About

Patrick Holland is the Conkey P. Whitehead Professor of Chemistry at Yale University. His research focuses on compounds containing inexpensive metals such as iron and cobalt, with the aim of understanding their reactions in detail and increasing their potential for use in catalysis. His group prepares highly reactive molecules, including those with weak metal-ligand multiple bonds and open reactive sites, to study their mechanisms and applications. A significant part of his research addresses nitrogen fixation, utilizing atmospheric nitrogen as a resource, with relevance to sustainable fertilizer production and understanding natural enzymes that convert nitrogen into ammonia. His work also explores converting atmospheric nitrogen into organic compounds, producing fuel from solar energy, enzymes with carbon dioxide-reducing active sites, and catalytic functionalizations of alkenes. Recognized as a leader in organometallic mechanisms, Professor Holland has edited a volume of Comprehensive Organometallic Chemistry IV and provides interdisciplinary training in synthesis, inorganic chemistry, organometallic chemistry, mechanistic techniques, and spectroscopy.

Research topics

• Chemistry
• Organic chemistry
• Photochemistry
• Computational chemistry
• Engineering
• Process engineering
• Inorganic chemistry
• Waste management
• Environmental science
• Combinatorial chemistry

Selected publications

• Nickel(I) in an All-Ferric NiFeS Cluster

  ChemRxiv · 2026-05-10

  articleOpen accessSenior author

  Anaerobic carbon monoxide dehydrogenase (CODH) enzymes interconvert CO 2 and CO under mild conditions and with near perfect selectivity. The CODH active site, termed the C-cluster, is a [NiFe 3 S 4 ]-Fe u cluster that can reside in several different oxidation states. Despite decades of research, the electronic structure of the C-cluster remains unresolved and the metal oxidation states are ambiguous. In this study, we interrogate a series of synthetic clusters with [NiFe 3 S 4 ] 3+/2+/1+ cores in multiple oxidation states as models of the C-cluster cubane core. Each cluster is characterized using crystallography, spectroscopy, magnetism, and computations. The most oxidized cluster, [NiFe 3 S 4 ] 3+ , is best described as having Ni 2+ and three Fe 3+ sites. Remarkably, Xray absorption spectroscopy (XAS) data show that reduction to the [NiFe 3 S 4 ] 2+ state results in reduction of nickel to Ni 1+ , even though nearby Fe 3+ sites are present. The fully oxidized Fe 3 +3 subsite can be reduced only after nickel has reached the Ni 1+ state. These results demonstrate that Ni 1+ is a readily accessible oxidation state in FeS clusters topologically relevant to the CODH Ccluster.

  PublisherDOI

• Bypassing the Nitrido Wall Using a Redox‐Active Isocyanide: Nucleophilic Attack on CO by a Rhenium Nitride Complex

  Angewandte Chemie International Edition · 2025-06-04 · 3 citations

  articleSenior authorCorresponding

  Abstract Reactive rhenium(III) nitride complexes could result from filling Re─N π* orbitals, but such complexes lie beyond the “nitrido wall” and are rare due to their instability. Here, we describe a method for bypassing the nitrido wall by incorporating a redox‐active isocyanide supporting ligand, which accommodates two electrons as shown by crystallographic, spectroscopic, and computational studies. These electrons can be returned to the metal during its facile reaction with CO to form a cyanate complex, demonstrating the nucleophilic reactivity of the nitride. Thus, assistance by the isocyanide enables an N 2 ‐derived rhenium nitride to engage in N─C bond forming reactivity.

  PublisherDOI

• Author response for "Integrating Salen Complexes into Gas Diffusion Electrodes for CO2 Electroreduction: Considerations for Employing Molecular Precatalysts in Heterogeneous Electrolyzers"

  2025-09-21

  peer-review
  PublisherDOI

• Alkali Metal Control of Triplet-Mediated C–H Activation in Iron-Mediated Coupling of Dinitrogen and Benzene

  Inorganic Chemistry · 2025-08-20 · 3 citations

  articleCorresponding

  Direct coupling of N2 with abundant feedstocks like benzene to form N-containing organic compounds is a promising strategy for N2 fixation pathways. The challenge of coupling N2 activation and C–H bond oxidative addition was recently solved by introducing a reversible benzene C–H bond activation process mediated by a low-valent Fe(0) complex, which gave an organometallic product that could couple with partially reduced N2. Interestingly, the energetics of the C–H oxidative addition/reductive elimination step depends on the choice of alkali metal. However, the reason why the alkali metal influences the C–H bond activation remained elusive. Herein, we present a comprehensive study on this Fe(0)-mediated reversible C–H activation. Through density functional theory combined with high-level coupled cluster calculations, we discovered that the intermediate-spin triplet (S = 1) controls the energy of the transition state for C–H cleavage, while the high-spin quintet (S = 2) controls the position of the equilibrium. Na+ drives the equilibrium toward oxidative addition due to an electrostatic effect, while K+ and Rb+ are dominated by a steric effect that favors the iron(0) species. The key role played by nonbonding interactions in the Fe-mediated C–H activation provides a conceptual model for alkali control over organometallic transformations.

  PublisherDOI

• Bypassing the Nitrido Wall Using a Redox‐Active Isocyanide: Nucleophilic Attack on CO by a Rhenium Nitride Complex

  Angewandte Chemie · 2025-06-04

  articleSenior authorCorresponding

  Abstract Reactive rhenium(III) nitride complexes could result from filling Re─N π* orbitals, but such complexes lie beyond the “nitrido wall” and are rare due to their instability. Here, we describe a method for bypassing the nitrido wall by incorporating a redox‐active isocyanide supporting ligand, which accommodates two electrons as shown by crystallographic, spectroscopic, and computational studies. These electrons can be returned to the metal during its facile reaction with CO to form a cyanate complex, demonstrating the nucleophilic reactivity of the nitride. Thus, assistance by the isocyanide enables an N 2 ‐derived rhenium nitride to engage in N─C bond forming reactivity.

  PublisherDOI

• A clinical-stage oncology compound selectively targets drug-resistant cancers

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-30

  preprintOpen access

  Re-evaluating existing clinical compounds can uncover previously unrecognized mechanisms that reshape a drug's therapeutic potential. The small molecule Procaspase-Activating Compound 1 (PAC-1) entered oncology testing as a proposed activator of caspase-driven apoptosis. Here, we show that PAC-1-driven cytotoxicity occurs in the absence of executioner caspase expression, demonstrating that its anti-cancer activity occurs via an alternative mechanism. We provide genetic, biochemical, and biophysical evidence demonstrating that PAC-1 functions as a highly selective iron chelator that eliminates cancer cells by disrupting iron homeostasis. Unexpectedly, we discovered that expression of the key chemotherapy-resistance pump MDR1 confers marked hypersensitivity to PAC-1 treatment. While PAC-1 is only weakly effluxed by MDR1 under basal conditions, this process is potentiated when PAC-1 is bound to iron. Consequently, PAC-1 induces progressive iron depletion and selective cytotoxicity in otherwise drug-resistant MDR1-expressing cancer cells. Together, these findings redefine PAC-1's mechanism-of-action and establish a framework for exploiting multidrug resistance as a therapeutic vulnerability through targeted iron starvation.

  PublisherDOI

• Isocyanide Ligation Enables Electrochemical Ammonia Formation in a Synthetic Cycle for N2 Fixation

  UNC Libraries · 2025-11-27

  articleOpen access

  Transition-metal-mediated splitting of N₂ to form metal nitride complexes could constitute a key step in electrocatalytic nitrogen fixation, if these nitrides can be electrochemically reduced to ammonia under mild conditions. The envisioned nitrogen fixation cycle involves several steps: N₂ binding to form a dinuclear end-on bridging complex with appropriate electronic structure to cleave the N₂ bridge followed by proton/electron transfer to release ammonia and bind another molecule of N₂. The nitride reduction and N₂ splitting steps in this cycle have differing electronic demands that a catalyst must satisfy. Rhenium systems have had limited success in meeting these demands, and studying them offers an opportunity to learn strategies for modulating reactivity. Here, we report a rhenium system in which the pincer supporting ligand is supplemented by an isocyanide ligand that can accept electron density, facilitating reduction and enabling the protonation/reduction of the nitride to ammonia under mild electrochemical conditions. The incorporation of isocyanide raises the N-H bond dissociation free energy of the first N-H bond by 10 kcal/mol, breaking the usual compensation between p<em>K</em>_a and redox potential; this is attributed to the separation of the protonation site (nitride) and the reduction site (delocalized between Re and isocyanide). Ammonia evolution is accompanied by formation of a terminal N₂ complex, which can be oxidized to yield bridging N₂ complexes including a rare mixed-valent complex. These rhenium species define the steps in a synthetic cycle that converts N₂ to NH₃ through an electrochemical N₂ splitting pathway, and show the utility of a second, tunable supporting ligand for enhancing nitride reactivity.

  PublisherDOI

• Prospects for forming C–N bonds from dinitrogen

  ChemRxiv · 2025-09-24

  articleOpen accessSenior author

  The formation of C–N bonds from molecular dinitrogen (N2) offers a synthetic route to value-added nitrogen-containing compounds without relying on pre-functionalized nitrogen sources. This Perspective highlights recent advances in forming C–N bonds from N2 with homogeneous transition metal complexes. After discussing how transition metal complexes activate N2 through various coordination modes, we focus on the reactivity of reduced nitrogen intermediates with different kinds of carbon sources. Carbon electrophiles and nucleophiles enable C–N bond formation via insertion, substitution, or radical pathways. Cycloaddition reactions, particularly involving polarized N2 ligands and unsaturated carbon electrophiles, offer routes to more complex products. We describe efforts to achieve catalytic turnover and emphasize the remaining obstacles to catalytic C–N bond construction.

  PublisherDOI

• Illuminating the mechanistic impacts of an Fe-quaterpyridine functionalized crystalline poly(triazine imide) semiconductor for photocatalytic CO ₂ reduction

  Inorganic Chemistry Frontiers · 2025-01-01 · 2 citations

  articleOpen access

  Attachment of a Fe-quaterpyridine catalyst to carbon nitride produces a photocatalyst that selectively reduces CO 2 to CO in water.

  PublisherOA PDFDOI

• Water-Soluble Rhenium Nitride Complexes Supported by Multidentate Phosphinite Ligands Provide Insights into Aqueous Ammonium Synthesis Using Samarium Diiodide

  Inorganic Chemistry · 2025-10-14

  article

  fixation.

  PublisherDOI

Recent grants

• Mechanistically guided improvement in radical alkene coupling by base metal catalysts

  NIH · $1.2M · 2019–2024

• Low-Coordinate Synthetic Models for Iron-Sulfur Enzymes

  NIH · $6.4M · 2004–2027

• SusCHEM: Catalytic Alkene Transformations Using High-Spin Cobalt Complexes

  NSF · $500k · 2015–2019

• Nitrene Transfer Reactions with Iron Complexes

  NSF · $430k · 2009–2013

• Collaborative Research: CAS: Electrochemical Approaches to Sustainable Dinitrogen Fixation

  NSF · $321k · 2020–2023

Frequent coauthors

• William W. Brennessel

  University of Rochester

  247 shared

• Brandon Q. Mercado

  Yale University

  243 shared

• Eckhard Bill

  Max Planck Institute for Chemical Energy Conversion

  154 shared

• R.J. Lachicotte

  150 shared

• Thomas R. Cundari

  University of North Texas

  134 shared

• C.J. Flaschenriem

  112 shared

• William B. Tolman

  Washington University in St. Louis

  106 shared

• Jeremy M. Smith

  Indiana University Bloomington

  104 shared

Education

• PhD, Chemistry

  University of California

  1997

• A. B., Chemistry

  Princeton University

  1993

Awards & honors

• NSF CAREER Award (2002)
• Sloan Fellowship (2003)
• Fulbright Scholar (2012)
• Blavatnik Award for Young Scientists (2013)
• Fellow of the AAAS (2014)