that are otherwise difficult to access. However, the low reactivity of unactivated alkyl electrophiles and the intrinsic instability of alkyl metal intermediates, particularly their propensity for β-hydride elimination, render selective C(sp2)–C(sp3) bond formation exceptionally challenging. Here, we integrate high-throughput density functional theory (DFT) screening with quantum-chemical calculations to identify Cu-based geminal-atom catalysts as optimal candidates and uncover the critical role of d-orbital holes that promote agostic interactions, leading to undesired β-hydride elimination. Guided by these insights, we develope a d-orbital hole passivation strategy to fabricate a class of high-fidelity Cu-based geminal-atom catalysts (HF–Cu/GACs), simultaneously accelerating oxidative addition and suppressing β-hydride elimination, enabling broad-scope and highly selective C(sp2)–C(sp3) cross-coupling between aryl boronic esters and alkyl (pseudo)halides. These catalysts enable the synthesis of diverse pharmaceutically relevant intermediates in fewer steps, with higher yields and using safer, more sustainable conditions compared to traditional routes. Mechanistic studies reveal that the HF–Cu/GACs feature paired, low-valent Cu centers with minimal d-orbital holes, and that C–Br bond activation proceeds through a surface-mediated single-electron transfer between coadsorbed reactants, rather than free-radical rebound pathways. The findings here establish a generalizable strategy for electronic-state engineering of geminal metal sites to overcome long-standing challenges in cross-coupling chemistry and highlight the potential of heterogeneous Cu catalysts for the sustainable synthesis of fine chemicals and pharmaceuticals.

  PublisherDOI

• Author response: Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome

  2025-03-13

  peer-reviewOpen access
  PublisherDOI

Frequent coauthors

• Stephen L. Buchwald

  Massachusetts Institute of Technology

  38 shared

• Chun Fan

  Temple University

  38 shared

• Kenneth S. Zuckerman

  38 shared

• Timothy M. Swager

  Massachusetts Institute of Technology

  36 shared

• Roy Garcia

  32 shared

• Richard Jove

  32 shared

• Shao‐Xiong Lennon Luo

  Massachusetts Institute of Technology

  13 shared

• Michael J. Aziz

  Harvard University

  9 shared

Labs

• R. Liu GroupPI

Education

• Ph.D., Chemistry

  Harvard University

  2002

• B.S., Chemistry

  University of California, Berkeley

  1997