About

Robert Waymouth is the Robert Eckles Swain Professor of Chemistry and also holds a courtesy appointment in Chemical Engineering at Stanford University. His research focuses on developing new catalytic strategies to create useful molecules, including bioactive polymers, synthetic fuels, and sustainable plastics. He has made significant contributions in organometallic catalysis, devising highly selective alcohol oxidation catalysts and developing platforms of organic catalysts and continuous flow reactors to access complex polymer architectures. His group has also pioneered selective organocatalytic strategies for synthesizing functional degradable polymers and oligomers that serve as 'molecular transporters' for gene, drug, and probe delivery into cells and live animals. Notably, his collaborative work with Professor Wender led to the discovery of Charge-Altering Releasable Transporters (CARTs), a new class of synthetic cationic materials effective for RNA delivery and mRNA-based cancer vaccines. Born in 1960 in Warner Robins, Georgia, Waymouth studied chemistry and mathematics at Washington and Lee University, graduating summa cum laude in 1982. He completed his Ph.D. in chemistry at the California Institute of Technology in 1987 under Professor R.H. Grubbs, focusing on synthetic and mechanistic organometallic chemistry. His postdoctoral research at ETH Zurich with Professor Piero Pino concentrated on catalytic hydrogenation with chiral metallocene catalysts. He joined Stanford faculty in 1988, becoming a full professor in 1997 and the Swain Professor in 2000. His research applies mechanistic principles to develop new concepts in catalysis, with particular emphasis on organometallic and organic catalysts for complex macromolecular synthesis.

Research topics

• Biology
• Physics
• Computer Science
• Artificial Intelligence
• Engineering
• Nanotechnology
• Biotechnology
• Virology
• Chemical physics
• Organic chemistry
• Chemical engineering
• Immunology
• Thermodynamics
• Medicine
• Meteorology
• Astrobiology
• Chemistry
• Systems engineering

Selected publications

• Electrochemical engineering of a membrane-free electrolyzer for the decarbonized production and circular use of acid and base

  Stanford Digital Repository · 2026-05-19

  dissertationOpen access
  PublisherDOI

• <i>In Vivo</i> mRNA Delivery to the Lung Vascular Endothelium by Dicationic Charge-Altering Releasable Transporters

  Journal of the American Chemical Society · 2025-10-21 · 2 citations

  articleOpen accessSenior authorCorresponding

  Endothelial cells (ECs) comprise the pulmonary vascular bed and play a significant role in health and diseases. Consequently, the EC niche represents an attractive therapeutic target for treating a wide range of pulmonary vascular diseases. We have identified a new class of dicationic charge-altering releasable transporters. These single-component transporters selectively deliver mRNA to the lung upon intravenous administration without the use of a targeting ligand. Significantly, the number and spatial array of cationic charges within the repeating units of the CART polymer are found to control both mRNA delivery efficacy and tissue tropism. High-resolution imaging revealed efficient mRNA delivery to endothelial cells in pulmonary arteries, veins, and capillaries. The selective lung tropism of these new CARTs, coupled with the efficient and tunable synthesis of this new family of CART amphiphiles, represents an enabling platform for research and clinical applications.

  PublisherOA PDFDOI

• The Structure and Morphology of Single-Component Oligomeric RNA Delivery Vectors Derived from Amphiphilic Charge-Altering Releasable Transporters

  ACS Nano · 2025-11-06

  articleSenior authorCorresponding

  Advances in nucleic acid delivery have inspired efforts to mimic the function of natural viruses through the development of self-assemblies capable of gene delivery. RNA assemblies based on amphiphilic polymers are emerging as alternatives to lipid nanoparticles, but the factors that govern the self-assembly of RNA with polymeric amphiphiles are poorly understood. Here, we describe the structure of coacervate nanoparticle assemblies derived from RNA and synthetic cationic polymer amphiphiles based on Charge Altering Releasable Transporters (CARTs). CARTs are effective gene delivery agents derived from block copolymer amphiphiles. Cryogenic electron microscopy and tomography (CryoEM, CryoET), small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) reveal that the self-assembly of RNA with low molar mass (≤10,000 g/mol) CART amphiphiles generates nanoparticles with disordered bicontinuous internal morphologies composed of interpenetrating lipid and aqueous coacervate domains. Systematic variation of the cationic and lipophilic blocks in low molar mass CART amphiphiles demonstrates that both the internal domain spacings (6 to 8 nm) and the order of the resulting bicontinuous CART-RNA assemblies depend on the CART chemical structure and the oligonucleotide cargo (mRNA vs siRNA). Notably, the presence of RNA drives the formation of bicontinuous morphologies. In contrast, CART/RNA assemblies with higher molar mass (≥28,000 g/mol) CART amphiphiles fail to generate bicontinuous assemblies, instead yielding aggregates composed of particles approximately 10 to 20 nm in diameter. This work illuminates the internal morphologies of RNA assemblies with synthetic block copolymer amphiphiles, with implications for the rational design of polymer-based RNA delivery systems.

  PublisherDOI

• Targeting the Pulmonary Vascular Endothelium With Charge Altering Releasable Transporters

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01

  article

  Abstract RATIONALE Dysfunction of the pulmonary vascular endothelium is implicated in a variety of pulmonary diseases, including pulmonary hypertension and acute lung injury. Selective targeting of the pulmonary vascular endothelial cells (VECs) can enhance the ability to study these diseases with precision, and promote the development of lung-specific therapeutics. Genetically targeting VECs can be time-consuming and non-specific, whereas nanoparticle delivery to VECs is dependent on ligand targeting, which may be unreliable in disease states. We present a novel nucleic acid delivery vector in the form of amphipathic oligomers known as Charge Altering Releasable Transporters (CARTs), which demonstrate tunable pulmonary VEC tropism dependent on variations in polymer structure, cationic charges, and degradation. Preliminary data suggest that CARTs derived from Ornithine (Orn-CART) and 2,4-Diaminobutyric acid (DABA-CART) target the pulmonary vasculature. In this experiment, we verify in vivo mRNA delivery with Orn-CART and DABA-CART to pulmonary VECs by harnessing Cre-specific genetic recombination in a murine model. METHODS Cre reporter mice containing loxP-flanked STOP cassettes followed by tdTomato were injected with 5 µg of Orn-CART and DABA-CART containing Cre mRNA, with three mice injected per CART. One uninjected littermate was included as a control. Lungs, heart, spleen, kidneys and spleen were harvested 48 hours after CART injections. Cryosections and vibratome sections of fixed organs were stained using immunohistochemistry and imaged for tdTomato signal under confocal microscopy. Quantification of tdTomato signal was performed by manual counting of positive tdTomato positive cells in the pulmonary artery and pulmonary vein endothelium. Statistical analysis and plotting were performed using R software. RESULTS Both Orn-CART and DABA-CART demonstrate remarkable tropism to the pulmonary VECs compared to other organs. In the lung, Cre-mediated recombination was exclusive to the pulmonary endothelium, with significantly more recombination in the pulmonary capillary VECs compared to pulmonary vein and pulmonary artery VECs. There was limited recombination in the bronchial artery VECs, and no recombination in the pulmonary lymphatic endothelium. DABA-CART was more efficient in Cre-mRNA delivery to the pulmonary VECs than Orn-CART. CONCLUSIONS Orn-CART and DABA-CART demonstrate striking tropism to pulmonary VECs, with DABA-CART being significantly more efficient than Orn-CART. We demonstrate that DABA-CART is able to delivery mRNA to murine pulmonary VECs without significant toxicity, and may be a valuable tool to study the pulmonary vascular endothelium in disease models characterized by endothelial dysfunction. With further studies, delivery of RNA utilizing DABA-CART could alter the landscape of precision drugs and gene-based therapies in pulmonary diseases.

  PublisherDOI

• Coacervation drives morphological diversity of mRNA encapsulating nanoparticles

  The Journal of Chemical Physics · 2025-02-19 · 7 citations

  articleOpen access

  The spatial arrangement of components within an mRNA encapsulating nanoparticle has consequences for its thermal stability, which is a key parameter for therapeutic utility. The mesostructure of mRNA nanoparticles formed with cationic polymers has several distinct putative structures: here, we develop a field theoretic simulation model to compute the phase diagram for amphiphilic block copolymers that balance coacervation and hydrophobicity as driving forces for assembly. We predict several distinct morphologies for the mesostructure of these nanoparticles, depending on salt conditions and hydrophobicity. We compare our predictions with cryogenic-electron microscopy images of mRNA encapsulated by charge altering releasable transporters. In addition, we provide a graphics processing unit-accelerated, open-source codebase for general purpose field theoretic simulations, which we anticipate will be a useful tool for the community.

  PublisherOA PDFDOI

• Bis(cyclopentadienyl) Cobalt

  Encyclopedia of Reagents for Organic Synthesis · 2025-07-01

  otherSenior author

  Abstract image [ 1277‐43‐6 ] C 10 H 10 Co (MW 189.12) InChI = 1S/2C5H5.Co/c2*1‐2‐4‐5‐3‐1;/h2*1‐5H; InChIKey = PXFGMRZPRDJDEK‐UHFFFAOYSA‐N (reducing agent; catalyst; source of other organocobalt complexes and of substituted cyclopentanes or cyclopentadienes) Alternative Name: cobaltocene. Physical Data: mp 173–174 °C; sublimes 40 °C/0.1 mmHg; paramagnetic. Solubility: sol petrol and other common org solvents, but reacts with chlorocarbons and oxidizing agents (e.g. nitromethane). Form Supplied in: black–purple cryst; commercially available; readily synthesized from Co II salts [preferably Co(NH 3 ) 6 Cl 2 ] + CpNa in THF. 1 Handling, Storage, and Precautions: highly air‐ and somewhat moisture‐sensitive and light‐sensitive; indefinitely stable in vacuo or under dry inert atmosphere (N 2 , Ar) in the dark; storage in the cold is recommended; toxic.

  PublisherDOI

• Lyophilized SARS-CoV-2 self-amplifying RNA vaccines for microneedle array patch delivery

  Journal of Controlled Release · 2025-06-09 · 11 citations

  article
  PublisherDOI

• <i>In vivo</i> mRNA delivery to the lung vascular endothelium by dicationic Charge-Altering Releasable Transporters

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-19

  preprintOpen accessSenior authorCorresponding

  Abstract Endothelial cells (EC) comprise the pulmonary vascular bed and play a significant role in health and disease. Consequently, the EC niche represents an attractive therapeutic target for treating a wide range of pulmonary vascular diseases. We have identified a new class of dicationic Charge-Altering Releasable Transporters. These single-component transporters selectively deliver mRNA to the lung upon intravenous administration without the use of a targeting ligand. Significantly, the number and spatial array of cationic charges within the repeating units of the CART polymer are found to control both mRNA delivery efficacy and tissue tropism. High-resolution imaging revealed efficient mRNA delivery to endothelial cells in pulmonary arteries, veins and capillaries. The selective lung tropism of these new CARTs, coupled with the efficient and tunable synthesis of this new family of CART amphiphiles, represents an enabling platform for research and clinical applications.

  PublisherOA PDFDOI

• Toughening Poly(lactic acid) without Compromise – Statistical Copolymerization with a Bioderived Bicyclic Lactone

  Journal of the American Chemical Society · 2025-01-28 · 18 citations

  articleCorresponding

  Poly(lactic acid) (PLA) offers a renewable and degradable alternative to petroleum-based plastic, but its mechanical properties are not ideal for many applications. Herein, we describe the synthesis and polymerization of 2-oxo-3,8-dioxabicyclo[3.2.1]octane (ODO), a bioderived bicyclic lactone, and show that copolymers of l-lactide (LA) with small amounts of ODO have improved mechanical properties over PLA. Homopolymerization of ODO to poly(oxo-3,8-dioxabicyclo[3.2.1]octane) (PODO) is optimized for both solution-phase, organocatalytic and melt-phase, metal-catalyzed conditions. In comparison to the monocyclic analog, ε-caprolactone (CL), ODO has a lower enthalpy of polymerization and faster rate of polymerization. PODO is an amorphous, elastomeric polyester that has a Tg 90 °C higher than poly(ε-caprolactone) (PCL). Statistical copolymerization of LA with small fractions of ODO yields tough and transparent thermoplastics that have over 12× elongation at break compared to native PLA, while maintaining Tg, Young’s modulus (E), and yield strength. Together, these results describe how the incorporation of the tetrahydrofuran ring alters lactone polymerizability and the thermomechanical properties of the homopolymer and copolymer materials.

  PublisherDOI

• Electronic Structure of CpCo(η ⁴ -C ₅ H ₆ ): A Catalytic, Organometallic Hydride Donor

  Inorganic Chemistry · 2025-11-11

  article

  In biological and electrochemical processes, electron and proton carriers direct energy transport and storage in chemical bonds. The metallocene CpCo(η4-C5H6) (CpCo(CpH)) is an organometallic hydride donor that selectively transfers hydrides in a manner analogous to biological hydride transfer agents like NAD(P)H. Hydride transfer from CpCo(CpH) generates cobaltocenium ([Cp2Co]+), which in the presence of mild acids can be electrochemically recycled back to CpCo(CpH) without generating hydrogen. We use Co K-edge X-ray absorption and emission spectroscopy and density functional theory to characterize the electronic structure of CpCo(CpH) and illuminate the origins of these unusual chemical properties. We show that the CpH ligand is a strong π acceptor, resulting in a species with high electron density on H that is poised for hydride delivery. Moreover, H/D isotope exchange experiments and reaction coordinate calculations show that hydride transfer occurs from the CpH site, rather than through the Co center, resulting from unfavorable orbital overlap of a Co-bound hydride intermediate. These electronic properties distinguish CpCo(CpH) from other metal hydride species and give rise to unique electrochemical properties. Using these insights, we compare the behaviors of several metallocene hydride species, to explain how variations in electronic structures lead to different chemical and electrochemical properties.

  PublisherDOI

Recent grants

• New Approaches to Reversible Homogeneous Electrocatalysts

  NSF · $555k · 2016–2019

• Materials from High Molecular Weight Cyclic Polymers: Insights on Properties and Dynamics

  NSF · $353k · 2014–2018

• Can Catalysts Dance? Catalytic Choreography in Olefin Polymerization

  NSF · $567k · 2009–2012

• New Materials to Deliver mRNA: Applications in Cancer Immunotherapy

  NIH · $512k · 2020–2025

• CAS: New Strategies for Electrocatalytic Reactions with Transition-Metal Hydrides

  NSF · $704k · 2021–2024

Frequent coauthors

• James L. Hedrick

  IBM Research - Almaden

  189 shared

• Russell C. Pratt

  Lac Courte Oreilles Ojibwa Community College

  92 shared

• Fredrik Nederberg

  Wilmington University

  74 shared

• Bas G. G. Lohmeijer

  BASF (Germany)

  68 shared

• Andrew P. Dove

  University of Birmingham

  55 shared

• Charles G. Wade

  Durham University

  51 shared

• Paul A. Wender

  Stanford University

  42 shared

• Alice P. Gast

  41 shared

Education

• Ph.D., Chemistry

  California Institute of Technology

  1987

• B.S. Mathematics, B.A. Chemistry

  Washington and Lee University

  1982