About

Alexander Angerhofer is a professor in the Department of Chemistry at the University of Florida. His research focuses on the application of electron paramagnetic resonance to study metalloenzymes, specifically investigating the catalytic mechanisms of the manganese-containing enzyme oxalate decarboxylase. His work aims to elucidate the role of the enzyme’s quaternary structure and employs spectroscopic and structural methods, including site-directed mutagenesis with unnatural amino acids, to understand long-range electron transfer between manganese ions within the enzyme. Additionally, he utilizes chemical, molecular biology, and bioinformatics tools to enhance enzyme performance at physiological pH for applications in medicine and food science. Angerhofer has a distinguished academic background, including a Ph.D. in Physics from Universität Stuttgart, a postdoctoral fellowship at Argonne National Laboratory, and habilitation from Universität Stuttgart. His contributions to the field have been recognized with awards such as the NSF in 2020, and he has served as Associate Chair of the Department of Chemistry at the University of Florida.

Research topics

• Crystallography
• Chemistry
• Physics
• Nanotechnology
• Materials science
• Engineering
• Atomic physics
• Photochemistry
• Quantum mechanics
• Inorganic chemistry
• Organic chemistry
• Nuclear magnetic resonance
• Optics
• Optoelectronics
• Chemical engineering
• Physical chemistry
• Chemical physics
• Electrical engineering

Selected publications

• Hopping‐Type Charge Transport in Controllably <i>p</i> ‐Doped Polaronic Two‐Dimensional Polymers

  Angewandte Chemie · 2025-04-14 · 1 citations

  article

  Abstract In this work, we find that controllable p ‐type doping leads to Holstein‐type polarons in four electron‐rich two‐dimensional polymers (2DPs). Substoichometrically injecting holes into these 2DPs leads to small optical bandgaps (&lt;1.0 eV) and electrical conductivities (17 mS m −1 ) significantly higher than their undoped analogs. Fourier‐transform infrared spectroscopy and continuous‐wave electron paramagnetic resonance spectroscopy both reveal that this arises from the formation of paramagnetic polarons. We achieve maximal conductivities when 2DPs comprised of electron‐rich nodes and electron‐rich linkers are combined, which is a consequence of more delocalized polarons as unveiled by diffuse‐reflectance UV–vis‐NIR spectroscopy. Variable‐temperature electrical conductivity measurements reveal two distinct Arrhenius regimes in all 2DPs investigated, which we attribute to the different thermally activated processes inherent to in‐plane and cross‐plane electronic transport in stacked 2DP multilayers. This resulted in a maximum electronic conductivity of 326 mS m −1 at an elevated temperature. Collectively, this report provides fundamental insight into polaron‐based charge‐transport in p ‐type 2D organic layers, which we expect will form the foundation for the eventual deployment of these materials in electronic devices.

  PublisherDOI

• Hopping‐Type Charge Transport in Controllably <i>p</i> ‐Doped Polaronic Two‐Dimensional Polymers

  Angewandte Chemie International Edition · 2025-04-14 · 1 citations

  articleOpen access

  Abstract In this work, we find that controllable p ‐type doping leads to Holstein‐type polarons in four electron‐rich two‐dimensional polymers (2DPs). Substoichometrically injecting holes into these 2DPs leads to small optical bandgaps (&lt;1.0 eV) and electrical conductivities (17 mS m −1 ) significantly higher than their undoped analogs. Fourier‐transform infrared spectroscopy and continuous‐wave electron paramagnetic resonance spectroscopy both reveal that this arises from the formation of paramagnetic polarons. We achieve maximal conductivities when 2DPs comprised of electron‐rich nodes and electron‐rich linkers are combined, which is a consequence of more delocalized polarons as unveiled by diffuse‐reflectance UV–vis‐NIR spectroscopy. Variable‐temperature electrical conductivity measurements reveal two distinct Arrhenius regimes in all 2DPs investigated, which we attribute to the different thermally activated processes inherent to in‐plane and cross‐plane electronic transport in stacked 2DP multilayers. This resulted in a maximum electronic conductivity of 326 mS m −1 at an elevated temperature. Collectively, this report provides fundamental insight into polaron‐based charge‐transport in p ‐type 2D organic layers, which we expect will form the foundation for the eventual deployment of these materials in electronic devices.

  PublisherOA PDFDOI

• Gallic Acid-Encapsulated PAMAM Dendrimers as an Antioxidant Delivery System for Controlled Release and Reduced Cytotoxicity against ARPE-19 Cells

  Bioconjugate Chemistry · 2024-12-06 · 7 citations

  articleOpen access

  Poly(amidoamine) (PAMAM) dendrimers have gained significant attention in various research fields, particularly in medicinal compound delivery. Their versatility lies in their ability to conjugate with functional molecules on their surfaces and encapsulate small molecules, making them suitable for diverse applications. Gallic acid is a potent antioxidant compound that has garnered considerable interest in recent years. Our research aims to investigate if the gallic acid-encapsulated PAMAM dendrimer generations 4 (G4(OH)-Ga) and 5 (G5(OH)-Ga) could enhance radical scavenging, which could potentially slow down the progression of age-related macular degeneration (AMD). Encapsulation of gallic acid in PAMAM dendrimers is a feasible alternative to prevent its degradation and toxicity. In vitro investigation of antioxidant activity was carried out using the DPPH and ABTS radical scavenging assays, as well as the FRAP assay. The IC50 values for DPPH and ABTS assays were determined through nonlinear dose–response curves, correlating the inhibition percentage with the concentration (μg/mL) of the sample and the concentration (μM) of gallic acid within each sample. G4(OH)-Ga and G5(OH)-Ga possess significant antioxidant activities as determined by the DPPH, ABTS, and FRAP assays. Moreover, gallic acid-encapsulated PAMAM dendrimers inhibit H2O2-induced reactive oxygen species (ROS) production in the human retinal pigment epithelium ARPE-19 cells, thereby improving antioxidant characteristics and potentially retarding AMD progression caused by ROS. In an evaluation of cell viability of ARPE-19 cells using the MTT assay, G4(OH)-Ga was found to reduce cytotoxic effects on ARPE-19 cells.

  PublisherDOI

• Bidentate Substrate Binding Mode in Oxalate Decarboxylase

  Molecules · 2024-09-17 · 1 citations

  articleOpen accessSenior author

  Oxalate decarboxylase is an Mn- and O2-dependent enzyme in the bicupin superfamily that catalyzes the redox-neutral disproportionation of the oxalate monoanion to form carbon dioxide and formate. Its best-studied isozyme is from Bacillus subtilis where it is stress-induced under low pH conditions. Current mechanistic schemes assume a monodentate binding mode of the substrate to the N-terminal active site Mn ion to make space for a presumed O2 molecule, despite the fact that oxalate generally prefers to bind bidentate to Mn. We report on X-band 13C-electron nuclear double resonance (ENDOR) experiments on 13C-labeled oxalate bound to the active-site Mn(II) in wild-type oxalate decarboxylase at high pH, the catalytically impaired W96F mutant enzyme at low pH, and Mn(II) in aqueous solution. The ENDOR spectra of these samples are practically identical, which shows that the substrate binds bidentate (κO, κO’) to the active site Mn(II) ion. Domain-based local pair natural orbital coupled cluster singles and doubles (DLPNO-CCSD) calculations of the expected 13C hyperfine coupling constants for bidentate bound oxalate predict ENDOR spectra in good agreement with the experiment, supporting bidentate bound substrate. Geometry optimization of a substrate-bound minimal active site model by density functional theory shows two possible substrate coordination geometries, bidentate and monodentate. The bidentate structure is energetically preferred by ~4.7 kcal/mol. Our results revise a long-standing hypothesis regarding substrate binding in the enzyme and suggest that dioxygen does not bind to the active site Mn ion after substrate binds. The results are in agreement with our recent mechanistic hypothesis of substrate activation via a long-range electron transfer process involving the C-terminal Mn ion.

  PublisherOA PDFDOI

• Coaxially Conductive Organic Wires Through Self-Assembly

  Journal of the American Chemical Society · 2023-02-28 · 23 citations

  article

  Here, we describe the synthesis of the hexameric macrocyclic aniline (MA[6]), which spontaneously assembles into coaxially conductive organic wires in its oxidized and acidified emeraldine salt (ES) form. Electrical measurements reveal that ES-MA[6] exhibits high electrical conductivity (7.5 × 10–2 S·cm–1) and that this conductivity is acid–base responsive. Single-crystal X-ray crystallography reveals that ES-MA[6] assembles into well-defined trimeric units that then stack into nanotubes with regular channels, providing a potential route to synthetic nanotubes that are leveraged for ion or small molecule transport. Ultraviolet–visible–near-infrared absorbance spectroscopy and electron paramagnetic spectroscopy showcase the interconversion between acidic (conductive) and basic (insulating) forms of these macrocycles and how charge carriers are formed through protonation, giving rise to the experimentally observed high electrical conductivity.

  PublisherDOI

• CCDC 2219209: Experimental Crystal Structure Determination

  The Cambridge Structural Database · 2023-03-01

  datasetOpen access

  An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  PublisherDOI

• Elucidating the Origin of Plasmon-Generated Hot Holes in Water Oxidation

  ACS Nano · 2023-04-13 · 31 citations

  article

  Plasmon-generated hot electrons in metal/oxide heterostructures have been used extensively for driving photochemistry. However, little is known about the origin of plasmon-generated hot holes in promoting photochemical reactions. Herein, we discover that, during the nonradiative plasmon decay, the interband excitation rather than the intraband excitation generates energetic hot holes that enable to drive the water oxidation at the Au/TiO2 interface. Distinct from lukewarm holes via the intraband excitation that only remain on Au, hot holes from the interband excitation are found to be transferred from Au into TiO2 and stabilized by surface oxygen atoms on TiO2, making them available to oxidize adsorbed water molecules. Taken together, our studies provide spectroscopic evidence to clarify the photophysical process for exciting plasmon-generated hot holes, unravel their atomic-level accumulation sites to maintain the strong oxidizing power in metal/oxide heterostructures, and affirm their crucial functions in governing photocatalytic oxidation reactions.

  PublisherDOI

• The absence of the queuosine tRNA modification leads to pleiotropic phenotypes revealing perturbations of metal and oxidative stress homeostasis in <i>Escherichia coli</i> K12

  Metallomics · 2022-01-01 · 33 citations

  articleOpen access

  Queuosine (Q) is a conserved hypermodification of the wobble base of tRNA containing GUN anticodons but the physiological consequences of Q deficiency are poorly understood in bacteria. This work combines transcriptomic, proteomic and physiological studies to characterize a Q-deficient Escherichia coli K12 MG1655 mutant. The absence of Q led to an increased resistance to nickel and cobalt, and to an increased sensitivity to cadmium, compared to the wild-type (WT) strain. Transcriptomic analysis of the WT and Q-deficient strains, grown in the presence and absence of nickel, revealed that the nickel transporter genes (nikABCDE) are downregulated in the Q- mutant, even when nickel is not added. This mutant is therefore primed to resist to high nickel levels. Downstream analysis of the transcriptomic data suggested that the absence of Q triggers an atypical oxidative stress response, confirmed by the detection of slightly elevated reactive oxygen species (ROS) levels in the mutant, increased sensitivity to hydrogen peroxide and paraquat, and a subtle growth phenotype in a strain prone to accumulation of ROS.

  PublisherOA PDFDOI

• Kinetics and basic understanding: general discussion

  Faraday Discussions · 2022-12-15 · 6 citations

  article1st authorCorresponding

  Robert W. Carpick opened a discussion of the paper by Lars Borchardt: For your contact angle measurements, did you measure the surface of the Pd ball, or a flat Pd reference sample? Lars Borchardt replied: We measured on both geometries – the Pd ball and a flat steel substrate th

  PublisherDOI

• Selective incorporation of 5‐hydroxytryptophan blocks long range electron transfer in oxalate decarboxylase

  Protein Science · 2022-12-09 · 3 citations

  articleOpen accessSenior authorCorresponding

  Oxalate decarboxylase from Bacillus subtilis is a binuclear Mn-dependent acid stress response enzyme that converts the mono-anion of oxalic acid into formate and carbon dioxide in a redox neutral unimolecular disproportionation reaction. A π-stacked tryptophan dimer, W96 and W274, at the interface between two monomer subunits facilitates long-range electron transfer between the two Mn ions and plays an important role in the catalytic mechanism. Substitution of W96 with the unnatural amino acid 5-hydroxytryptophan leads to a persistent EPR signal which can be traced back to the neutral radical of 5-hydroxytryptophan with its hydroxyl proton removed. 5-Hydroxytryptophan acts as a hole sink preventing the formation of Mn(III) at the N-terminal active site and strongly suppresses enzymatic activity. The lower boundary of the standard reduction potential for the active site Mn(II)/Mn(III) couple can therefore be estimated as 740 mV against the normal hydrogen electrode at pH 4, the pH of maximum catalytic efficiency. Our results support the catalytic importance of long-range electron transfer in oxalate decarboxylase while at the same time highlighting the utility of unnatural amino acid incorporation and specifically the use of 5-hydroxytryptophan as an energetic sink for hole hopping to probe electron transfer in redox proteins.

  PublisherOA PDFDOI

Recent grants

• Enzymatic Mechanism of Oxalate Decarboxylase Revealed by Biophysical and Structural Studies

  NSF · $473k · 2020–2024

• The Catalytic Mechanism of Oxalate Decarboxylase Studied by Advanced EPR Experiments

  NSF · $476k · 2008–2012

• The Catalytic Mechanism of Oxalate Decarboxylase Studied by Advanced EPR Techniques

  NSF · $430k · 2012–2016

Frequent coauthors

• Peter J. Bratt

  78 shared

• Louis‐Claude Brunel

  70 shared

• J. Krzystek

  National High Magnetic Field Laboratory

  45 shared

• Martin Rohrer

  Bayer (Germany)

  41 shared

• Gail E. Fanucci

  University of Florida

  38 shared

• Christopher P. Jaroniec

  The Ohio State University

  36 shared

• Karen A. Hyde

  Université Claude Bernard Lyon 1

  36 shared

• Gary J. Gerfen

  Albert Einstein College of Medicine

  36 shared

Awards & honors

• NSF (2020)