Via conversion to Katritzky pyridinium salts, alkyl amines can now be used as alkyl radical precursors for a range of deaminative functionalization reactions. The key step of all of these methods is single-electron reduction of the pyridinium ring, which triggers C−N bond cleavage. However, little has been done to understand how the precise nature of the pyridinium influences these events. Using a combination of synthesis, computation, and electrochemistry, this study delineates the steric and electronic effects that substituents have on the canonical steps and the overall process. Depending on the approach taken, consideration of both the reduction and the subsequent radical dissociation may be necessary. Whereas the electronic effects on these steps work in opposition to each other, the steric effects are synergistic, with larger substituents favoring both steps. This understanding provides a framework for future design of pyridinium salts to match the mode of catalysis or activation.

Two brominated 10,10-dimethylisocorrole (10-DMIC) derivatives containing Pd­(II) centers have been prepared and characterized. These compounds were prepared via bromination of 10,10-dimethylbiladiene-based oligotetrapyrroles. Bromination of free base 10,10-dimethylbiladiene (DMBil1) followed by metalation with Pd­(OAc)2, as well as bromination of the corresponding Pd­(II) dimethylbiladiene complex (Pd­[DMBil1]) provide routes to Pd­(II) hexabromo-10,10-dimethyl-5,15-bis­(pentafluorophenyl)-isocorrole (Pd­[10-DMIC-Br6 ]) and Pd­(II) octabromo-10,10-dimethyl-5,15-bis­(pentafluorophenyl)-isocorrole (Pd­[10-DMIC-Br8 ]). The solid-state structures of the two brominated isocorrole complexes are presented, as is that for a new decabrominated dimethylbiladiene derivative (DMBil-Br10 ). The electronic and spectroscopic properties of the brominated biladiene and isocorrole derivatives were probed using a combination of voltammetric methods and steady-state UV–vis absorption and emission experiments. Data obtained from these experiments allow the properties of the brominated biladiene and isocorrole derivatives to be compared to previously studied biladiene derivatives (i.e., DMBil1 and Pd­[DMBil1]). CV and DPV experiments demonstrate that Pd­[10-DMIC-Br6] and Pd­[10-DMIC-Br8] support well-behaved multielectron redox chemistry, similar to that which has been observed for other nonaromatic tetrapyrroles containing sp3-hybridized meso-carbons. Spectroscopic experiments reveal that bromination of the dimethylbiladiene core shifts this system’s UV–vis absorption profile to lower energy and that the dimethylisocorrole complexes support panchromatic absorption profiles that extend across the UV–vis and into the near-IR region. Photosensitization experiments demonstrate that unlike previously studied Pd­(II) biladiene constructs, DMBil-Br10 , Pd­[10-DMIC-Br6], and Pd­[10-DMIC-Br8] support limited triplet excited state chemistry with O2, indicating that the novel nonaromatic tetrapyrrole derivatives described in this work may be best suited for applications other than singlet oxygen sensitization.

A set of Pd(II) biladiene complexes bearing different combinations of methyl-and phenyl-substituents on the sp 3 -hybridized meso-carbon (the 10-position of the biladiene framework) was prepared and studied. In addition to a previously described Pd(II) biladiene complex bearing geminal dimethyl substituents a the 10-position (Pd[DMBil]), homologous Pd(II) biladienes bearing geminal methyl and phenyl substituents (Pd[MPBil1]) and geminal diphenyl groups-(Pd[DPBil1]) were prepared and structurally characterized. Detailed electrochemical as well as steady-state and time-resolved spectroscopic experiments were undertaken to evaluate the influence of the substituents on the biladiene's tetrahedral meso-carbon. Although all three biladiene homologues are isostructural, Pd[MPBil1] and Pd[DPBil1] display more intense absorption profiles that shift slightly toward lower energies as geminal methyl groups are replaced by phenyl rings. All three biladiene homologues support a triplet photochemistry, and replacement of the geminal dimethyl substituents of Pd[DMBil1] (Φ Δ = 54%) with phenyl groups improves the ability of Pd[MPBil1] (Φ Δ = 76%) and Pd[DPBil1] (Φ Δ = 66%) to sensitize 1 O 2 . Analysis of the excited-state dynamics of the Pd(II) biladienes by transient absorption spectroscopy shows that each complex supports a long-lived triplet excited-state (i.e., τ > 15 μs for each homologue) but that the ISC quantum yields (Φ T ) varied as a function of biladiene substitution. The observed trend in ISC efficiency matches that for singlet oxygen sensitization quantum yields (Φ Δ ) across the biladiene series considered in this work. The results of this study provide new insights to guide future development of biladiene based agents for PDT and other photochemical applications.

Photothermal therapy (PTT) is a promising treatment option for diseases, including cancer, arthritis, and periodontitis. Typical photothermal agents (PTAs) absorb light in the near-infrared (NIR)-I region of 650–900 nm with a predominant focus around 800 nm, as these wavelengths are minimally absorbed by water and blood in the tissue. Recently, interest has grown in developing nanomaterials that offer more efficient photothermal conversion and that can be excited by light close to or within the NIR-II window of 1000–1700 nm, which offers less absorption by melanin. Herein, we report on the development of 5,5-diphenyl isocorrole (5-DPIC) complexes containing either Zn­(II) or Pd­(II) (Zn­[5-DPIC] and Pd­[5-DPIC], respectively) that absorb strongly across the 850–1000 nm window. We also show that poly­(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with these designer isocorroles exhibit low toxicity toward triple-negative breast cancer (TNBC) cells in the dark but enable efficient heat production and photothermal cell ablation upon excitation with 980 nm light. These materials represent an exciting new platform for 980 nm activated PTT and demonstrate the potential for designer isocorroles to serve as effective PTAs.

The selective 4e–/4H+ reduction of dioxygen to water is an important reaction that takes place at the cathode of fuel cells. Monomeric aromatic tetrapyrroles (such as porphyrins, phthalocyanines, and corroles) coordinated to Co­(II) or Co­(III) have been considered as oxygen reduction catalysts due to their low cost and relative ease of synthesis. However, these systems have been repeatedly shown to be selective for O2 reduction by the less desired 2e–/2H+ pathway to yield hydrogen peroxide. Herein, we report the initial synthesis and study of a Co­(II) tetrapyrrole complex based on a nonaromatic isocorrole scaffold that is competent for 4e–/4H+ oxygen reduction reaction (ORR). This Co­(II) 10,10-dimethyl isocorrole (Co­[10-DMIC]) is obtained in just four simple steps and has excellent yield from a known dipyrromethane synthon. Evaluation of the steady state spectroscopic and redox properties of Co­[10-DMIC] against those of Co porphyrin (cobalt 5,10,15,20-tetrakis­(pentafluorophenyl)­porphyrin, [Co­(TPFPP)]) and corrole (cobalt 5,10,15-tris­(pentafluorophenyl)­corrole triphenylphosphine, Co­[TPFPC]­(PPh 3 )) homologues demonstrated that the spectroscopic and electrochemical properties of the isocorrole are distinct from those displayed by more traditional aromatic tetrapyrroles. Further, the investigation of the ORR activity of Co­[10-DMIC] using a combination of electrochemical and chemical reduction studies revealed that this simple, unadorned monomeric Co­(II) tetrapyrrole is ∼85% selective for the 4e–/4H+ reduction of O2 to H2O over the more kinetically facile 2e–/2H+ process that delivers H2O2. In contrast, the same ORR evaluations conducted for the Co porphyrin and corrole homologues demonstrated that these traditional aromatic systems catalyze the 2e–/2H+ conversion of O2 to H2O2 with near complete selectivity. Despite being a simple, easily prepared, monomeric tetrapyrrole platform, Co­[10-DMIC] supports an ORR catalysis that has historically only been achieved using elaborate porphyrinoid-based architectures that incorporate pendant proton-transfer groups or ditopic molecular clefts or that impose cofacially oriented O2 binding sites. Accordingly, Co­[10-DMIC] represents the first simple, unadorned, monomeric metalloisocorrole complex that can be easily prepared and shows a privileged performance for the 4e–/4H+ peractivation of O2 to water as compared to other simple cobalt containing tetrapyrroles.