FACULTY RESEARCH SPOTLIGHT · 2024

Smart Molecules and Smarter Methods: Anzenbacher Group Advances Sensing, Chirality, and Data-Driven Chemistry

Pavel Anzenbacher, Jr., Ph.D.  ·  Director, Center for Photochemical Sciences  ·  Professor of Chemistry  ·  Department of Chemistry & CPS

The challenges that define supramolecular chemistry — building molecules that recognize specific targets with high selectivity, measuring the handedness of compounds with speed and reliability, and understanding how porphyrin architecture shapes photophysical properties — are perennial ones that require constant innovation. In 2024, the Anzenbacher Group at BGSU published three papers that collectively exemplify that innovation, advancing the group's research programs in anion sensing, chirality detection, and porphyrin science simultaneously.

Each paper reflects a different dimension of the group's work: one tackles a fundamental challenge in the detection of biological phosphate in water; one introduces a computational approach to the longstanding problem of measuring how "handed" a chiral molecule is; and one advances the photophysical understanding of the chiral porphyrin macrocycles that the group has been developing in collaboration with Czech colleagues for over a decade.

Three papers in 2024 — each a different tool in the same toolkit: molecules engineered to recognize, to measure, and to illuminate.

01  Seeing Phosphate in a Sea of Anions

Published in: Chemistry — A European Journal, 30(61), e202401872 · November 2024

Authors: D. Ray, A.R. Sartori, A. Radujević, S.M. George, R. Postema, X. Tan, V.S. Bryantsev, P. Anzenbacher Jr.

DOI: 10.1002/chem.202401872

Collaborating Institutions: Oak Ridge National Laboratory, BGSU (Tan Lab)

THE CHALLENGE: SELECTIVITY IN WATER

Orthophosphate — the simplest inorganic phosphate anion, H₂PO₄⁻ — is biologically essential. It is released when cells lyse, when ATP is hydrolyzed, and when phospholipids break down. Detecting it selectively in complex biological media is therefore a valuable capability, with applications ranging from real-time monitoring of cell death to environmental phosphate sensing.

The challenge is daunting: phosphate is structurally similar to many other anions, and water molecules surround all anions with tight hydration shells that competing receptors must overcome to bind their target. Most synthetic receptors that work beautifully in organic solvents fail in water.

THE HYBRID SOLUTION: AZACROWN PLUS CALIXPYRROLE

This paper introduces an azacrown-calixpyrrole hybrid receptor — a molecule that fuses two previously separate receptor families. Calix[4]pyrroles bind anions through directional N–H hydrogen bonds that provide selectivity, but are too weak in water. Polyammonium azacrowns attract anions electrostatically with great strength, but without selectivity. The hybrid takes the best of both: positively charged ammonium groups for electrostatic attraction, and calixpyrrole hydrogen bond donors for directional selectivity, in a single covalently linked framework.

The result is a receptor with remarkable selectivity: it binds orthophosphate (H₂PO₄⁻) strongly and selectively, outcompeting pyrophosphate (H₂P₂O₇²⁻), AMP, and larger phosphate-containing biomolecules including ADP, ATP, cellular polyphosphates, and phospholipids — all in water. The selectivity hierarchy was characterized by NMR and fluorescence titrations, and supported by molecular dynamics and ab initio MD calculations, with the computational work contributed by Vyacheslav Bryantsev's group at Oak Ridge National Laboratory.

A particularly striking demonstration: the receptor was used to monitor cell lysis in real time. When lysozyme digests bacterial cell walls, the lysed cells release orthophosphate into solution. The fluorescent hybrid receptor detected this release in real time — a direct proof-of-concept for biological sensing in a physiologically relevant environment.

Half calixpyrrole, half azacrown — a molecular hybrid that finally gives anion sensing the selectivity it needs to work where biology actually happens.

WHY IT MATTERS

This paper also reflects an important inter-group collaboration within the CPS: graduate student Rick Postema and Dr. Xiaohong Tan contributed aptamer and biochemistry expertise to the biological validation experiments, exemplifying the kind of cross-disciplinary synergy that the Center for Photochemical Sciences was built to support. The result is a receptor-sensor system with real biological utility — and a synthetic strategy that other researchers can adapt for other challenging anion targets in aqueous environments.

02  Predicting Chirality with Data Science

Published in: Chem (Cell Press), 10, 2345–2348 · July 2024

Authors: P. Anzenbacher Jr., A.R. Sartori, A. Radujević, S.M. George

DOI: 10.1016/j.chempr.2024.06.032

THE ENANTIOMERIC EXCESS PROBLEM

In chemistry, enantiomers are mirror-image molecules — identical in every way except for the three-dimensional orientation of their atoms. For many pharmaceuticals, only one enantiomer has the desired therapeutic effect; the other may be inactive or even harmful. Measuring enantiomeric excess (ee) — the degree to which one enantiomer predominates in a mixture — is therefore a fundamental quality control step in pharmaceutical synthesis and asymmetric catalysis.

The Anzenbacher Group has spent years developing fluorescence-based assays for ee determination in chiral amines and amino alcohols — analytes that are both chemically important and technically challenging to measure. The group's previous work established high-throughput optical assays that could screen large numbers of samples quickly. The remaining bottleneck: each assay requires an extensive calibration curve, and generating those curves for every new amine analyte is time-consuming.

ENTER DATA SCIENCE

This paper, published in the prestigious journal Chem, presents a workflow method that uses data science to predict calibration curves rather than measure them experimentally. By training on existing calibration data across a range of chiral amine analytes, the method learns the relationships between molecular structure and sensor response — and can then predict, without running extensive experiments, how a new amine will behave in the assay.

This is a significant practical advance. It converts what was a measurement bottleneck — generate a new calibration curve for every new substrate — into a predictive exercise that requires only modest computational resources and the underlying sensor array data the group already possesses. The workflow makes high-throughput enantiomeric excess determination more accessible and faster, with implications for drug development pipelines where many substrates must be screened.

The calibration curve you didn't have to run: data science replaces hours of experimentation with a prediction — and it works.

03  Chiral Porphyrins: Reading Handedness from Spectroscopy

Published in: Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 316, 124308 · 2024

Authors: T. Navrátilová, F. Králík, M. Havlík, A. Tatar, M. Drozdová, P. Anzenbacher Jr., B. Dolenský

DOI: 10.1016/j.saa.2024.124308

Collaborating Institution: Charles University Prague

The third 2024 paper from the Anzenbacher Lab advances the ongoing Czech collaboration with Prof. Bohumil Dolenský's group at Charles University Prague — a partnership focused on chiral porphyrin macrocycles built on the Tröger's base and spiro-Tröger's base scaffolds.

Porphyrin-Tröger's base and porphyrin-chlorin spiro-Tröger's base derivatives are chiral macrocycles in which enantiomeric pairs (mirror-image molecules) have identical chemical compositions but different three-dimensional shapes. Characterizing how those enantiomers differ spectroscopically — using UV/Vis, circular dichroism (CD), and DFT calculations — is essential for understanding their photophysical properties and for applying them to chiroptical sensing and recognition applications.

This paper presents a systematic spectroscopic study of nickel(II) complexes of both enantiomeric forms of these structures, supported by density functional theory calculations that explain the observed spectral differences at the electronic level. The work provides a detailed map of how chirality manifests in the spectroscopic signatures of these complex porphyrin architectures — groundwork that informs the rational design of the next generation of chiral porphyrin sensors.

A UNIFIED RESEARCH VISION

The Anzenbacher Program: Three Directions, One Mission

Three 2024 papers spanning sensor chemistry, data science, and porphyrin photophysics might seem like a broad portfolio — but they share a common DNA. Each addresses a different aspect of the same central question: how do we design molecules and methods that can detect, measure, and characterize the world at the molecular level with greater precision, selectivity, and efficiency?

The hybrid receptor paper asks: can we make a molecule selective enough to pick out orthophosphate from a biological soup? The data-science paper asks: can we make enantiomeric excess measurement fast enough to keep up with modern synthetic chemistry? The porphyrin paper asks: can we understand the spectroscopic fingerprints of chirality in complex macrocycles well enough to use them as design principles?

Graduate students Austin Sartori, Aco Radujević, Sandra George, and Rick Postema contributed centrally to the 2024 output, alongside colleagues from Oak Ridge National Laboratory and Charles University Prague. As the CPS celebrates 40 years, this blend of synthesis, computation, spectroscopy, and biological application — pursued with long-term international collaborators and talented graduate students — captures the Anzenbacher group's sustained approach to molecular science.

2024 Publications — Anzenbacher Laboratory

Ray, D., Sartori, A.R., Radujević, A., George, S.M., Postema, R., Tan, X., Bryantsev, V.S., & Anzenbacher, P., Jr. (2024). Cellular Phosphate Sensing and Anion Binding by an Azacrown-Calixpyrrole Hybrid. Chemistry — A European Journal, 30(61), e202401872. https://doi.org/10.1002/chem.202401872

Anzenbacher, P., Jr., Sartori, A.R., Radujević, A., & George, S. (2024). Toward Data-Science-Guided Prediction of Enantiomeric Excess in Amines: A Workflow Method. Chem, 10, 2345–2348. https://doi.org/10.1016/j.chempr.2024.06.032

Navrátilová, T., Králík, F., Havlík, M., Tatar, A., Drozdová, M., Anzenbacher, P., Jr., & Dolenský, B. (2024). Spectroscopic Study on Enantiomeric Ni(II) Complexes of Porphyrin-Tröger's Base and Porphyrin-Chlorin Spiro-Tröger's Base Derivatives Supported by DFT Calculations. Spectrochimica Acta Part A, 316, 124308. https://doi.org/10.1016/j.saa.2024.124308

FACULTY RESEARCH SPOTLIGHT · 2024

Nature's Perfect Machine: How Rhodopsin Uses Vibration to Convert Light with Near-Perfect Efficiency

Massimo Olivucci, Ph.D.  ·  Research Professor  ·  Director, Laboratory for Computational Photochemistry and Photobiology  ·  Department of Chemistry & CPS

Vision is one of biology's most efficient processes. When a photon enters the eye and strikes a rhodopsin molecule in a rod cell, the retinal chromophore it carries undergoes a photoisomerization — a light-driven rotation around a specific carbon-carbon double bond — with a quantum efficiency of about 67%. That means roughly two out of every three absorbed photons successfully drive the reaction forward. The remaining one-third is lost to competing pathways.

For a spontaneous photochemical reaction in solution, 67% is extraordinary. Synthetic molecular motors designed to mimic rhodopsin — molecules that rotate in response to light like nanoscale turbines — typically achieve quantum efficiencies of 50% or less. For decades, the gap between natural and synthetic photochemical machines has been clear, but its molecular origin has remained obscure. What exactly does rhodopsin do that synthetic rotors cannot?

A 2024 paper in Nature Communications from Dr. Massimo Olivucci's Laboratory for Computational Photochemistry and Photobiology at BGSU provides the most detailed answer yet — and in doing so, establishes a design principle for building better synthetic molecular motors.

Published in: Nature Communications, 15, 3388 · April 25, 2024

Authors: A. Blanco-González, M. Manathunga, X. Yang, M. Olivucci

DOI: 10.1038/s41467-024-47477-0

Affiliations: BGSU Center for Photochemical Sciences & Department of Chemistry; University of Siena, Italy; Michigan State University

THE QUESTION: WHY IS RHODOPSIN SO EFFICIENT?

The study uses quantum-classical trajectory simulations — the same high-level computational methodology that has been a hallmark of the Olivucci group's research for decades — to directly compare the excited-state dynamics of two systems: rhodopsin itself, and a synthetic biomimetic molecular rotor called MeO-NAIP (para-methoxy N-methyl indanylidene-pyrrolinium), which was designed specifically to mimic the photoisomerization of retinal.

MeO-NAIP in methanol achieves a quantum efficiency of about 50% — already impressive, but roughly 17 percentage points below rhodopsin. The simulations reveal precisely why. The answer lies not in the rotary motion itself, but in a previously unrecognized supporting role played by a completely different molecular vibration.

THE PROMOTER VIBRATION: NATURE'S HIDDEN TRICK

The key finding: effective light-energy conversion in rhodopsin requires an auxiliary molecular vibration — called a "promoter" — that does not itself perform the rotary motion, but instead synchronizes with it at specific, critical moments during the excited-state dynamics. This promoter is a wag-type vibrational mode involving the hydrogen atom at the isomerization center. By wagging in synchrony with the rotary motion, it steers the molecule toward the conical intersection funnel that leads to productive photoisomerization — and away from the pathways that waste the absorbed photon energy.

Nature has designed rhodopsin to exploit this vibrational synchronization through two coupled mechanisms. The first ensures that approximately 75% of absorbed photons lead to unidirectional rotations — that is, the chromophore rotates in the correct direction rather than backward or in a nonproductive manner. The second mechanism ensures that this process happens fast enough to avoid directional randomization, which would reduce the overall efficiency. Both mechanisms operate in a vibrationally coherent regime — meaning the atoms move in a coordinated, wave-like fashion rather than randomly.

Nature's secret is synchronization: an auxiliary vibration that doesn't rotate but steers — nudging the molecule toward the productive pathway at precisely the right moment.

WHY MEO-NAIP FALLS SHORT — AND WHAT THAT MEANS

The synthetic rotor MeO-NAIP in methanol is incapable of exploiting either of these mechanisms, the simulations show. The solvent plays a role: in methanol, intermolecular interactions with solvent molecules disrupt the vibrational coherence that rhodopsin achieves within the protective, precisely shaped binding pocket of the protein. Without that coherence, the promoter vibration cannot synchronize effectively with the rotary motion, and the quantum efficiency drops by roughly half.

Strikingly, when the solvent is removed and MeO-NAIP is simulated in the gas phase — where solvent interactions are absent — the quantum efficiency recovers significantly. This result confirms that it is not an intrinsic flaw in MeO-NAIP's molecular design that limits its efficiency, but rather the disruptive effect of the solvent on vibrational coherence. The protein environment of rhodopsin protects its chromophore from exactly this disruption — a function that the synthetic rotor in solution cannot replicate.

WHY IT MATTERS

This paper establishes a concrete, mechanistically grounded design principle for synthetic molecular rotors: if you can engineer a molecule — or its environment — to support a promoter vibration that synchronizes coherently with the rotary motion, you should be able to approach the quantum efficiency of biological rhodopsin. The principle is not unique to MeO-NAIP; it may apply broadly to any light-driven molecular motor that operates through a photoisomerization mechanism.

The practical implications extend to the design of molecular machines, light-driven drug delivery systems, and artificial photosynthesis — any application where getting the most productive chemistry out of every absorbed photon is important. For the Olivucci group, this paper is also a milestone in the ARM (Automatic Rhodopsin Modeling) program: it demonstrates that the quantum-classical trajectory methodology, originally developed to understand biological rhodopsins, is powerful enough to explain — and now guide — the design of synthetic counterparts.

BGSU PhD student Madushanka Manathunga (now at Michigan State) and postdoctoral researcher Alejandro Blanco-González made central contributions to this work, alongside collaborator Xuchun Yang. Their combined mastery of the QM/MM trajectory methodology and photochemical interpretation produced what the Springer Nature research community called "a detailed examination of the quantum mechanical mechanisms underlying energy conversion in molecular rotors" that "brings to light significant findings regarding the quantum efficiency of synthetic molecular rotors in comparison with biological systems."

RESEARCH IN CONTEXT

A Nature Communications Paper, a Design Principle, and 40 Years of CPS Science

This *Nature Communications* paper is one of the high-water marks of the Olivucci group's 2024 output — published in a flagship interdisciplinary journal and immediately picked up by the Springer Nature research community blog as a paper of note. It also exemplifies the CPS's tradition of pursuing questions that sit at the boundary between physics, chemistry, and biology, using computational tools of the highest sophistication to answer them.

The finding that vibrational synchronization — rather than any specific chemical feature of the chromophore — is the key to rhodopsin's quantum efficiency is a result that will inform synthetic chemistry, materials science, and molecular biology alike. It is exactly the kind of discovery that the Center for Photochemical Sciences has been producing for four decades: fundamental, mechanistically rigorous, and with a clear path from basic science to application.

2024 Publication — Olivucci Laboratory

Blanco-González, A., Manathunga, M., Yang, X., & Olivucci, M. (2024). Comparative Quantum-Classical Dynamics of Natural and Synthetic Molecular Rotors Show How Vibrational Synchronization Modulates the Photoisomerization Quantum Efficiency. Nature Communications, 15, 3388. https://doi.org/10.1038/s41467-024-47477-0

FACULTY RESEARCH SPOTLIGHT · 2024

From Radiation Detectors to Quantum Computers: Quantum Shells Prove Their Versatility in a Landmark Year

Mikhail Zamkov, Ph.D.  ·  Professor  ·  Department of Physics and Astronomy & Center for Photochemical Sciences

The year 2024 marked a turning point for the Zamkov Lab's quantum shell research program at BGSU. With four peer-reviewed publications spanning three journals — including two papers in Nature Communications and ACS Nano that established quantum shells as viable platforms for both scintillation and quantum information science — the group demonstrated that the quantum shell architecture is not a single-application technology but a versatile platform with implications across multiple high-impact fields.

The common thread through all four 2024 papers is the suppression of Auger recombination — the non-radiative process that has historically limited quantum dot performance under high excitation conditions. By confining electrons and holes to a thin semiconductor shell rather than a solid dot, the Zamkov Lab's quantum shell design substantially reduces the rate of Auger recombination, enabling the multiexciton emission that drives performance in scintillators, lasers, and quantum light sources alike.

From detecting X-rays to generating entangled photons — the same quantum shell architecture, four different applications, one record-breaking year.

01  A Scintillator That Outperforms Everything

Published in: Nature Communications, 15(1), 4274 · May 20, 2024

Authors: B. Guzelturk, B.T. Diroll, J.P. Cassidy, D. Harankahage, M. Hua, X.-M. Lin, V. Iyer, R.D. Schaller, B.J. Lawrie, M. Zamkov

DOI: 10.1038/s41467-024-48351-9

Collaborating Institutions: Argonne National Laboratory, Oak Ridge National Laboratory, University of Chicago

A scintillator is a material that converts ionizing radiation — X-rays, gamma rays, fast electrons — into visible light that can be detected by a camera or photodetector. Scintillators are the core sensing elements in medical imaging devices (CT scanners, PET scanners, X-ray detectors), in nuclear safeguards instrumentation, and in high-energy physics experiments. The ideal scintillator is efficient (it converts as much radiation energy into light as possible), fast (it responds and recovers quickly for high-speed imaging), and durable (it resists degradation under sustained radiation exposure).

Traditional scintillators — inorganic crystals like LYSO or NaI — face fundamental tradeoffs between efficiency, speed, and cost. Colloidal nanocrystals have long been proposed as scintillators because they are solution-processable, tunable, and can in principle achieve high efficiencies. But Auger recombination has prevented them from delivering on that promise: at the excitation intensities produced by ionizing radiation, multiple excitons form simultaneously, and Auger recombination converts most of the energy to heat before it can produce light.

This Nature Communications paper demonstrates that quantum shells eliminate this bottleneck. Because Auger recombination is strongly suppressed in the shell geometry, quantum shells maintain high radiative efficiency even when multiple excitons are present — exactly the condition created by ionizing radiation. The results: light yields up to 70,000 photons per MeV at room temperature (among the highest ever reported for colloidal nanocrystals); radioluminescence lifetimes as short as 2.5 nanoseconds with sub-100 picosecond rise times; no measurable afterglow (a critical requirement for high-speed imaging); and stability under X-ray doses exceeding 10⁹ Gray.

The paper also demonstrates X-ray imaging with quantum shells achieving a spatial resolution of 28 line pairs per millimeter — a number competitive with commercial scintillator screens. These results establish quantum shells as a genuine scintillator platform, with performance metrics that challenge traditional materials in every relevant category simultaneously.

70,000 photons per MeV. 2.5 nanosecond response. No afterglow. Stable through a billion Gray of radiation. Quantum shells just rewrote the scintillator record book.

02  Continuously Tunable Red-Spectrum Lasers

Published in: ACS Nano, 18(22), 14661–14671 · June 4, 2024

Authors: I. Tanghe, K. Molkens, T. Vandekerckhove, D. Respekta, A. Waters, J. Huang, J. Beavon, D. Harankahage, C.Y. Lin, K. Chen, D. Van Thourhout, M. Zamkov, P. Geiregat

DOI: 10.1021/acsnano.4c02907

Collaborating Institution: Ghent University (Photonics Research Group & PCN Group)

This ACS Nano paper, a collaboration with the Geiregat group at Ghent University in Belgium, addresses one of the most technically demanding challenges in nanocrystal optics: achieving continuously tunable lasing across the red spectrum using colloidal nanocrystals integrated into photonic crystal cavities.

The key finding is that quantum shells support a qualitatively different optical gain regime than conventional quantum dots — a two-dimensional electron-hole plasma. Unlike the discrete excitonic gain that governs conventional nanocrystal lasing, the 2D plasma regime produces a broad, spectrally continuous gain bandwidth that enables lasing to be tuned across a wide range of red wavelengths simply by varying the pump conditions. This is a fundamentally new observation for colloidal nanocrystals and represents a significant step toward practical, spectrally agile nanocrystal laser devices.

When quantum shells were integrated into silicon nitride photonic crystal cavities — a standard integrated photonics platform — the team demonstrated lasing output that was continuously tunable across the red spectrum. The combination of quantum shell gain physics with the mature silicon nitride cavity platform points toward a path for incorporating colloidal nanocrystal lasers into chip-scale photonic devices.

03  Green Light from Red Emitters

Published in: ACS Nano, 18(18), 10946–10953 · April 2024

Authors: K. Zhao, X. Zhou, X. Li, J. Moon, J. Cassidy, D. Harankahage, Z. Hu, S.M. Savoy, Q. Gu, M. Zamkov, A.V. Malko

DOI: 10.1021/acsnano.4c

Collaborating Institutions: University of Texas at Dallas, Nanohmics Inc.

This ACS Nano paper from the Zamkov-Malko collaboration at UT Dallas demonstrates one of the most striking optical phenomena seen in quantum shells to date: broadband, low-threshold lasing in the green spectral region from nanocrystals that nominally emit in the red.

The effect arises from the quantum shell's unusually broad gain bandwidth — a consequence of the 2D electron-hole plasma regime discussed in the Ghent University paper. When quantum shells are placed into optical nanocavities and pumped above threshold, lasing can emerge not only at the primary emission wavelength but also at shorter (bluer) wavelengths — producing green laser output from nominally red-emitting nanocrystals. This broadband, low-threshold behavior distinguishes quantum shells sharply from conventional quantum dots, where gain is confined to a narrow spectral window near the primary emission wavelength.

The practical implication is significant for display and lighting applications: a single type of quantum shell could potentially serve as a gain medium for lasing across multiple color channels, reducing the complexity of nanocrystal-based optical devices.

04  Quantum Shells Enter the Quantum Information Era

Published in: ACS Nano, 18(44), 30863–30870 · November 5, 2024

Authors: A.A. Marder, S.S. Smith, J. Cassidy, D. Harankahage, Z. Hu, S.M. Savoy, G.C. Schatz, M. Zamkov, A.V. Malko

DOI: 10.1021/acsnano.4c11723

Collaborating Institutions: UT Dallas, Nanohmics Inc., Northwestern University

The fourth 2024 paper from the Zamkov Lab may be the most forward-looking of the series. Where scintillation, lasing, and spectral tunability are applications in photonics and imaging, this paper puts quantum shells squarely in the domain of quantum information science — the emerging field of quantum computing, quantum communication, and quantum sensing that promises to transform computation and encryption.

Quantum information processing requires light sources that can produce single photons or pairs of correlated photons on demand, with high purity and reproducibility. Epitaxial quantum dots — made by expensive molecular-beam epitaxy — have been the leading platform, but their production is non-scalable and their emission wavelengths are hard to tune. Colloidal nanocrystals offer scalable synthesis and tunable emission, but have historically been disqualified by their broad emission linewidths and emission instability, which make it impossible to spectrally separate the single-exciton (X) and biexciton (XX) emission needed to generate triggered photon pairs.

This paper shows that quantum shells overcome these limitations. The suppression of Auger recombination in the shell geometry produces long-lived, stable biexciton emission with a large spectral separation from the single-exciton line — approximately 75–80 meV, far larger than in conventional quantum dots. This separation is sufficient to spectrally resolve X and XX emission, enabling the generation and detection of correlated photon pairs through exciton-biexciton bunching. The paper demonstrates, for the first time in colloidal nanocrystals, the heralded generation of correlated photon pairs — a key primitive operation for quantum information applications.

Heralded correlated photon pairs from a colloidal nanocrystal: a first for the field, and a milestone that places scalable quantum shells on the roadmap for quantum information technology.

For a field that has long assumed quantum information applications require expensive, non-scalable epitaxial materials, this result opens a genuinely new direction. If quantum shells can be produced in solution at low cost and integrated into photonic structures, they could become the basis for scalable quantum light sources that do not require exotic fabrication facilities.

A UNIFIED RESEARCH VISION

Four Applications, One Architecture: The Quantum Shell Platform Comes of Age

Four papers in one year, across scintillation, photonic lasing, broadband gain, and quantum information — each enabled by the same suppression of Auger recombination that the Zamkov Lab has spent years engineering into the quantum shell architecture. Taken together, they demonstrate that quantum shells are not a niche material for one specialized application, but a platform technology whose suppressed Auger recombination unlocks performance across an extraordinary breadth of photonic applications.

Graduate students James Cassidy, Dulanjan Harankahage, Amelia Waters, Jiamin Huang, and Jacob Beavon — whose names appear across all four 2024 papers — have been central to building the synthetic and characterization expertise that makes this output possible. Their work, alongside collaborators at Argonne, Oak Ridge, Ghent, UT Dallas, Northwestern, and Nanohmics, reflects the global interest that the quantum shell program has attracted.

For the Center for Photochemical Sciences — which has always included physics alongside chemistry in its research community — the Zamkov Lab's 2024 output demonstrates that the center's photonic science reaches as far as quantum information, one of the defining technological frontiers of the coming decade.

2024 Publications — Zamkov Laboratory

Guzelturk, B., Diroll, B.T., Cassidy, J.P., Harankahage, D., Hua, M., Lin, X.-M., Iyer, V., Schaller, R.D., Lawrie, B.J., & Zamkov, M. (2024). Bright and Durable Scintillation from Colloidal Quantum Shells. Nature Communications, 15, 4274. https://doi.org/10.1038/s41467-024-48351-9

Tanghe, I., Molkens, K., Vandekerckhove, T., Respekta, D., Waters, A., Huang, J., Beavon, J., Harankahage, D., Lin, C.Y., Chen, K., Van Thourhout, D., Zamkov, M., & Geiregat, P. (2024). Two-Dimensional Electron-Hole Plasma in Colloidal Quantum Shells Enables Integrated Lasing Continuously Tunable in the Red Spectrum. ACS Nano, 18(22), 14661–14671. https://doi.org/10.1021/acsnano.4c02907

Zhao, K., Zhou, X., Li, X., Moon, J., Cassidy, J., Harankahage, D., Hu, Z., Savoy, S.M., Gu, Q., Zamkov, M., & Malko, A.V. (2024). Green Light from Red-Emitting Nanocrystals: Broadband, Low-Threshold Lasing from Colloidal Quantum Shells in Optical Nanocavities. ACS Nano, 18(18), 10946–10953. https://doi.org/10.1021/acsnano.4c

Marder, A.A., Smith, S.S., Cassidy, J., Harankahage, D., Hu, Z., Savoy, S.M., Schatz, G.C., Zamkov, M., & Malko, A.V. (2024). Heralded Generation of Correlated Photon Pairs from CdS/CdSe/CdS Quantum Shells. ACS Nano, 18(44), 30863–30870. https://doi.org/10.1021/acsnano.4c11723

FACULTY RESEARCH SPOTLIGHT · 2024

Rewriting the Rulebook: Sivaguru Group Discovers New Photochemical Reactions in 2024

Jayaraman Sivaguru, Ph.D.  ·  Distinguished University Professor  ·  Associate Director, Center for Photochemical Sciences

Organic photochemistry is a mature field with a well-established set of reactions — [2+2] cycloadditions, Paternò-Büchi reactions, Norrish reactions, and others — whose mechanisms have been studied for decades. Yet the Sivaguru Group at BGSU continues to find new territory in that landscape, discovering reaction pathways that do not fit existing mechanistic frameworks and creating new tools for asymmetric synthesis that exploit those discoveries.

In 2024, the Sivaguru Lab published two papers that exemplify this ongoing expansion of photochemical knowledge. One, appearing in the flagship journal Angewandte Chemie International Edition, reports the discovery of a photochemical [2+4] dimerization reaction from the excited state — a reaction type that should not happen based on conventional thinking, but does. The other, published in Photochemistry and Photobiology, reveals a previously unknown photochemical reactivity of β-enaminones that depends on a subtle structural feature: the ring size of the starting material.

When a molecule does something it theoretically shouldn't, that is where the best photochemistry lives — and the Sivaguru Lab keeps finding exactly those places.

01  Breaking the [2+2] Expectation: A New [2+4] Photodimerization

Published in: Angewandte Chemie International Edition, 63(4) · January 2024

Authors: S. Ahuja, S. Baburaj, L.K. Valloli, S.A. Rakhimov, K. Manal, A. Kushwaha, S. Jockusch, M.D.E. Forbes, J. Sivaguru

DOI: 10.1002/anie.202316662

WHAT WAS EXPECTED

Maleimides are known photochemically for one thing above all else: [2+2] photocycloadditions. When maleimides absorb light and reach their excited triplet state, the reactive double bond in the five-membered ring is set up geometrically and electronically to react with another alkene through a [2+2] process, producing a cyclobutane product. This reaction is so reliably observed, and so well understood, that it is essentially taken as a given in the photochemistry of maleimide systems. When you irradiate an aryl-maleimide, you get a [2+2] product.

Except, as this paper reveals, that is not always what happens.

WHAT ACTUALLY HAPPENED

The Sivaguru Lab discovered that certain aryl-maleimides — those with specific substitution patterns on the N-aryl group — undergo a [2+4] photodimerization rather than the expected [2+2]. Instead of the cyclobutane ring formed by [2+2] addition, the reaction produces a bicyclic product characteristic of a [2+4] (Diels-Alder-type) cycloaddition — a reaction that has no precedent in the photochemistry of maleimides.

The [2+4] dimerization occurs from the excited state, meaning it is light-driven, and it takes place with complete chemoselectivity: no [2+2] product is observed at all under the conditions that produce the [2+4] adduct. This selectivity — one reaction or the other, but not both — suggests that the substitution pattern on the maleimide is not merely modifying the rate of an existing reaction but switching the mechanism to a fundamentally different pathway.

The paper provides a detailed mechanistic rationale for this divergent reactivity, based on photophysical studies of the excited states involved, EPR measurements contributed by Dr. Malcolm Forbes, and analysis of the stereochemistry of the [2+4] photodimer. The collaborative contribution from Forbes — whose EPR expertise provided direct insight into the radical character of the excited states — and from Steffen Jockusch at Columbia University, who contributed time-resolved spectroscopy, exemplifies the kind of multi-expert analysis needed to crack a genuinely novel mechanistic problem.

A maleimide that does [2+4] instead of [2+2]: not a modification of a known reaction, but a different reaction altogether — from the same excited state.

WHY IT MATTERS

The discovery of a [2+4] photodimerization from the excited state of aryl-maleimides adds a genuinely new entry to the catalog of photochemical reactions — not a variation on a known theme, but a new reaction class in a system that had been intensively studied for decades. It also opens a new synthetic pathway to the bicyclic products of [2+4] cycloaddition, which are structurally distinct from the cyclobutanes of [2+2] chemistry and have their own potential applications in materials science and medicinal chemistry. Graduate students Sapna Ahuja, Sruthy Baburaj, and Lakshmy Kannadi Valloli led the experimental work that produced this landmark finding.

02  Ring Size Controls the Reaction: β-Enaminone Photochemistry

Published in: Photochemistry and Photobiology, 100(4), 1068–1077 · 2024

Authors: L.K. Valloli, K. Manal, B. Lewis, S. Jockusch, J. Sivaguru

DOI: 10.1111/php.13889

The second 2024 paper from the Sivaguru Lab explores photochemical reactivity in a structurally simple but behavior-rich system: β-enaminones formed in situ from cyclic 1,3-diketones and activated alkenes. These compounds sit at an interesting intersection of organic synthesis and photochemistry — they contain both enamine and carbonyl functional groups in a geometry that makes them photochemically reactive, but their light-induced reactivity had not been systematically characterized.

The key finding is that the photoproduct formed upon irradiation — the chemoselectivity of the reaction — depends on which cyclic 1,3-diketone is used as the starting material. Specifically, β-enaminones derived from 2-acetylcyclopentanone (a five-membered ring diketone) and those derived from 2-acetylcyclohexanone (a six-membered ring diketone) give different photoproducts under otherwise identical conditions. The ring size of the starting material controls which polyheterocyclic skeleton the reaction produces.

The authors rationalize this chemoselectivity using the Dieckmann-Kón rule — a geometric orbital symmetry principle that predicts which photochemical pathway is accessible based on the arrangement of atoms in the excited state. This mechanistic analysis, developed in collaboration with Steffen Jockusch at Columbia, shows that the five-membered and six-membered ring variants adopt different conformations in their excited states, leading to geometrically distinct orbital approaches and therefore to different products.

This paper is also a preview of deeper mechanistic terrain: the chemoselective behavior it documents in β-enaminones would later become the subject of the 2025 Angewandte Chemie paper from the Sivaguru-Tarnovsky-Olivucci collaboration, where femtosecond spectroscopy and quantum chemical calculations revealed the full excited-state dynamics behind this reactivity.

A UNIFIED RESEARCH VISION

Discovering New Photochemistry: The Sivaguru Lab's 2024 Contributions

Two 2024 papers — one in Angewandte Chemie, one in Photochemistry and Photobiology — and a consistent theme: the Sivaguru Lab keeps finding photochemical reactions that don't fit the established playbook, and then explaining why they happen. Whether it is a [2+4] dimerization where [2+2] was expected, or a ring-size-controlled chemoselectivity in β-enaminones, the group's work consistently extends the frontier of what photochemists know organic molecules can do under light.

These discoveries are not accidental. They emerge from a sustained focus on atropisomeric systems and on reactions where conformational control — restricting how a molecule can orient itself in the excited state — determines the outcome. By designing molecules that direct light-driven reactivity through restricted bond rotation and precise three-dimensional geometry, the Sivaguru group creates the conditions in which unusual photochemistry becomes not just possible, but predictable.

Graduate student Lakshmy Kannadi Valloli appears in both 2024 papers, along with colleagues Kavyasree Manal, Brieanna Lewis, Sapna Ahuja, and Sruthy Baburaj. Their work, in collaboration with Forbes and Jockusch, produced two publications that expand what organic photochemistry is known to be capable of.

2024 Publications — Sivaguru Laboratory

Ahuja, S., Baburaj, S., Valloli, L.K., Rakhimov, S.A., Manal, K., Kushwaha, A., Jockusch, S., Forbes, M.D.E., & Sivaguru, J. (2024). Photochemical [2+4]-Dimerization Reaction from the Excited State. Angewandte Chemie International Edition, 63(4), e202316662. https://doi.org/10.1002/anie.202316662

Valloli, L.K., Manal, K., Lewis, B., Jockusch, S., & Sivaguru, J. (2024). Chemoselective Light-Induced Reactivity of β-Enaminones. Photochemistry and Photobiology, 100(4), 1068–1077. https://doi.org/10.1111/php.13889

FACULTY RESEARCH SPOTLIGHT · 2024

Aptamers Against Cancer's Shield: Tan Lab Pioneers New Methods for PD-L1 Targeting in 2024

Xiaohong Tan, Ph.D.  ·  Assistant Professor  ·  Department of Chemistry & Center for Photochemical Sciences

In cancer immunotherapy, few protein targets have attracted more attention than PD-L1 — the programmed death-ligand 1 protein that tumors display on their surface to suppress immune attack. The success of anti-PD-L1 antibody drugs like atezolizumab has validated PD-L1 as a therapeutic target, but also revealed the limitations of antibody-based approaches: high cost, potential immune side effects, and limited tissue penetration. The search for alternative molecules — cheaper, smaller, and more easily engineered — that can block PD-L1 is an active research priority worldwide.

The Tan Lab at BGSU's Center for Photochemical Sciences focuses on DNA aptamers as exactly this kind of alternative. In 2024, the group published two papers that together advance the state of the art in PD-L1 targeting: one introducing a new method for finding peptide inhibitors that work synergistically with existing aptamers, and one reviewing the broader landscape of aptamer- and peptide-based PD-L1 targeting to contextualize the field's progress.

01  APD: Finding Peptides That Work With Aptamers

Published in: Chemical Communications, 60(59), 7570–7573 · June 2024

Authors: S.P. Arya, S.K.S. Thennakoon, C.M.T. Phuoc, A.P. Silwal, R. Jahan, R.M. Postema, H. Timilsina, A.M. Reynolds, X. Tan

DOI: 10.1039/d4cc02132k

THE CHALLENGE: TWO BINDERS, ONE PROTEIN

One of the most promising strategies for blocking PD-L1 is combining two different ligands that each bind to distinct sites on the protein simultaneously — a strategy called bivalent or heterobivalent targeting. If one ligand binds to site A and another to site B, the combined inhibition is greater than either alone, and the thermodynamics of simultaneous dual binding can produce dramatically enhanced overall affinity. The challenge is finding two ligands that actually bind at different sites without competing.

The Tan Lab has been developing DNA aptamers against PD-L1 for several years. The 2024 Chemical Communications paper introduces a new method called Aptamer-assisted Phage Display (APD) — a clever extension of classical phage display that uses an existing aptamer as a "blocker" to force the discovery of peptides that bind elsewhere on the same protein.

HOW APD WORKS

In classical phage display, a library of bacteriophage — each displaying a different short peptide on its surface — is incubated with the target protein, and phage that bind tightly are selected and amplified through multiple rounds. APD adds a critical twist: before exposing the phage library to PD-L1, the aptamer MJ5C — a previously identified anti-PD-L1 aptamer from the Tan Lab — is first allowed to bind and occupy its site on the protein. The phage library is then incubated with this aptamer-occupied PD-L1, meaning any phage that binds must bind somewhere other than where MJ5C sits.

Through this process, the team identified NV Pep: a peptide that binds PD-L1 at a site distinct from MJ5C's binding site, confirmed to bind simultaneously with MJ5C rather than competing with it. The key biological result: combining NV Pep and MJ5C together inhibited the PD-1/PD-L1 interaction significantly more effectively than either ligand alone. The synergistic inhibition demonstrates that bivalent targeting — using two different molecules to block a single protein at two distinct sites — is achievable with a peptide-aptamer combination.

Use the aptamer to block one site, then find a peptide that binds everywhere else: APD turns the aptamer from a binder into a molecular mask — and it works.

WHY IT MATTERS

APD is a generalizable method. Any aptamer that binds a protein of interest can in principle be used as the blocking agent in an APD campaign to identify peptides that bind at complementary sites. This means the method can be applied to any target where bivalent inhibition might be advantageous — which in practice includes many cancer-related proteins, viral entry proteins, and enzyme active sites. The 2024 paper establishes the proof-of-concept on PD-L1, a target with direct clinical relevance, and provides the experimental framework for extending APD to other systems.

02  The Landscape of PD-L1 Aptamer and Peptide Targeting

Published in: Frontiers in Bioscience (Elite Edition), 16(3):28 · September 2024

Authors: H.P. Timilsina, S.P. Arya, X. Tan

DOI: 10.31083/j.fbe1603028

The second 2024 paper from the Tan Lab is a review article — a synthesis of the current state of knowledge on aptamers and peptides as tools for targeting the PD-1/PD-L1 immunosuppressive axis. Published in Frontiers in Bioscience, the review situates the Tan Lab's experimental work in its broader scientific and clinical context.

The review covers the biology of the PD-1/PD-L1 checkpoint, the limitations of antibody-based checkpoint inhibitors, and the case for aptamers and peptides as alternative platforms. It surveys published aptamers and peptides that target PD-L1, evaluating their binding affinities, selectivities, and demonstrated efficacy in blocking the PD-1/PD-L1 interaction. It also discusses the engineering strategies — including aptamer truncation, chemical modification, and the kind of bivalent aptamer-peptide combination that the APD paper demonstrates — that researchers are using to improve on first-generation molecules.

For the research community, this review provides a timely and authoritative roadmap of where the field stands and where it is heading. For the Tan Lab, it contextualizes the APD paper's contribution within the broader effort to develop non-antibody alternatives for cancer immunotherapy — and signals the group's growing role as a thought leader in this space.

RESEARCH IN CONTEXT

The PD-L1 Program: From Aptamers to Synergistic Inhibition

The Tan Lab's two 2024 papers on PD-L1 — one an experimental advance, one a synthetic review — reflect the dual nature of a research program that is both building new methods and positioning itself within the scientific conversation about where cancer immunotherapy is heading.

APD is a significant methodological contribution that will be useful to any laboratory working with aptamers against multi-site protein targets. The review establishes the Tan Lab as a leading voice on the use of nucleic acid and peptide tools for immune checkpoint targeting. Together, they set the stage for the 2025 ACS Biomaterials Science & Engineering paper — in which the AADS methodology, a conceptual cousin of APD, produced the first dual-site DNA fusion aptamers against PD-L1 — demonstrating the rapid pace at which the group is building on its own innovations.

Graduate students Satya Prakash Arya, Siddhartha Kalpa Samadhi Thennakoon, Hari Timilsina, Achut Prasad Silwal, Raunak Jahan, Rick Mason Postema, Chien Minh Tran Phuoc, and Andrew Michael Reynolds contributed to the 2024 Chemical Communications paper — reflecting the full cohort of the Tan Lab working toward a common scientific goal. As the CPS marks its 40th anniversary, this team-driven approach to molecular biology and chemical biology research exemplifies the center's tradition of training scientists who work at the boundaries of disciplines.

2024 Publications — Tan Laboratory

Arya, S.P., Thennakoon, S.K.S., Phuoc, C.M.T., Silwal, A.P., Jahan, R., Postema, R.M., Timilsina, H., Reynolds, A.M., & Tan, X. (2024). Aptamer-Assisted Phage Display: Enhancing Checkpoint Inhibition with a Peptide and an Aptamer Targeting Distinct Sites on a Single PD-L1 Protein. Chemical Communications, 60(59), 7570–7573. https://doi.org/10.1039/d4cc02132k

Timilsina, H.P., Arya, S.P., & Tan, X. (2024). Biotechnological Advances Utilizing Aptamers and Peptides Refining PD-L1 Targeting. Frontiers in Bioscience (Elite Edition), 16(3):28. https://doi.org/10.31083/j.fbe1603028