Today a significant number of Gram-negative bacteria have evolved to inactivate traditional antibiotics like penicillin and continue to develop resistance against next-generation antimicrobial drugs at a shocking rate. Taking inspiration from actinobacteria (order Actinomycetales) that make reactive enediynes with a (Z)-1,5-diyn-3-ene core to arm themselves, we report the photoactivation of the enediyne precursor octa-4-en-2,6-diyne-1,8-diamine (EDDA) to kill DH5α cells. To trigger Bergman cyclization of EDDA to make diradicals, we used gold nanorods (AuNRs) of chosen dimensions to act as a light-responsive, heat-generating platform. We put EDDA on AuNRs but also left room for polymyxin B nonapeptide (PMBN) to direct the PMBN/EDDA-loaded AuNRs to the surface of DH5α. PMBN interacts specifically with the lipopolysaccharide (LPS) component of the bacterial outer membrane. Importantly, LPS is highly conserved in the family of Gram-negative bacteria. After binding, we use low-power laser light (λ = 785 nm, 69 mW) to activate heat production at the gold metal surface. This heat triggers formation of a reactive 1,4-didehydrobenzene diradical intermediate that can abstract hydrogen atoms from proteins, lipids, and DNA to destroy their function. Transmission electron microscopy (TEM) shows that bifunctional PMBN/EDDA AuNRs are bound to the bacteria and that this interaction is dependent on the rod-to-cell ratio. Upon exposure to light, >85% of DH5α cells are killed according to LIVE/DEAD cell viability assays. The extent of cell death depends on the cell coverage density of bifunctional rods and the duration of exposure to light. Cell viability experiments were also performed in HEPES buffer. HEPES quenched diradical activity, resulting in unharmed cells. Together, our combined approach of photoactivation and EDDA-mediated radical formation demonstrates the potential of using activable enediynes to eliminate Gram-negative bacteria. In future work, it will be important to assess the effectiveness of this approach against other pathogenic organisms.

[This corrects the article DOI: 10.1039/D4SC05396F.].

Using a diverse array of thermally robust phosphine enediyne ligands (dxpeb, X = Ph, Ph-pOCH3, Ph-pCF3, Ph-m2CH3, Ph-m2CF3, iPr, Cy, and tBu) a novel suite of cisplatin-like Pt(ii) metalloenediynes (3, Pt(dxpeb)Cl2) has been synthesized and represents unique electronic perturbations on thermal Bergman cyclization kinetics. Complexes 3e (Ph-m2CF3) and 3f (iPr) are the first of this structure type to be crystallographically characterized with inter alkyne termini distances (3e: 3.13 & Aring;; 3f: 3.10 & Aring;) at the lower end of the widely accepted critical distance range within which enediynes should demonstrate spontaneous ambient temperature cyclization. Despite different electronic profiles, these metalloenediynes adopt a rigid, uniform structure suggesting complexes of the form Pt(dxpeb)Cl2 have orthogonalized geometric and electronic contributions to thermal Bergman cyclization. Kinetic activation parameters determined using 31P NMR spectroscopy highlight the dramatic reactivity and thermal tunability of these complexes. At room temperature, the half-life (t1/2) of cyclization spans a range of similar to 35 hours and for the aryl phosphine derivatives, cycloaromatization rates are 10-30 times faster for complexes with electron donating substituents (3b: Ph-pOCH3; 3d: Ph-m2CH3) compared to those with electron withdrawing substituents (3c: Ph-pCF3; 3e: Ph-m2CF3). Computational interrogation of the aryl phosphine metalloenediynes 3a-3e reveals that the origin of this precise electronic control derives from electronic withdrawing group-mediated alkyne carbon polarization that amplifies coulombic repulsion increasing the cyclization barrier height. Additionally, mixing between the in-plane pi-orbitals and the phosphine aryl ring system is pronounced for complexes with electron donating substituents which stabilizes the developing C-C bond and lowers the activation barrier. This pi-orbital mixing is negligible however, for complexes with electron withdrawing substituents due to an energetic mismatch of the orbital systems. Overall, this work demonstrates that for geometrically rigid frameworks, even remote enediyne functionalization can have pronounced effects on activation barrier.

Introduction:The institutions (i.e., hubs) making up the National Institutes of Health (NIH)-funded network of Clinical and Translational Science Awards (CTSAs) share a mission to turn observations into interventions to improve public health. Recently, the focus of the CTSAs has turned increasingly from translational research (TR) to translational science (TS). The current NIH Funding Opportunity Announcement (PAR-21-293) for CTSAs stipulates that pilot studies funded through the CTSAs must be "focused on understanding a scientific or operational principle underlying a step of the translational process with the goal of developing generalizable solutions to accelerate translational research." This new directive places Pilot Program administrators in the position of arbiters with the task of distinguishing between TR and TS projects. The purpose of this study was to explore the utility of a set of TS principles set forth by NCATS for distinguishing between TR and TS. Methods:Twelve CTSA hubs collaborated to generate a list of Translational Science Principles questions. Twenty-nine Pilot Program administrators used these questions to evaluate 26 CTSA-funded pilot studies. Results:Factor analysis yielded three factors: Generalizability/Efficiency, Disruptive Innovation, and Team Science. The Generalizability/Efficiency factor explained the largest amount of variance in the questions and was significantly able to distinguish between projects that were verified as TS or TR (t = 6.92, p < .001) by an expert panel. Conclusions:The seven questions in this factor may be useful for informing deliberations regarding whether a study addresses a question that aligns with NCATS' vision of TS.

The localized surface plasmon resonance (LSPR) properties of nanocrystals (NCs) allow manipulation of optical responses by controlling their morphology, free carrier density, and local dielectric environment. In this context, semiconductor NCs, in which plasmonic properties arise due to various types of doping, provide unique opportunities in tailoring LSPR properties for a wide range of applications as viable alternatives to expensive noble metal NCs. Although extensive works have been done to control the LSPR properties of semiconductor NCs via doping, the role of surface ligand chemistry in the enhancement of LSPR properties remains poorly understood. Incomplete passivation of surface atoms creates dangling bonds and surface trap states that together could compromise the free carrier density and thus optoelectronic properties. Here, we report the impact of metal-ligand bonding interactions on the free electron density (N-e) and the LSPR response of monoclinic, sub-stoichiometric, and two-dimensional tungsten oxide (WO3-x) nanoplatelets (NPLs). The LSPR properties of WO3-x NPLs arise from the presence of free electrons in the conduction band as a result of oxygen vacancies in the monoclinic crystal. In situ surface passivation of unpurified colloidal WO3-x NPLs with X-type alkylphosphonate (R-PO32-) produces an LSPR peak in the near-infrared region of the electromagnetic spectrum. X-ray photoelectron, electron paramagnetic, and Raman spectroscopic data support the presence of a tridentate PO3-W-3 bonding motif that allows increased passivation of shallow surface trap states, leading to an experimentally determined N-e value of 8.4 X 10(22) cm(-3). Furthermore, experimentally determined bonding characteristics are correlated with density functional theory calculations. The effect of the high N-e values of NPLs on their refractive index sensitivity is also evaluated. Together, the knowledge gained regarding surface-ligand-chemistry-controlled manipulation of the plasmonic properties in semiconducting metal oxide NPLs and the high N-e values of WO3-x NPLs achieved may result in sizable advancement in various LSPR-driven applications such as sensing and energy storage and conversion schemes.

Background Enediynes are anti-cancer agents that are highly cytotoxic due to their propensity for low thermal activation of radical generation. The diradical intermediate produced from Bergman cyclization of the enediyne moiety may induce DNA damage and cell lethality. The cytotoxicity of enediynes and difficulties in controlling their thermal cyclization has limited their clinical use. We recently showed that enediyne toxicity at 37 °C can be mitigated by metallation, but cytotoxic effects of ‘metalloenediynes’ on cultured tumor cells are potentiated by hyperthermia. Reduction of cytotoxicity at normothermia suggests metalloenediynes will have a large therapeutic margin, with cell death occurring primarily in the heated tumor. Based on our previous in vitro findings, FeSO4-PyED, an Fe co-factor complex of (Z)-N,N′-bis[1-pyridin-2-yl-meth-(E)-ylidene]oct-4-ene-2,6-diyne-1,8-diamine, was prioritized for further in vitro and in vivo testing in normal human melanocytes and melanoma cells.Methods Clonogenic survival, apopotosis and DNA binding assays were used to determine mechanisms of enhancement of FeSO4-PyED cytotoxicity by hyperthermia. A murine human melanoma xenograft model was used to assess in vivo efficacy of FeSO4-PyED at 37 or 42.5 °C.Results FeSO4-PyED is a DNA-binding compound. Enhancement of FeSO4-PyED cytotoxicity by hyperthermia in melanoma cells was due to Bergman cyclization, diradical formation, and increased apoptosis. Thermal enhancement, however, was not observed in melanocytes. FeSO4-PyED inhibited tumor growth when melanomas were heated during drug treatment, without inducing normal tissue damage.Conclusion By leveraging the unique thermal activation properties of metalloenediynes, we propose that localized moderate hyperthermia can be used to confine the cytotoxicity of these compounds to tumors, while sparing normal tissue.

Multimetallic architectures that combine chemically diverse materials to affect tandem reactions within a single scaffold drive future nanocatalyst development. Here, we show the unique, interlattice growth of the small molecule activating Ag-0 guest within the Lewis acidic/basic Fe3O4 octahedral host (Fe3O4@Ag-40, 10, 6, 2 at %) via a polyol-hydrothermal procedure. Microscopic (scanning electron microscopy and energy-dispersive X-ray spectroscopy) and structural characterization (powder X-ray diffraction and X-ray photoelectron spectroscopy) of the Fe3O4@Ag hybrid materials reveal doping of Ag-0 in Oh Fe2+ substitutional vacancies of the Fe3O4 host and Ag-0 nanoparticle growth on and embedded deep within (>400 nm, Ar+ sputtering) the octahedra. These hybrid materials activate CO2 and perform C(sp)-H and C(sp(3))-Cl bond scission of alkyne substrates to selectively produce lactone heterocycles in up to 85% yield. Control reactions delineate two distinct pathways for the mechanism involving the complementarity of interfacial sites where alkyne activation occurs at Fe-O sies and CO2 incorporation is predominately managed by Ag-0. The recyclability of the Fe3O4@Ag-40B hybrid catalyst is demonstrated over five cycles and it shows the structural integrity of the octahedra, but a gradual drop in yield of the product from 85 to 45% due to slow depletion of surface Ag NPs is observed. Together, these results illustrate a rare understanding of the cooperative synergy and mechanism of multimetallic nanocatalyst interfaces for multiple substrate reactivity.

Multi-metallic hybrid nancatalysts consisting of a porous metal oxide host and metal satellite guests serve as a scaffold for multi-step transformations of divergent and energy-challenging substrates. Here we have developed a 3D porous MgO framework (Lewis basic host) with Ag0 nanoparticles (noble metal guest) for ambient pressure activation and insertion of CO2 into unsaturated alkyne substrates. The hybrid MgO@Ag-x (x = 2, 5, 7, 8 at % Ag) catalysts are synthesized by impregnating Ag+ ions in porous MgO cubes followed by reduction using NaBH4. Morphological (SEM, TEM, EDX mapping) and structural (PXRD, XPS) characterization reveal that the micron-sized hybrid cubes derive from self-assembly of ~100 nm (edge length) MgO cubes decorated with ~ 5 to 25 nm Ag0 NPs. Detailed XPS analysis illustrates Ag0 is present in two forms, <10 nm NPs and ~25 nm aggregates. The MgO@Ag-7 catalyst is effective for inserting CO2 into aryl alkynes followed by SN2 coupling with allylic chlorides to afford a wide range of ester and lactone heterocycles in excellent yields (61-93%) and with low E-factor (2.8). The proposed mechanism suggests a CO2 capture and substrate assembly role for 3D porous MgO while Ag0 performs the key activation of alkyne and CO2 insertion steps. The catalyst is recyclable (5x) with no significant loss of product yield. Overall, these results demonstrate viable approaches to hybrid catalyst development for challenging conversions such as CO2 utilization in a green and sustainable manner.

Fibrin plays a critical role in wound healing and hemostasis, yet it is also the main case of cardiovascular diseases and thrombosis. Here, we show the unique design of Au-Cu@PANI alloy core-shell rods for fibrin clot degradation. Microscopic (transmission electron microscopy (TEM), scanning transmission electron microscopy-energy-dispersive X-ray (STEM-EDX)) and structural characterizations (powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS)) of the Au-Cu@PANI hybrid material reveal the formation of Au-Cu heterogeneous alloy core rods (aspect ratio = 3.7) with thin Cu2O and PANI shells that create a positive surface charge (ζ-potential = +22 mV). This architecture is supported by the survey XPS spectrum showing the presence of Cu 2p, N 1s, and C 1s features with binding energies of 934.8, 399.7, and 284.8 eV, respectively. Upon photolysis (λ ≥ 495 or 590 nm), these hybrid composite nanorods provide sufficient excited-state redox potential to generate reactive oxygen species (ROS) for degradation of model fibrin clots within 5-7 h. Detailed scanning electron microscopy (SEM) analysis of the fibrin network shows significant morphology modification including formation of large voids and strand termini, indicating degradation of fibrin protofibril by Au-Cu@PANI. The dye 1,3-diphenylisobenzofuran (DPBF) used to detect the presence of 1O2 shows a 27% bleaching of the absorption at λ = 418 nm within 75 min of irradiation of an aqueous Au-Cu@PANI solution in air. Moreover, electron paramagnetic resonance (EPR) spin-trapping experiments reveal a hyperfine-coupled triplet signature at room temperature with intensities 1:1:1: and g-value = 2.0057, characteristic of the reaction between the spin probe 4-Oxo-TEMP and 1O2 during irradiation. Controlled 1O2 scavenging experiments by NaN3 show 82% reduction in the spin-trapped EPR signal area. Both DPBF bleaching and EPR spin trapping indicate that in situ generated 1O2 is responsible for fibrin strand scission. This unique nanomaterial function via use of ubiquitous oxygen as a reagent could open creative avenues for future in vivo biomedical applications to treat fibrin clot diseases.

A suite of lanthanoenediyne complexes of the form Ln(macrocycle)X-3 (Ln = La3+, Ce3+, Gd3+, Tb3+, Lu3+; X = NO3-, Cl-, OTf-) was prepared by utilizing an enediynecontaining [2 + 2] hexaaza-macrocycle (2). The solid-state " Bergman cyclization temperatures, measured via DSC, decrease with the denticity of X (bidentate NO3-, T = 267-292 degrees C; monodentate Cl-, T = 238-262 degrees C; noncoordinating OTf-, T = 170-183 degrees C). C-13 NMR characterization shows that the chemical shifts of the acetylenic carbon atoms also rely on the anion identity. The alkyne carbon closest to the metal binding site, C-A, exhibits a Delta delta > 3 ppm downfield shift, while the more distal alkyne carbon, CB, displays a concomitant Delta delta <= 2.5 ppm upfield shift, reflecting a depolarization of the alkyne on metal inclusion. For all metals studied, the degree of perturbation follows the trend 2 < NO3- < Cl- < OTf-. This belies a greater degree of electronic rearrangement in the coordinated macrocycle as the denticity of X and its accompanying shielding of the metal's Lewis acidity decrease. Computationally modeled structures of LnX(3) show a systematic increase in the lanthanide-2 coordination number (CNLa-mc = 2 (NO3-), 4 (Cl-), 5 (H2O, model for OTf-)) and a decrease in the mean Ln- N bond length (La-N-average = 2.91 angstrom (NO3-), 2.78 angstrom (Cl-), 2.68 angstrom (H2O)), further suggesting that a decrease in the anion coordination number correlates with an increase in the metal macrocycle interaction. Taken together, these data illustrate a Bergman cyclization landscape that is influenced by the bonding of metal to an enediyne ligand but whose reaction barrier is ultimately dominated by the coordinating ability of the accompanying anion.

The predictable and controllable interaction of small organic or peptidic molecules with biological substrates is the primary reason most pharmaceuticals are narrowly decorated carbon frameworks. The inhibition or activation binding models are measurable and without side reactions that can cause pathological angst. Yet many diseases, especially those involving rapid proliferation of cells (i.e., cancer) or aggregation of peptides (e.g., heart disease, Alzheimer's disease) have not yet been cured by inhibition therapeutics. Additionally, interventional medicine is often required to alleviate such maladies by physical removal first, followed by molecular-level therapy as a second stage. Thus, there appears to be a niche for more aggressive therapeutics that may employ harsher chemical processes to realize clinical efficacy, albeit without causing catastrophic side effects. Molecules that may be considered for this challenge are not typically biomimetic, nor do they fit the traditional pharmaceutical paradigm. They may have unusual modes of action or undesired reactivity that can be lethal if not controlled. These are the outliers; potential pharmacophores that biology does not know how to manage or adapt to. This is why they may be an intriguing class of agents that needs continuous development. In this Account, we connect the under-developed enediyne family of compounds and our metalloenediyne derivatives to existing radical-based therapeutics such as bleomycin and doxorubicin to illustrate that controlled diradical reactivity, although an outlier mechanism, has a place in the therapeutic portfolio. This is self-evident in that of the 11 natural product enediynes known, 2 have clinical impact, a strong ratio. We expand on the chemical diversity of potential enediyne constructs and focus on the accessible trigger mechanisms to activate diradical formation as a method to control toxicity. Moreover, we further illustrate how electromagnetic fields can be employed to activate both molecular and larger nanomaterial constructs that carry highly concentrated payloads of reactive reagent. Finally, we describe how controlled diradical reactivity can reach beyond traditional therapeutic targets such as DNA, to peptide aggregates found in blood clots, neural fibrils, and membrane scaffolds. It is our belief that cleverly constructed frameworks with well-designed and controlled activation/reaction schemes can lead to novel therapeutics that can challenge evolving viral and bacterial invaders. From this evangelical perspective, our hope is that the conceptual framework, if not the specific designs in this Account, stimulate the readership to develop out-of-the-box therapeutic designs that may combat resistant disease targets.

Enediyne natural products are a class of compounds that were recognized for their potential as chemotherapeutic agents many years ago, but found to be highly cytotoxic due to their propensity for low thermal activation. Bergman cyclization of the enediyne moiety produces a diradical intermediate, and may subsequently induce DNA damage and account for the extreme cytotoxicity. While difficulties in controlling the thermal cyclization reaction have limited the clinical use of cyclic enediynes, we have previously shown that enediyne activity, and thus toxicity at physiological temperatures can be modulated by metallation of acyclic enediynes. Furthermore, the cytotoxicity of "metalloenediynes" can be potentiated by hyperthermia. In this study, we characterized a suite of novel metallated enediyne motifs that usually induced little or no cytotoxicity when two different human cancer cell lines were treated with the compounds at 37°C, but showed a significant enhancement of cytotoxicity after cells were exposed to moderate hyperthermia during drug treatment. Cultured U-1 melanoma or MDA-231 breast cancer cells were treated with various concentrations of Cu, Fe and Zn complexes of the enediyne (Z)-N,N'-bis[1-pyridyl-2-yl-meth-(E)-ylidene]octa-4-ene-2,6-diyne-1,8-diamine (PyED) and clonogenic survival was assessed to determine the effects of the drugs at 37°C and 42.5°C. Toxicity at 37°C varied for each compound, but hyperthermia potentiated the cytotoxicity of each compound in both cell lines. Cytotoxicity was concentration-, time- and temperature-dependent. Heating cells during drug treatment resulted in enhanced apoptosis, but the role of cell cycle perturbation in the response of the cells to the drugs was less clear. Lastly, we showed that hyperthermia enhanced the number of DNA double-strand breaks (DSBs) induced by the compounds, and inhibited their repair after drug treatment. Thus, thermal enhancement of cytotoxicity may be due, at least in part, to the propensity of the enediyne moiety to induce DSBs, and/or a reduction in DSB repair efficiency. We propose that "tuning" of metalloenediyne toxicity through better-controlled reactivity could have potential clinical utility, since we envision that such compounds could be administered systemically as relatively non-toxic agents, but cytotoxicity could be enhanced in, and confined to a tumor volume when subjected to localized heating.

Enediynes are a highly cytotoxic class of compounds. However, metallation of these compounds may modulate their activation, and thus their cytotoxicity. We previously demonstrated that cytotoxicity of two different metalloenediynes, including (Z)-N,N′-bis[1-pyridyl-2-yl-meth-(E)-ylidene]octa-4-ene-2,6-diyne-1,8-diamine] (PyED), is potentiated when the compounds are administered to HeLa cells during hyperthermia treatment at concentrations that are minimally or not cytotoxic at 37°C. In this study, we further characterized the concentration, time and temperature dependence of cytotoxicity of PyED on human U-1 melanoma cells. We also investigated the potential mechanisms by which PyED cytotoxicity is enhanced during hyperthermia treatment. Cell killing with PyED was dependent on concentration, temperature during treatment and time of exposure. Potentiation of cytotoxicity was observed when cells were treated with PyED at temperatures ≥39.5°C, and enhancement of cell killing increased with temperature and with increasing time at a given temperature. All cells treated with PyED were shown to have DNA damage, but substantially more damage was observed in cells treated with PyED during heating. DNA repair was also inhibited in cells treated with the drug during hyperthermia. Thus, potentiation of PyED cytotoxicity by hyperthermia may be due to enhancement of drug-induced DNA lesions, and/or the inhibition of repair of sublethal DNA damage. While the selective thermal activation of PyED supports the potential clinical utility of metalloenediynes as cancer thermochemotherapeutic agents, therapeutic gain could be optimized by identifying compounds that produce minimal toxicity at 37°C but which become activated and show enhancement of cytotoxicity within a tumor subjected to localized hyperthermic or thermal ablative treatment, or which might act as bifunctional agents. We thus also describe the development and initial characterization of a novel cofactor complex of PyED, platinated PyED (Pt-PyED). Pt-PyED binds to DNA-like cisplatin, and much like PyED, cytotoxicity is greatly enhanced after treatment with the drug at elevated temperatures. However, in contrast to PyED, Pt-PyED is only minimally cytotoxic at 37°C, at concentrations at which cytotoxicity is enhanced by hyperthermia. Further development of cisplatin-based enediynes may result in compounds which, when activated, will possess multiple DNA binding modalities similar to cisplatin, but produce less side effects in tissues at normothermic temperatures.

Environmental impacts of continued CO2 production have led to an increased need for new methods of CO2 removal and energy development. Nanomaterials are of special interest for these applications, because of their unique chemical and physical properties that allow for highly active surfaces. Here, we successfully synthesize AgPd nanodendrite-modified Au nanoprisms in various shapes (nanoprisms, hexagonal nanoplates, and octahedral nano particles) by selective metal deposition. This strategy involves coupling galvanic replacement between Ag layers in Au@Ag core shell nanoprisms and H2PdCl4 with a coreduction process of silver and palladium ions. Synthesis of AgPd nanodendrite-tipped (4.14-11.47 wt % Pd) and-edged (25.25-31.01 wt % Pd) Au nanoparticles can be controlled simply by tuning the concentration of H2PdCl4. More importantly, these multicomponent AgPd nanodendrite-modified Au nanoparticles show exceptional electrocatalytic performance for CO, reduction. AgPd nanodendrite-edged Au nanoprisms show more favorable potentials (-0.18 V vs RHE) than previously reported nanocatalysts for the reduction of CO2 to formate, and exhibit higher faradaic efficiencies (49%) than Au, AupAg, and AgPd nanodendrite-tipped Au nanoprisms in aqueous electrolytes. Moreover, AgPd nanodendrite-modified Au nanoprisms show much higher selectivity and faradaic efficiency for CO2 reduction to CO (85-87%) than Au and Au@Ag nanoprisms (43-64%) in organic electrolytes. The high performance of these particles for CO2 reduction is attributed to the unique structure of AgPd nanodendrite-modified Au nanoprisms and the synergistic effect of Ag having an affinity for CO2, efficient binding of hydrogen at Pd, and Au as a stable, conductive support. In addition, AgPd nanodendrite-edged Au nanoprisms show highly stable catalytic activity during long-term electrolyses (up to 12 h) and repetitive use. These exciting results indicate that AgPd nanodendrite-modified Au nanoparticles are promising for application in CO2 conversion into useful fuels.

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

Significance Pharmaceuticals often act within a lock-and-key model whereby molecules bind their targets nearly irreversibly, either stalling or initiating biological processes. Here, the agent itself performs no chemical transformation on its target but rather triggers an event or cascade. However, unwanted side effects become more likely as the reactivity of these molecules increases. In contrast, molecular compounds may irreversibly damage biological targets using metal-mediated radical chemistry, but controlling the onset and extent of reaction is challenging. Even so, multiple examples of metal-containing or metal-radical paradigms have been used clinically for imaging and chemotherapy. Within this framework we report a class of metal-mediated radical generators that attack DNA, outcompete DNA polymerase, and are cytotoxic in short times and modest concentrations.

Gold nanorods were adhered onto a glass substrate for use as a sustainable, reusable photocatalyst to reduce 4-nitroaniline with sodium borohydride.