Electron-Withdrawing meso-Substituents Turn On Magneto-Optical Activity in Porphyrins.

A series of square planar metalloporphyrins (M(TPP), TPP is 5,10,15,20-tetraphenylporphyrin and M(TPFPP), TPFPP is 5,10,15,20-tetrapentafluorophenylporphyrin; M is Zn2+, Ni2+, Pd2+, or Pt2+) with distinct meso-substituents were prepared, and their magneto-optical activity (MOA) was characterized by magnetic circular dichroism (MCD) and magneto-optical rotary dispersion spectroscopy (MORD; also known as Faraday rotation spectroscopy). MOA is crucial in the development of next-generation magneto-optical devices and quantum computing. The data show that the presence of meso-pentafluorophenyl substituents results in significant increase in MOA in comparison to the homologous phenyl group. Differences in the MOA of these metalloporphyrins are rationalized using the Gouterman four-orbital model and pave the way for rational design of improved and tailorable magneto-optical materials.

Mapping the influence of ligand electronics on the spectroscopic and 1O2 sensitization characteristics of Pd(II) biladiene complexes bearing phenyl-alkynyl groups at the 2- and 18-positions.

Photodynamic therapy (PDT) is a promising treatment for certain cancers that proceeds via sensitization of ground state 3O2 to generate reactive 1O2. Classic macrocyclic tetrapyrrole ligand scaffolds, such as porphyrins and phthalocyanines, have been studied in detail for their 1O2 photosensitization capabilities. Despite their compelling photophysics, these systems have been limited in PDT applications because of adverse biological side effects. Conversely, the development of non-traditional oligotetrapyrrole ligands metalated with palladium (Pd[DMBil1]) have established new candidates for PDT that display excellent biocompatibility. Herein, the synthesis, electrochemical, and photophysical characterization of a new family of 2,18-bis(phenylalkynyl)-substituted PdII 10,10-dimethyl-5,15-bis(pentafluorophenyl)-biladiene (Pd[DMBil2-R]) complexes is presented. These second generation biladienes feature extended conjugation relative to previously characterized PdII biladiene scaffolds (Pd[DMBil1]). We show that these new derivatives can be prepared in good yield and, that the electronic nature of the phenylalkynyl appendages dramatically influence the PdII biladiene photophysics. Extending the conjugation of the Pd[DMBil1] core through installation of phenylacetylene resulted in a ∼75 nm red-shift of the biladiene absorption spectrum into the phototherapeutic window (600-900 nm), while maintaining the PdII biladiene's steady-state spectroscopic 1O2 sensitization characteristics. Varying the electronics of the phenylalkyne groups via installation of electron donating or withdrawing groups dramatically influences the steady-state spectroscopic and photophysical properties of the resulting Pd[DMBil2-R] family of complexes. The most electron rich variants (Pd[DMBil2-N(CH3)2]) can absorb light as far red as ∼700 nm but suffer from significantly reduced ability to sensitize formation of 1O2. By contrast, Pd[DMBil2-R] derivatives bearing electron withdrawing functionalities (Pd[DMBil2-CN] and Pd[DMBil2-CF3]) display 1O2 quantum yields above 90%. The collection of results we report suggest that excited state charge transfer from more electron-rich phenyl-alkyne appendages to the electron deficient biladiene core circumvents triplet sensitization. The spectral and redox properties, as well as the triplet sensitization efficiency of each Pd[DMBil2-R] derivative is considered in relation to the Hammett value (σp) for each biladiene's R-group. More broadly, the results reported in this study clearly demonstrate that biladiene redox properties, spectral properties, and photophysics can be perturbed greatly by relatively minor alterations to biladiene structure.

Photoredox-Nickel Dual-Catalyzed C-Alkylation of Secondary Nitroalkanes: Access to Sterically Hindered α-Tertiary Amines.

The preparation of tertiary nitroalkanes via the nickel-catalyzed alkylation of secondary nitroalkanes using aliphatic iodides is reported. Previously, catalytic access to this important class of nitroalkanes via alkylation has not been possible due to the inability of catalysts to overcome the steric demands of the products. However, we have now found that the use of a nickel catalyst in combination with a photoredox catalyst and light leads to much more active alkylation catalysts. These can now access tertiary nitroalkanes. The conditions are scalable as well as air and moisture tolerant. Importantly, reduction of the tertiary nitroalkane products allows rapid access to α-tertiary amines.

Elucidation of complex triplet excited state dynamics in Pd(II) biladiene tetrapyrroles.

Pd(II) biladienes have been developed over the last five years as non-aromatic oligotetrapyrrole complexes that support a rich triplet photochemistry. In this work, we have undertaken the first detailed photophysical interrogation of three homologous Pd(II) biladienes bearing different combinations of methyl- and phenyl-substituents on the frameworks' sp3-hybridized meso-carbon (i.e., the 10-position of the biladiene framework). These experiments have revealed unexpected excited-state dynamics that are dependent on the wavelength of light used to excite the biladiene. More specifically, transient absorption spectroscopy revealed that higher-energy excitation (λexc ∼ 350-500 nm) led to an additional lifetime (i.e., an extra photophysical process) compared to experiments carried out following excitation into the lowest-energy excited states (λexc = 550 nm). Each Pd(II) biladiene complex displayed an intersystem crossing lifetime on the order of tens of ps and a triplet lifetime of ∼20 µs, regardless of the excitation wavelength. However, when higher-energy light is used to excite the complexes, a new lifetime on the order of hundreds of ps is observed. The origin of the 'extra' lifetime observed upon higher energy excitation was revealed using density functional theory (DFT) and time-dependent DFT (TDDFT). These efforts demonstrated that excitation into higher-energy metal-mixed-charge-transfer excited states with high spin-orbit coupling to higher energy metal-mixed-charge-transfer triplet states leads to the additional excitation deactivation pathway. The results of this work demonstrate that Pd(II) biladienes support a unique triplet photochemistry that may be exploited for development of new photochemical schemes and applications.

Isocorrole-Loaded Polymer Nanoparticles for Photothermal Therapy under 980 nm Light Excitation.

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.

A randomized controlled trial of moral reconation therapy to reduce risk for criminal recidivism among justice-involved adults in mental health residential treatment.

OBJECTIVE: Moral reconation therapy (MRT) is a cognitive-behavioral intervention to reduce risk for criminal recidivism. Despite being implemented widely in correctional settings, there are no randomized controlled trials of MRT, and its effectiveness for reducing recidivism among justice-involved adults in noncorrectional settings is unknown. METHOD: In a pragmatic trial, 341 justice-involved patients (95.3% male; 57.8% White/non-Hispanic) admitted to one of three mental health residential treatment programs were randomly assigned to usual care (UC) or UC plus two MRT groups per week for 12 weeks. Follow-ups were conducted at 6- and 12-month postbaseline (71.3% and 74.8% retention, respectively). Primary outcomes were criminal thinking and criminal associates. Secondary outcomes were legal problem severity, days incarcerated in the past 30, rearrested/charged (per official records), substance use, and employment and family/social problems. The study design, analysis, and outcomes were preregistered (ClinicalTrials.gov; ID: NCT02524171). RESULTS: Patients in both conditions improved over time on most outcomes. In intent-to-treat analyses, the rate of change in outcomes over time did not differ by condition, nor did the prevalence of being rearrested and charged within 1 year of baseline (UC = 20.2%, MRT = 24.9%; OR = 1.14; 95% CI [0.67, 1.94], p = .63). MRT engagement was low; 37% of those randomized to MRT received a minimum dose-that is, completed at least Step 3. In per-protocol analyses, this subgroup, relative to UC, improved more on criminal associates, days incarcerated, legal problem severity, and alcohol use severity. CONCLUSIONS: In this study, MRT was not more effective than UC at reducing recidivism risk for patients in mental health residential treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

An Easily Prepared Monomeric Cobalt(II) Tetrapyrrole Complex That Efficiently Promotes the 4e-/4H+ Peractivation of O2 to Water.

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](PPh3)) 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.

Electrochemically Mediated Oxidation of Sensitive Propargylic Benzylic Alcohols.

The electrochemical oxidation of sensitive propargylic benzylic alcohols having varying substituents is reported. We describe the preparation and characterization of N-hydroxytetrafluorophthalimide (TFNHPI) and pseudo-high-throughput development of a green electrochemical oxidation protocol for sensitive propargylic benzylic alcohols that employs TFNHPI as a stable electrochemical mediator. The electrochemical oxidation of propargylic benzylic alcohols was leveraged to develop short synthetic pathways for preparing gram quantities of resveratrol natural products such as pauciflorols.

Expanding the Scope of Forensic and Other Services for Justice-Involved Veterans.

Military veterans are a unique population within the criminal justice system. Numerous criminal justice reforms for this population exist, but there is a dearth of research summarizing and critiquing past and ongoing efforts directed at veterans. This article examines the partnerships developed by the Department of Veterans Affairs with criminal justice agencies to address the needs of justice-involved veterans. Despite these efforts, there is more to be done to support veterans. We provide recommendations for agencies, including enhanced identification of veterans in criminal justice settings, delivery of services to a wider range of veterans, enhancement of partnered relationships with law enforcement, recalibration of the role of Veterans Treatment Courts in the continuum of justice system offerings, expansion of trauma-informed care throughout the criminal justice and partnered health care systems, and sustainment of reform efforts and innovations through advisory bodies. Rigorous research to evaluate reform efforts are needed across all areas. The Veterans Affairs' continuing role as partner to criminal justice agencies and in reform efforts is critical, and improving linkage to and use of health care will result in enhanced health and other outcomes for veterans involved in the criminal justice system.

Implementation Potential of Moral Reconation Therapy for Criminal Recidivism in Mental Health Residential Programs.

OBJECTIVE: Criminal recidivism is common among patients in mental health residential treatment programs. Moral reconation therapy (MRT) has empirical support for reducing criminal recidivism by modifying antisocial cognitions and behaviors; however, its implementation potential in noncorrectional settings has been rarely studied. This potential was examined in a three-site effectiveness-implementation trial of MRT for justice-involved veterans receiving residential mental health treatment in the U.S. Veterans Health Administration. METHODS: Semistructured interviews were conducted with 36 veterans who received MRT and 13 residential program staff who were involved in its implementation during the trial. Interviews were guided by the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework and a focus on patient engagement and context. Content analysis was used to identify facilitators of and barriers to MRT implementation in residential mental health treatment. RESULTS: Participants viewed MRT as unique and complementary to usual residential care, with benefits beyond recidivism reduction. However, time intensity of the MRT curriculum, challenges in adapting its content and format, and long-term costs of maintaining MRT were viewed as barriers to implementation. To facilitate implementation, participants suggested streamlining the MRT curriculum, adding motivational components, and establishing partnerships in- and outside the health care system. CONCLUSIONS: The findings suggest strategies and modifications to MRT, which, if shown to be effective, may facilitate its wider implementation in mental health residential treatment programs.

A national train-the-trainer program to enhance police response to veterans with mental health issues: Primary officer and trainer outcomes and material dissemination.

Law enforcement officers (LEOs) may play the most important role in directing people in mental health crises into treatment versus incarceration. While most military veterans will never experience a crisis interaction with LEOs, they represent an important at-risk target group for whom to enhance LEO response. The evidence supporting LEO crisis training models includes important limitations that stem from jurisdiction-limited studies, and emphasize LEOs who volunteer for mental health training. The current study reports the primary outcomes of a national (U.S.) large-scale mandated train-the-trainer program to enhance VA LEO response to military veterans with mental health issues. Multidisciplinary teams comprised of VA LEOs, Veterans Justice Outreach Specialists, and mental health professionals (n = 245) were trained in two nested waves. Both trainers and endpoint LEOs (n = 1,284) improved from pretest to posttest on knowledge and skills in identifying psychological services and related treatment referral resources and cross-discipline collaboration, the latter of which showed some retention at 3-month follow-up. The findings support the potential for LEOs mandated to training to improve in important prerequisites to diverting people with mental health issues into care, and away from the criminal justice system. Such results may require professional trainers of LEOs who have themselves received relevant specific training. Potential cautions of such an approach, including inter-team differences and potential for publication bias in extant literature, are also elucidated by the current methodology. The links to all of the collaboratively-developed curriculum materials from the current study are provided for use by qualified professionals. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Dissection of Alkylpyridinium Structures to Understand Deamination Reactions.

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 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.

Synthesis, Electrochemistry, and Photophysics of Pd(II) Biladiene Complexes Bearing Varied Substituents at the sp3-Hybridized 10-Position.

A set of Pd(II) biladiene complexes bearing different combinations of methyl- and phenyl-substituents on the sp3-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] (ΦΔ = 54%) with phenyl groups improves the ability of Pd[MPBil1] (ΦΔ = 76%) and Pd[DPBil1] (ΦΔ = 66%) to sensitize 1O2. 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 (ΦT) varied as a function of biladiene substitution. The observed trend in ISC efficiency matches that for singlet oxygen sensitization quantum yields (ΦΔ) 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.

Facile and Rapid Room-Temperature Electrosynthesis and Controlled Surface Growth of Fe-MIL-101 and Fe-MIL-101-NH2.

The electrochemical synthesis of metal-organic frameworks (MOFs) has been widely explored but has involved indirect routes, including anodic dissolution of solid metal electrodes or the use of interfacial redox chemistry to generate base equivalents and drive MOF assembly. These methods are limited in scope, as the former relies on the use of an anode consisting of the metal ion to be incorporated into the MOF, and the latter relies on the compatibility of the metal/ligand solution with the probase that is subsequently oxidized or reduced. We report the facile, direct electrochemical syntheses of four iron-based MOFs via controlled potential oxidation of dissolved metal cations. Oxidation of Fe(II) at +0.75 V (vs Ag/Ag+) in a solution containing 2,6-lutidine and terephthalic acid affords highly crystalline Fe-MIL-101. Controlled potential electrolysis with carboxy-functionalized ITO affords Fe-MIL-101 grown directly on the surface of modified electrodes. The methods we report herein represent the first general routes that employ interfacial electrochemistry to alter the oxidation state of metal ions dissolved in solution to directly trigger MOF formation. The reported method is functional group tolerant and will be broadly applicable to the bulk synthesis or surface growth of a range of MOFs based on metal ions with accessible oxidation states.

Synthesis, Spectroscopic, and 1O2 Sensitization Characteristics of Extended Pd(II) 10,10-Dimethylbiladiene Complexes Bearing Alkynyl-Aryl Appendages.

Photodynamic therapy (PDT), which involves the photoinduced sensitization of singlet oxygen, is an attractive treatment for certain types of cancer. The development of new photochemotherapeutic agents remains an important area of research. Macrocyclic tetrapyrrole compounds including porphyrins, phthalocyanines, chlorins, and bacteriochlorins have been pursued as sensitizers of singlet oxygen for PDT applications but historically are difficult to prepare/purify and can also suffer from high nonspecific dark toxicity, poor solubility in biological media, and/or slow clearance from biological tissues. In response to these shortcomings, we have developed a series of novel linear tetrapyrrole architectures complexed to late transition metals as potential PDT agents. We find that these dimethylbiladiene (DMBil1) tetrapyrrole complexes can efficiently photosensitize generation of 1O2 oxygen upon irradiation with visible light. To extend the absorption profile of the DMBil1 platform, alkynyl-aryl groups have been conjugated to the periphery of the tetrapyrrole using Sonogashira methods. Derivatives of this type containing ancillary phenyl (DMBil-PE), naphthyl (DMBil-NE), and anthracenyl (DMBil-AE) groups have been prepared and characterized. In addition to structurally characterizing Pd[DMBil-NE] and Pd[DMBil-AE], we find that extension of the tetrapyrrole conjugation successfully red-shifts the absorption of the DMBil-Ar family of biladienes further into the phototherapeutic window (i.e., 600-900 nm). Photochemical sensitization studies demonstrate that our series of new palladium biladiene complexes (Pd[DMBil-Ar]) can sensitize the formation of 1O2 with quantum yields in the range ΦΔ = 0.59-0.73 upon irradiation with light of λ ≥ 650 nm. The improved absorption properties of the Pd[DMBil-Ar] complexes in the phototherapeutic window, together with their high 1O2 quantum yields, highlight the promise of these compounds as potential agents for PDT.

Reversible Proton-Coupled Reduction of an Iron Nitrosyl Porphyrin within [DBU-H]+-Based Protic Ionic Liquid Nanodomains.

The reduction of [Fe(OEP)(NO)] has been studied in the presence of aprotic room-temperature ionic liquids (RTIL) and protic (PIL) ionic liquids dissolved within a molecular solvent (MS). The cyclic voltammetric results showed the formation of RTIL nanodomains at low concentrations of the RTIL/PIL solutions. The pKa values of the two PILs studied (i.e., trialkylammonium and [DBU-H]+-based ionic liquids) differed by four units in THF. While voltammetry in solutions containing all three RTILs showed similar potential shifts of the first reduction of [Fe(OEP)(NO)] to [Fe(OEP)(NO)]- at low concentrations, significant differences were observed at higher concentrations for the ammonium PIL. The trialkylammonium cation had previously been shown to protonate the {FeNO}8 species at room temperature. Visible and infrared spectroelectrochemistry revealed that the [DBU-H]+-based PIL formed hydrogen bonds with [Fe(OEP)(NO)]- rather than formally protonating it. Despite these differences, both PILs were able to efficiently reduce the nitrosyl species to the hydroxylamine complex, which could be further reduced to ammonia. On the voltammetric time scale and when the switching potential was positive of the Fe(II)/Fe(I) potential, the hydroxylamine complex was re-oxidized back to the NO complex via direct oxidation of the coordinated hydroxylamine at low scan rates or initial oxidation of the ferrous porphyrin at high scan rates. The results of this work show that, while [DBU-H]+ does not protonate electrochemically generated [Fe(OEP)(NO)]-, it still plays an important role in efficiently reducing the nitroxyl ligand via a series of proton-coupled electron transfer steps to generate hydroxylamine and eventually ammonia. The overall reaction rates were independent of the PIL concentration, consistent with the nanodomain formation being important to the reduction process.

Recidivism Treatment for Justice-Involved Veterans: Evaluating Adoption and Sustainment of Moral Reconation Therapy in the US Veterans Health Administration.

Moral Reconation Therapy (MRT), an evidence-based intervention to reduce risk for criminal recidivism among justice-involved adults, was developed and primarily tested in correctional settings. Therefore, a better understanding of the implementation potential of MRT within non-correctional settings is needed. To address this gap in the literature, we evaluated the adoption and sustainment of MRT in the US Veterans Health Administration (VHA) following a national training initiative in fiscal years 2016 and 2017. In February 2019, surveys with 66 of the 78 VHA facilities that participated in the training were used to estimate the prevalence of MRT adoption and sustainment, and qualitative interviews with key informants from 20 facilities were used to identify factors associated with sustainment of MRT groups. Of the 66 facilities surveyed, the majority reported adopting (n = 52; 79%) and sustaining their MRT group until the time of the survey (n = 38; 58%). MRT sustainment was facilitated by strong intra-facility (e.g., between veterans justice and behavioral health services) and inter-agency collaborations (e.g., between VHA and criminal justice system stakeholders), which provided a reliable referral source to MRT groups, external incentives for patient engagement, and sufficient staffing to maintain groups. Additional facilitators of MRT sustainment were adaptations to the content and delivery of MRT for patients and screening of referrals to the groups. The findings provide guidance to clinics and healthcare systems that are seeking to implement MRT with justice-involved patient populations, and inform development of implementation strategies to be formally tested in future trials.

Synthesis, Redox, and Spectroscopic Properties of Pd(II) 10,10-Dimethylisocorrole Complexes Prepared via Bromination of Dimethylbiladiene Oligotetrapyrroles.

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.

Gold Nanoshell-Linear Tetrapyrrole Conjugates for Near Infrared-Activated Dual Photodynamic and Photothermal Therapies.

Photodynamic therapy (PDT) is a treatment in which photoactive compounds delivered to cancerous tissues are excited with light and then transfer the absorbed energy to adjacent tissue oxygen molecules to generate toxic singlet oxygen (1O2). As 1O2 is produced only where light and photosensitizers (PSs) are combined, PDT holds promise as a minimally invasive, highly selective treatment for certain cancers. The practical application of PDT requires easily synthesized, water-soluble PSs that have low dark toxicities, high 1O2 quantum yields, and efficient absorption of 650-850 nm near-infrared (NIR) light, which deeply penetrates tissue. We recently developed a linear tetrapyrrole metal complex, Pd[DMBil1]-PEG750, that meets most of these criteria. This complex is remarkably effective as a PS for PDT against triple-negative breast cancer (TNBC) cells but, critically, it does not absorb NIR light, which is necessary to treat deeper tumors. To enable NIR activation, we synthesized a new derivative, Pd[DMBil1]-PEG5000-SH, which bears a thiol functionality that facilitates conjugation to NIR-absorbing gold nanoshells (NSs). Upon excitation with pulsed 800 nm light, NSs emit two-photon-induced photoluminescence spanning 500-700 nm, which can sensitize the attached PSs to initiate PDT. Additionally, NSs produce heat upon 800 nm irradiation, endowing the NS-PS conjugates with an auxiliary photothermal therapeutic (PTT) capability. Here, we demonstrate that NS-PS conjugates are potent mediators of NIR-activated tandem PDT/PTT against TNBC cells in vitro. We show that Pd[DMBil1]-PEG5000-SH retains the photophysical properties of the parent Pd[DMBil1] complex, and that NS-PS generate 1O2 under pulsed 800 nm irradiation, confirming activation of the PSs by photoluminescence emitted from NSs. TNBC cells readily internalize NS PS conjugates, which generate reactive oxygen species in the cells upon pulsed NIR irradiation to damage DNA and induce apoptosis. Together, these findings demonstrate that exploiting photoluminescent NSs as carriers of efficient Pd[DMBil1] PSs is an effective strategy to enable NIR light-activated tandem PDT/PTT.

Role of Electrostatics in Influencing the Pathway by Which the Excited State of [Ru(bpy)3]2+ Is Deactivated by Ferrocene Derivatives.

Excited states of tris(2,2'-bipyridine)ruthenium(II), [Ru(bpy)3]2+, can be deactivated by a wide range of ferrocene derivatives. The pathway by which deactivation takes place, either energy transfer (EnT) or electron transfer (ET), depends on several factors inherent to each specific donor-acceptor (D···A) system. In this work, we provide mechanistic insight into bimolecular quenching between [Ru(bpy)3]2+* and several ferrocene (Fc) derivatives in a variety of solvents. By introducing various functional groups onto the cyclopentadienyl ring of ferrocene, the chemical properties of the organometallic complexes were altered by tuning the oxidation potentials and charge of the iron complexes, and the manner in which the [Ru(bpy)3]2+ excited state is quenched by each ferrocene complex in solvents of various dielectric constants, including anhydrous acetonitrile (ACN), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and water (pH 10), was assessed. Through the use of transient absorption (TA) spectroscopy, the mechanism of [Ru(bpy)3]2+* quenching by each of five ferrocene derivatives (i.e., either EnT or ET) in the aforementioned solvents was evaluated. On the basis of these studies, electrostatic factors relating to the charge on the ferrocene moiety were found to influence the quenching pathway(s) for the [Ru(bpy)3]2+···Fc systems under interrogation. When the ferrocene moiety is positively charged, the [Ru(bpy)3]2+ excited state is quenched by EnT to Fc, while when the ferrocene moiety is neutral or negatively charged, the [Ru(bpy)3]2+ excited state is quenched via reductive ET.