Rui Liu

Porphyrin and related tetrapyrrole chromophores underpin broad applications in photochemistry, photomedicine, catalysis, and functional materials, yet practical workflows that connect molecular design, geometry optimization, orbital-energy prediction, and absorption spectrum prediction remain fragmented across separate computational tools. Here, we report BeyondPhoton, a modular web- and software-based platform that enables automated porphyrin molecular design and electronic absorption spectral prediction within a single continuous workflow. Four interconnected but independently operable Flask applications communicate through lightweight JSON data exchange, allowing users to proceed from de novo molecular construction or direct SMILES input to geometry optimization, structural visualization, frontier molecular orbital energy prediction, and UV–Vis–NIR spectral simulation without manual file conversion. Predicted HOMO−1, HOMO, LUMO, and LUMO+1 energies are translated into B_y, B_x, Q_y, and Q_x transitions using the Gouterman four-orbital model with empirical correction and Gaussian broadening. Interactive visualization, automated peak annotation, and batch-exportable data formats support rapid screening and downstream analysis. This integrated platform organizes porphyrin spectral prediction into transparent modules, reducing workflow fragmentation and providing a scalable computational infrastructure for tetrapyrrole molecular design in photoscience applications.

Proton-coupled electron transfer (PCET) reactions mediate essential biological energy-conversion processes, yet dynamical experiments that distinguish concerted electron/proton motion from sequential electron-transfer/proton-transfer pathways are unprecedented on ultrafast time scales. Here we report a tightly coupled donor–spacer–acceptor assembly, NDI-Sp-PhOH/BI, that enables direct interrogation of light-triggered and ultrafast PCET dynamics. Photoexcitation of the naphthalene diimide chromophore drives charge separation forming NDI radical anion and benzimidazolium phenoxy radical (PhO•/BIH+) products with a 440 fs time constant, followed by thermal charge recombination on a 5 ps time scale. Transient visible/near-infrared and mid-infrared spectroscopies independently track electron and proton motion and reveal coincident formation and decay of the charge-separated PCET products, excluding detectable phenol radical cation or phenoxide intermediates expected for sequential electron transfer-proton transfer (ET-PT) pathways. Surface-hopping quasiclassical trajectory simulations demonstrate rapid proton relocation coupled to evolution from locally excited to charge-transfer states, congruent with a concerted mechanism. These combined spectroscopic and computational results establish NDI-Sp-PhOH/BI as an archetype for ultrafast, concerted PCET occurring with unit quantum yield; further, because this platform provides distinct electronic and vibrational spectroscopic handles in its ground, electronically excited, and charge-separated states, it provides new opportunities to characterize mechanistic crossover in biomimetic PCET systems.

Understanding the UV-Vis-NIR electronic spectra of tetrapyrrole macrocycles (porphyrins, chlorins, and bacteriochlorins) is crucial to rational designs of novel functional molecules and materials for energy conversion, catalysis, bio-imaging, and medical applications. Despite this, no methods have been defined to enable high throughput screening for a large body of tetrapyrrole molecules ([Formula: see text]) in a short-time period and accurately predict their electronic absorption spectra. Traditional time dependent-density functional theory (TD-DFT) method is cheap for single molecule simulation, but it can be expensive and time-consuming for massive numbers of molecules . Using a combination of computational chemistry, Gouterman four-orbital model, and machine learning methods, we show accurate predictions of the electronic absorption spectra of tetrapyrroles bearing various peripheral substituents across the UV-Vis-NIR spectral regions. Optimized AutoGluon pipelines trained on the full data set achieve high predictive fidelity (R² = 0.985 validation, 0.936 test; mean/median errors < 0.1 eV) and generalized well across the metal-free porphyrin, chlorin, and bacteriochlorin scaffolds represented in this study. Together, this work establishes an efficient (cost and time), scalable, and mechanistically grounded framework for predicting tetrapyrrole electronic absorption spectra, offering broad utilities in rational designs of tetrapyrrole-based functional materials for real-world applications.

Understanding the UV-Vis-NIR electronic spectra of tetrapyrrole macrocycles (porphyrins, chlorins, and bacteriochlorins) is crucial to rational designs of novel functional molecules and materials for energy conversion, catalysis, bio-imaging, and medical applications. Despite this, no methods have been defined to accurately predict the electronic absorption spectra of tetrapyrrole molecules bypassing the expensive and time-consuming TDDFT calculations and enable high throughput screening for thousands of molecules in a short-time period. Using a combination of computational chemistry, Gouterman four-orbital model, and machine learning methods, we show accurate predictions of the electronic absorption spectra of tetrapyrroles bearing various peripheral substituents across the UV-Vis-NIR spectral regions. Optimized AutoGluon pipelines trained on the full data set achieve high predictive fidelity (R² = 0.985 validation, 0.936 test; mean/median errors < 0.1 eV) and robust transferability across different macrocyclic scaffolds. Together, this work establishes an efficient (cost and time), scalable, and mechanistically grounded framework for predicting tetrapyrrole electronic absorption spectra, offering broad utilities in rational designs of tetrapyrrole-based functional materials for real-world applications.

De novo protein design provides a framework to test our understanding of protein function and to build proteins with cofactors and functions not found in nature. Here, we report the design of proteins designed to bind powerful photooxidants and the evaluation of the use of these proteins to generate diffusible small molecule reactive species for applications in proximity labeling. Because excited state dynamics are influenced by the dynamics and hydration of a photo-oxidant’s environment, it was important to not only design a binding site, but also to evaluate its dynamic properties. Thus, we used computational design in conjunction with molecular dynamics (MD) simulations to design a protein, designated NBP ( N DI B inding P rotein) that held a naphthalenediimide (NDI), a powerful photooxidant, in a programable molecular environment. Solution NMR confirmed the structure of the complex. We evaluated two NDI cofactors in this de novo protein, using ultra-fast pump-probe spectroscopy to evaluate light-triggered intra- and intermolecular electron transfer function. Moreover, we demonstrated the utility of this platform to activate multiple molecular probes for protein proximity labeling.

The syntheses of two triads are reported. Each triad is composed of two perylene-monoimides linked to a porphyrin via an ethyne unit, which bridges the perylene 9-position and a porphyrin 5- or 15-position. Each triad also contains a single tether composed of an alkynoic acid or an isophthalate unit. Each triad provides panchromatic absorption (350–700 nm) with fluorescence emission in the near-infrared region (733 or 743 nm; fluorescence quantum yield ~0.2). The syntheses rely on the preparation of trans-AB-porphyrins bearing one site for tether attachment (A), an aryl group (B), and two open meso-positions. The AB-porphyrins were prepared by the condensation of a 1,9-diformyldipyrromethane and a dipyrromethane. The installation of the two perylene-monoimide groups was achieved upon the 5,15-dibromination of the porphyrin and the subsequent copper-free Sonogashira coupling, which was accomplished before or after the attachment of the tether. The syntheses provide relatively straightforward access to a panchromatic absorber for use in bioconjugation or surface-attachment processes.

Understanding how the complex interplay among excitonic interactions, vibronic couplings, and reorganization energy determines coherence-enabled transport mechanisms is a grand challenge with both foundational implications and potential payoffs for energy science. We use a combined experimental and theoretical approach to show how a modest change in structure may be used to modify the exciton delocalization, tune electronic and vibrational coherences, and alter the mechanism of exciton transfer in covalently linked cofacial Zn-porphyrin dimers (meso-beta linked AB_m-β and meso–meso linked AA_m-m). While both AB_m-β and AA_m-m feature zinc porphyrins linked by a 1,2-phenylene bridge, differences in the interporphyrin connectivity set the lateral shift between macrocycles, reducing electronic coupling in AB_m-β and resulting in a localized exciton. Pump–probe experiments show that the exciton dynamics is faster by almost an order of magnitude in the strongly coupled AA_m-m dimer, and two-dimensional electronic spectroscopy (2DES) identifies a vibronic coherence that is absent in AB_m-β. Theoretical studies indicate how the interchromophore interactions in these structures, and their system-bath couplings, influence excitonic delocalization and vibronic coherence-enabled rapid exciton transport dynamics. Real-time path integral calculations reproduce the exciton transfer kinetics observed experimentally and find that the linking-modulated exciton delocalization strongly enhances the contribution of vibronic coherences to the exciton transfer mechanism, and that this coherence accelerates the exciton transfer dynamics. These benchmark molecular design, 2DES, and theoretical studies provide a foundation for directed explorations of nonclassical effects on exciton dynamics in multiporphyrin assemblies.

Solubilization of hydrophobic tetrapyrrole macrocycles and other fluorophores in aqueous solution has been achieved by covalent attachment to the terminus of an amphiphilic polymer, thereby affording a single-fluorophore–single-chain nanoparticle (SCNP). The polymer is a heterotelechelic random polyacrylate/polyacrylamide copolymer bearing hydrophobic and hydrophilic pendant groups. The polymer has a folded unimeric morphology (∼13 nm hydrodynamic diameter) in 1 M NaCl aqueous solution as indicated by dynamic light-scattering spectroscopy. Five hydrophobic organic fluorophores (coumarin, perylene, two chlorins, one phthalocyanine) have been synthesized with a conjugatable tether. Covalent conjugation of the fluorophore–maleimide to the polymer terminus via thiol–maleimide reaction was carried out in DMF. The resulting fluorophore–SCNP in 1 M NaCl aqueous solution exhibited spectral features and fluorescence quantum yield comparable to those of the respective hydrophobic benchmark in toluene. This single-fluorophore–single-polymer strategy bypasses the challenging and often idiosyncratic syntheses of water-soluble tetrapyrrole macrocycles by using the polymer as a general aqueous solubilization package, and in so doing opens up opportunities for the application of hydrophobic fluorophores in the life sciences.

A hydrophobic dipyrrin has been attached to a heterotelechelic amphiphilic random copolymer as part of a single-polymer–single-cargo strategy. The polymer–dipyrrin (“Pod-dipyrrin”) exhibits an extended conformation in the organic solvent N,N-dimethylformamide (DMF) but in aqueous solution forms a unimeric nanoparticle (i.e., a foldamer) as indicated by dynamic light-scattering (DLS) data (hydrodynamic diameter D_h = 140 nm versus 15 nm in the two solvents, respectively). Treatment of the Pod-dipyrrin with Zn(II) in aqueous solution causes formation of a bis(Pod-dipyrrinato)Zn(II) complex as evidenced by a (1) slight change in absorption spectrum, (2) ∼50-fold increase in fluorescence quantum yield (Φ_f from 0.0035 to 0.17), and (3) profound increase in D_h (from 15 nm to 260 nm). The D_h value for the bis(Pod-dipyrrinato)Zn(II) complex is only slightly smaller in water (260 nm) than in DMF (310 nm), where a more extended conformation is expected. The increase in fluorescence of the bis(Pod-dipyrrinato)Zn(II) complex is readily observed by visual inspection (i.e., naked-eye readout). The conversion of a compact folded unimer (15 nm) to a more extended dimer (260 nm) triggered by metal ion addition denotes a conformationally malleable, environmentally sensitive molecular architecture. The self-assembly process can be reversed upon treatment with a metal-ion sequestering agent such as EDTA. The facile synthesis of a fluorogenic architecture that undergoes profound spontaneous change in molecular morphology upon binding an exogenous agent in water under physiological conditions may open a number of opportunities for sensory-mechanical studies in the life sciences.