Atom‐Economic,Regiodivergent, and Stereoselective Coupling of Imidazole Derivatives with Terminal Allenes

New Rh‐ and Pd‐catalyzed regiodivergent and stereoselective intermolecular coupling reactions of imidazole derivatives with mono‐substituted allenes are herein reported. Using a Rh^I/Josiphos system, perfect regioselectivities and high enantiomeric excess were obtained, while a Pd^II/dppf system gave linear products with high regioselectivities and high E/Z selectivities. This method permits the atom economic synthesis of valuable branched and linear allylic imidazole derivatives.     

A Deadly Organometallic Luminescent Probe: Anticancer Activity of a ReI Bisquinoline Complex

The photophysical properties of [Re(CO)₃(L ‐N₃)]Br (L ‐N₃=2‐azido‐N,N‐bis[(quinolin‐2‐yl)methyl]ethanamine), which could not be localized in cancer cells by fluorescence microscopy, have been revisited in order to evaluate its use as a luminescent probe in a biological environment. The Re^I complex displays concentration‐dependent residual fluorescence besides the expected phosphorescence, and the nature of the emitting excited states have been evaluated by DFT and time‐dependent (TD) DFT methods. The results show that fluorescence occurs from a ¹LC/MLCT state, whereas phosphorescence mainly stems from a ³LC state, in contrast to previous assignments. We found that our luminescent probe, [Re(CO)₃(L ‐N₃)]Br, exhibits an interesting cytotoxic activity in the low micromolar range in various cancer cell lines. Several biochemical assays were performed to unveil the cytotoxic mechanism of the organometallic Re^I bisquinoline complex. [Re(CO)₃(L ‐N₃)]Br was found to be stable in human plasma indicating that [Re(CO)₃(L ‐N₃)]Br itself and not a decomposition product is responsible for the observed cytotoxicity. Addition of [Re(CO)₃(L ‐N₃)]Br to MCF‐7 breast cancer cells grown on a biosensor chip micro‐bioreactor immediately led to reduced cellular respiration and increased glycolysis, indicating a large shift in cellular metabolism and inhibition of mitochondrial activity. Further analysis of respiration of isolated mitochondria clearly showed that mitochondrial respiratory activity was a direct target of [Re(CO)₃(L ‐N₃)]Br and involved two modes of action, namely increased respiration at lower concentrations, potentially through increased proton transport through the inner mitochondrial membrane, and efficient blocking of respiration at higher concentrations. Thus, we believe that the direct targeting of mitochondria in cells by [Re(CO)₃(L ‐N₃)]Br is responsible for the anticancer activity.     

Tuning Thiophene with Phosphorus: Synthesis and Electronic Properties of Benzobisthiaphospholes

1,4‐Dimercapto‐2,5‐diphosphinobenzene and 3,6‐bis(hexyloxy)‐1,4‐dimercapto‐2,5‐diphosphinobenzene were synthesized and combined with various acid chlorides to obtain a series of benzobisthiaphospholes. Electrochemical and photophysical properties of the substituted benzobisthiaphospholes have been evaluated, and the observed reductions are more facile than the related benzothiaphospholes and 2,6‐diphenylbenzobisthiazole. A benzobisthiaphosphole with C₆H₄‐p‐CN substituents was reduced at E_1/2=?1.08 V (vs. saturated calomel electrode (SCE)). X‐ray diffraction data for several of these phosphorus heterocycles has been obtained, and DFT calculations at the B3LYP level have been performed.     

Hydroxymethylated Phyllobilins: A Puzzling New Feature of the Dioxobilin Branch of Chlorophyll Breakdown

Colorless nonfluorescent chlorophyll (Chl) catabolites (NCCs) are formyloxobilin‐type phyllobilins, which are considered the typical products of Chl breakdown in senescent leaves. However, in degreened leaves of some plants, dioxobilin‐type Chl catabolites (DCCs) predominate, which lack the formyl group of the NCCs, and which arise from Chl catabolites by oxidative removal of the formyl group by a P450 enzyme. Here a structural investigation of the DCCs in the methylesterase16 mutant of Arabidopsis thaliana is reported. Eight new DCCs were identified and characterized structurally. Strikingly, three of these DCCs carry stereospecifically added hydroxymethyl groups, and represent bilin‐type linear tetrapyrroles with an unprecedented modification. Indeed, DCCs show a remarkable structural parallel, otherwise, to the bilins from heme breakdown.     

How Many Molecules are Required to Obtain a Steady Faradaic Current from Mediated Electron Transfer at a Single Nanoparticle on a Supporting Surface?

We investigate the chronoamperometric noise characteristics of electron‐transfer reactions occurring on single nanoparticles (NPs) and assemblies of well‐separated NPs on a supporting surface. To this end, we combine a formerly described expression for the steady‐state current of a single particle with the shot‐noise model and derive an expression for the signal‐to‐noise ratio as a function of bulk concentration and particle radius. Our findings are supported by random‐walk simulations, which closely match the analytical results.     

Replacement of the Cobalt Center of Vitamin B12 by Nickel: Nibalamin and Nibyric Acid Prepared from Metal-Free B12 Ligands Hydrogenobalamin and Hydrogenobyric Acid

The (formal) replacement of Co in cobalamin ( Cbl ) by Ni^II generates nibalamin ( Nibl ), a new transition-metal analogue of vitamin B₁₂. Described here is Nibl , synthesized by incorporation of a Ni^II ion into the metal-free B₁₂ ligand hydrogenobalamin ( Hbl ), itself prepared from hydrogenobyric acid ( Hby ). The related Ni^II corrin nibyric acid ( Niby ) was similarly synthesized from Hby , the metal-free cobyric acid ligand. The solution structures of Hbl , and Niby and Nibl , were characterized by spectroscopic studies. Hbl features two inner protons bound at N2 and N4 of the corrin ligand, as discovered in Hby . X-ray analysis of Niby shows the structural adaptation of the corrin ligand to Ni^II ions and the coordination behavior of Ni^II. The diamagnetic Niby and Nibl , and corresponding isoelectronic Co^I corrins, were deduced to be isostructural. Nibl is a structural mimic of four-coordinate base-off Cbls , as verified by its ability to act as a strong inhibitor of bacterial adenosyltransferase.     

CO2 to CO: Photo- and Electrocatalytic Conversion Based on Re(I) Bis-Arene Frameworks: Synergisms Between Catalytic Subunits

Reduction of CO₂ to CO and H₂O is a two electron/two proton process. For this process, multinuclear complexes offer advantages by concentrating reduction equivalents more efficiently than mononuclear systems. We present novel complexes with [Re(η⁶-C₆H₆)₂]⁺ as scaffold conjugated to one or two catalytically active [Ru(dmbpy)(CO)₂Cl₂] subunits (dmbpy=5,5′-dimethyl-2,2′-bipyridine). The [Re(η⁶-C₆H₆)₂]⁺ scaffold was chosen due to its very high photo- and chemical stability, as well as the multiple degrees of freedom it offers for any conjugated functionalities. High efficiency and selectivity for the reduction of CO₂ to CO (over H₂ or HCOOH) is reported. TONs and TOFs were found to be comparable or higher than for the catalyst subunit without the rhenium framework. Cooperativity in photo- and electrocatalysis is observed for the complex comprising two catalytic subunits. The synergistic communication between the two catalytic subunits is responsible for the observed enhancement in both photo- and electrocatalytic performance. Confirmation of electronic communication between the two [Ru(dmbpy)(CO)₂Cl₂] subunits as well as the elucidation of a possible mechanism was supported by electrochemistry, IR-spectroelectrochemistry and DFT studies.     

Adjuvants that Empower the Action of Photodynamic Therapy

Compounds have been devised whose supportive actions make them important adjuvants in the priming of photosensitization to selectively target cancer cells. Here, we highlight the paper by Maytin and Hasan in this issue of Photochemistry & Photobiology, which describes adjuvants methotrexate, 5-fluorouracil, vitamin D and its analogs leading to improved photodynamic therapy outcome. These small molecule adjuvants act by different mechanisms to enhance the cytotoxicity in tumor cells and the therapeutic effect in cancers. These findings add to the list of strategies for enhancement of photodynamic therapy.     

About the Reaction of C(PPh3)2 with [M(CO)6] (M = Cr,Mo): Unusual Formation of μ-Carbonato Complexes of Mo under Participation of THF

Attempts to synthesize complexes of group 6 carbonyl compounds [M(CO)₆] (M = Cr, Mo, W) with the carbone C(PPh₃)₂ ( 1 ) via the photo chemically created adducts [(CO)₅M(THF)] lead to quantitative formation of the salts [HC(PPh₃)₂]₂[M₂(CO)₁₀] ( 2 , Cr; 3 , Mo; 4 , W). Alternatively, a long-time thermal reaction of [Mo(CO)₆] performed with 1 in THF generates a series of products initiated by a Wittig-type reaction. In addition to 3 , minor amounts of [(CO)₅MoCCPPh₃] ( 8 ), [(CO)₅MoO₂CC{PPh₃}₂] ( 5 ), and the carbonate complexes [HC(PPh₃)₂]₂[(CO)₅Mo(CO₃)Mo(CO)₄] ( 6 ) and [HC(PPh₃)₂]₂[(CO)₄Mo(CO₃)Mo(CO)₄] ( 7 ) were found. Compounds 2 , 3 , 5 , 6 , and 7 were characterized by X-ray analyses, ³¹P NMR, and IR spectroscopy. The water, necessary for the formation of the carbonate, stems from decomposition of THF.     

Synthesis of Small‐Molecule Fluorescent Probes for the In Vitro Imaging of Calcium‐Activated Potassium Channel KCa3.1

Small‐molecule probes for the in vitro imaging of K_Ca3.1 channel‐expressing cells were developed. Senicapoc, showing high affinity and selectivity for the K_Ca3.1 channels, was chosen as the targeting component. BODIPY dyes 15 – 20 were synthesized and connected by a Cu^I‐catalyzed azide–alkyne [3+2]cycloaddition with propargyl ether senicapoc derivative 8 , yielding fluorescently labeled ligands 21 – 26 . The dimethylpyrrole‐based imaging probes 25 and 26 allow staining of K_Ca3.1 channels in NSCLC cells. The specificity was shown by removing the punctate staining pattern by pre‐incubation with senicapoc. The density of K_Ca3.1 channels detected with 25 and by immunostaining was identical. The punctate structure of the labeled channels could also be observed in living cells. Molecular modeling showed binding of the senicapoc‐targeting component towards the binding site within the ion channel and orientation of the linker with the dye along the inner surface of the ion channel.