Unexpected Periodicity in Cationic Group 5 Initiators for the Ring-Opening Polymerization of Lactones.

ε-Caprolactone (ε-CL) adducts of cationic, amine tris(phenolate)-supported niobium(V) and tantalum(V) ethoxides initiate the ring-opening polymerization of lactones. The Ta(V) species prepared and applied catalytically herein exhibits higher activity in the ring-opening polymerization (ROP) of ε-caprolactone than the previously reported, isostructural Nb(V) complex, contradicting literature comparisons of Nb(V)- and Ta(V)-based protocols. Both systems also initiate the ROP of δ-valerolactone and rac-ß-butyrolactone, kinetic studies confirming retention of higher activity by the Ta congener. Polymerizations of rac-ß-butyrolactone and δ-valerolactone were previously unrealized under Group V- or Ta-mediated conditions, respectively, although the former has afforded only low molecular weight, cyclic poly-3-hydroxybutyrate. Cationic ethoxo-Nb(V) and -Ta(V) δ-valerolactone adducts are also reported, demonstrating the facility of δ-valerolactone as a ligand and the generality of the synthetic method. Both δ-valerolactone-bearing complexes initiate the ROP of ε-caprolactone, δ-valerolactone, and rac-ß-butyrolactone. Accordingly, we have elucidated trends in reactivity and investigated the initiation mechanism for such systems, the insertion event being predicated upon intramolecular nucleophilic attack on the coordinated lactone by the adjacent alkoxide moiety. This mechanism enables quantitative, stoichiometric installation of a single monomer residue distinct from the bulk of the polymer chain, and permits modification of polymer properties via both manipulation of the molecular architecture and tuning of the polymerization kinetics, and thus dispersity, through hitherto inaccessible independent control of the initiation event.

Unusual Regio- and Chemoselectivity in Oxidation of Pyrroles and Indoles Enabled by a Thianthrenium Salt Intermediate.

A dearomative oxidation of pyrroles to Δ3-pyrrol-2-ones is described, which employs a sulfoxide as oxidant, in conjunction with a carboxylic acid anhydride and a Brønsted acid additive. 3-substituted pyrroles undergo regioselective oxidation to give the product isomer in which oxygen has been introduced at the more hindered position. Regioselectivity is rationalized by a proposed mechanism that proceeds by initial thianthrenium introduction at the less-hindered pyrrole α-position, followed by distal attack of an oxygen nucleophile and subsequent elimination of thianthrene. The same reaction conditions are also able to effect a chemoselective oxidation of indoles to indolin-3-ones and additionally of indolin-3-ones to 2-hydroxyindolin-3-ones. Here again, the regio- and chemoselectivities are rationalized through the intermediacy of a thianthrenium salt.

Rim-Based Binding of Perfluorinated Acids to Pillararenes Purifies Water.

Per- and polyfluoroalkyl substances (PFAS) pose a rapidly increasing global problem as their widespread use and high stability lead worldwide to water contamination, with significant detrimental health effects.[1] Supramolecular chemistry has been invoked to develop materials geared towards the specific capture of PFAS from water,[2] to reduce the concentration below advisory safety limits (e.g., 70 ng/L for the sum of perfluorooctane sulfonic acid, PFOS and perfluorooctanoic acid, PFOA). Scale-up and use in natural waters with high PFAS concentrations has hitherto posed a problem. Here we report a new type of host-guest interaction between deca-ammonium-functionalized pillar[5]arenes (DAF-P5s) and perfluoroalkyl acids. DAF-P5 complexes show an unprecedented 1 : 10 stoichiometry, as confirmed by isothermal calorimetry and X-ray crystallographic studies, and high binding constants (up to 106 M-1) to various polyfluoroalkyl acids. In addition, non-fluorinated acids do not hamper this process significantly. Immobilization of DAF-P5s allows a simple single-time filtration of PFAS-contaminated water to reduce the PFOS/PFOA concentration 106 times to 15-50 ng/L level. The effective and fast (<5 min) orthogonal binding to organic molecules without involvement of fluorinated supramolecular hosts, high breakthrough capacity (90 mg/g), and robust performance (>10 regeneration cycles without decrease in performance) set a new benchmark in PFAS-absorbing materials.

BINOL as a Chiral Solvating Agent for Sulfiniminoboronic Acids.

1H NMR spectroscopic studies using BINOL as a chiral solvating agent (CSA) for a scalemic sulfiniminoboronic acid (SIBA) have revealed concentration- and enantiopurity-dependent variations in the chemical shifts of diagnostic imine protons used to determine enantiopurity levels. 11B/15N NMR spectroscopic studies and X-ray structural investigations revealed that unlike other iminoboronate species, BINOL-SIBA assemblies do not contain N-B coordination bonds, with 1H NMR NOESY experiments indicating that intermolecular H-bonding networks between BINOL and the SIBA analyte are responsible for these variations. These effects can lead to diastereomeric signal overlap at certain er values that could potentially lead to enantiopurity/configuration misassignments. Consequently, it is recommended that hydrogen-bonding-CSA-based 1H NMR protocols should be repeated using both CSA enantiomers to ensure that any concentration- and/or er-dependent variations in diagnostic chemical shifts are accounted for when determining the enantiopurity of a scalemic analyte.

Synthesis of N-alkoxycarbonyl Pyrroles from O-Substituted Carbamates: A Synthetically Enabling Pyrrole Protection Strategy.

The condensation of readily available O-substituted carbamates with 2,5-dimethoxytetrahydrofuran gives N-alkoxycarbonyl pyrroles in a single step and in good yield. By this method, several common amine protecting groups can be introduced on the pyrrole nitrogen. With the exception of N-Boc, N-alkoxycarbonyl groups have seen only minimal use for protection of the pyrrole nitrogen to date. Here, we show that N-alkoxycarbonyl protection can endow pyrrole with distinct reactivity in comparison with N-sulfonyl protection, for example, in a pyrrole acylation protocol employing carboxylic acids with a sulfonic acid anhydride activator.

Synthesis, Structure, and Reactivity of Magnesium Pentalenides.

The first magnesium pentalenide complexes have been synthesized via deprotonative metalation of 1,3,4,6-tetraphenyldihydropentalene (Ph4PnH2) with magnesium alkyls. Both the nature of the metalating agent and the reaction solvent influenced the structure of the resulting complexes, and an equilibrium between Mg[Ph4Pn] and [nBuMg]2[Ph4Pn] was found to exist and investigated by NMR, XRD, and UV-vis spectroscopic techniques. Studies on the reactivity of Mg[Ph4Pn] with water, methyl iodide, and trimethylsilylchloride revealed that the [Ph4Pn]2- unit undergoes electrophilic addition at 1,5-positions instead of 1,4-positions known for the unsubstituted pentalenide, Pn2-, highlighting the electronic influence of the four aryl substituents on the pentalenide core. The ratio of syn/anti addition was found to be dependent on the size of the incoming electrophile, with methylation yielding a 60:40 mixture, while silylation yielded exclusively the anti-isomer.

Approach to Di/Triorganotin(IV) Cations via Hydrolysis of Stannate Salts Bearing Alkanesulfonate Ligands.

An in-depth study of the class of organotin cations bearing weakly coordinating trifluoromethanesulfonate/arylsulfonate has led to key insights into their stability, structural aspects, and role as catalysts. Related chemistry with alkanesulfonate ligands remains a missing link due to the strong Sn-O bond. The study reported herein describes the scope of diorganostannates, [n-Bu4N][R2Sn(OSO2R1)3] (R = n-Bu, R1 = Me(1), Et(2); R = Ph, R1 = Me(3)), as reactive substrates in the presence of adventitious water to afford [n-Bu2SnOH(OSO2Me)] (4), [n-Bu2Sn(H2O)4][n-Bu4N][OSO2Et]3·H2O (5), and [Ph2Sn(H2O)4][n-Bu4N]2[OSO2Me]4 (6), respectively, the latter two being the first examples of salt cocrystals comprising tetra(aqua)diorganotin cations. Hydrolysis of 3 in the presence of 1,4-bis((1H-imidazol-1-yl)methyl)benzene (bix) as the N-donor ligand proceeds via disproportionation and yields [Ph3Sn(bix)](OSO2Me) (7) along with an insoluble solid, likely derived from the hydrolysis of PhSn(OSO2Me)3. Direct evidence of this phenomenon can be gleaned from ESI-MS of 3, which identifies mass clusters corresponding to [Ph3Sn(OSO2Me)2]- and [PhSn(OSO2Me)3-H+]-. X-ray crystallographic studies of 1-7 are reported to establish their structural identity and the role of alkanesulfonate anions in the formation of supramolecular assemblies.

Lithium, Tin(II), and Zinc Amino-Boryloxy Complexes: Synthesis and Characterization.

Analogous to the ubiquitous alkoxide ligand, metal boroxide and boryloxy complexes are an underexplored class of hard anionic O- ligand. A new series of amine-stabilized Li, Sn(II), and Zn boryloxy complexes, comprising electron-rich tetrahedral boron centers have been synthesized and characterized. All complexes have been characterized by one-dimensional (1D), two-dimensional (2D), and DOSY NMR, which are consistent with the solid-state structures unambiguously determined via single-crystal X-ray diffraction. Electron-rich µ2- (Sn and Zn) and µ3- (Li) boryloxy binding modes are observed. Compounds 6-9 are the first complexes of this class, with the chelating bis- and tris-phenol ligands providing a scaffold that can be easily functionalized and provides access to the boronic acid pro-ligand, hence allowing facile direct synthesis of the resulting compounds. Computational quantum chemical studies suggest a significant enhancement of the π-donor ability of the amine-stabilized boryloxy ligand because of electron donation from the amine functionality into the p-orbital of the boron atom.

Coordination of ε-Caprolactone to a Cationic Niobium(V) Alkoxide Complex: Fundamental Insight into Ring-Opening Polymerization via Coordination-Insertion.

We report three niobium-based initiators for the catalytic ring-opening polymerization (ROP) of ε-caprolactone, exhibiting good activity and molecular weight control. In particular, we have prepared on the gram-scale and fully characterized a monometallic cationic alkoxo-Nb(V) ε-caprolactone adduct representing, to the best of our knowledge, an unprecedented example of a metal complex with an intact lactone monomer and a functional ROP-initiating group simultaneously coordinated at the metal center. At 80 °C, all three systems initiate the immortal solution-state ROP of ε-caprolactone via a coordination-insertion mechanism, which has been confirmed through experimental studies, and is supported by computational data. Natural bond orbital calculations further indicate that polymerization may necessitate isomerization about the metal center between the alkoxide chain and the coordinated monomer. The observations made in this work are expected to inform mechanistic understanding both of amine tris(phenolate)-supported metal alkoxide ROP initiators, including various highly stereoselective systems for the polymerization of lactides and of coordination-insertion-type ROP protocols more broadly.

Persistent azulene α-carbocations: synthesis from aldehydes, spectroscopic and crystallographic properties.

The non-benzenoid aromatic system azulene is sufficiently nucleophilic at C1 that it can react with a protonated aldehyde to form an α-azulenyl alcohol. This in turn may be protonated and undergo loss of water to give an azulene α-carbocation. We report the isolation of such azulenyl cations as salts with non-coordinating anions. The salts have been characterised by NMR, UV/Vis absorption and (in certain cases) X-ray crystallography. Reduction of representative salts to afford azulenyl(aryl) methylenes has been demonstrated.

Pd(II)-Mediated C-H Activation for Cysteine Bioconjugation.

Selective bioconjugation remains a significant challenge for the synthetic chemist due to the stringent reaction conditions required by biomolecules coupled with their high degree of functionality. The current trailblazer of transition-metal mediated bioconjugation chemistry involves the use of Pd(II) complexes prepared via an oxidative addition process. Herein, the preparation of Pd(II) complexes for cysteine bioconjugation via a facile C-H activation process is reported. These complexes show bioconjugation efficiency competitive with what is seen in the current literature, with a user-friendly synthesis, common Pd(II) sources, and a more cost-effective ligand. Furthermore, these complexes need not be isolated, and still achieve high conversion efficiency and selectivity of a model peptide. These complexes also demonstrate the ability to selectively arylate a single surface cysteine residue on a model protein substrate, further demonstrating their utility.

Charge transfer modulation in charge transfer co-crystals driven by crystal structure morphology.

The electronic properties of a charge-transfer (donor-acceptor) semiconducting organic co-crystal, Perylene:F4-TCNQ (PE:F4) (the donor, D, is PE and the acceptor, A, is 2,3,5,6-tetrafluoro-7,7,8,8 tetracyanoquinodimethane (F4)) in its 3 : 2 stoichiometry, are experimentally and theoretically studied. This is performed by means of electron paramagnetic resonance (EPR) and solid state electrochemical techniques, such as cyclic voltammetry (CV) measurements on single crystals. In particular, solid state electrochemistry proves to be an effective tool to probe, on a macroscopic scale, the electronic characteristics of the co-crystal. However, EPR highlights the presence of spin ½ radicals localized on F4 molecules, possibly linked to defects. The experimental findings are discussed on the basis of density functional theory (DFT) based calculations, carried out using both the projector augmented wave (PAW), with "periodic boundary conditions" (pbc), method and the localized orbitals, molecular cluster, approach. In particular, a satisfying agreement is found between the experimental, 0.336 eV (electrochemical), and theoretical, 0.303 eV (PAW), band gaps. Differences with the reported optical bandgap are discussed considering excitonic effects.

Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines.

Catalytic, intermolecular hydroaminoalkylation (HAA) of styrenes provides a powerful disconnection for pharmacologically relevant γ-arylamines, but current methods cannot utilize unprotected primary alkylamines as feedstocks. Metal-catalyzed HAA protocols are also highly sensitive to α-substitution on the amine partner, and no catalytic solutions exist for α-tertiary γ-arylamine synthesis via this approach. We report a solution to these problems using organophotoredox catalysis, enabling a direct, modular, and sustainable preparation of α-(di)substituted γ-arylamines, including challenging electron-neutral and moderately electron-rich aryl groups. A broad range of functionalities are tolerated, and the reactions can be run on multigram scale in continuous flow. The method is applied to a concise, protecting-group-free synthesis of the blockbuster drug Fingolimod, as well as a phosphonate mimic of its in vivo active form (by iterative α-C-H functionalization of ethanolamine). The reaction can also be sequenced with an intramolecular N-arylation to provide a general and modular access to valuable (spirocyclic) 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydronaphthyridines. Mechanistic and kinetic studies support an irreversible hydrogen atom transfer activation of the alkylamine by the azidyl radical and some contribution from a radical chain. The reaction is photon-limited and exhibits a zero-order dependence on amine, azide, and photocatalyst, with a first-order dependence on styrene.

Structural Investigations, Cellular Imaging, and Radiolabeling of Neutral, Polycationic, and Polyanionic Functional Metalloporphyrin Conjugates.

Over the past decade, porphyrin derivatives have emerged as invaluable synthetic building blocks and theranostic kits for the delivery of cellular fluorescence imaging and photodynamic therapy. Tetraphenylporphyrin (TPP), its metal complexes, and related derivatives have been investigated for their use as dyes in histology and as components of multimodal imaging probes. The photophysical properties of porphyrin-metal complexes featuring radiometals have been a focus of our attention for the realization of fluorescence imaging probes coupled with radioimaging capabilities and therapeutic potential having "true" theranostic promise. We report hereby on the synthesis, radiochemistry, structural investigations, and preliminary in vitro and in vivo uptake studies on a range of functionalized porphyrin-based derivatives. In pursuit of developing new porphyrin-based probes for multimodality imaging applications, we report new functionalized neutral, polycationic, and polyanionic porphyrins incorporating nitroimidazole and sulfonamide moieties, which were used as targeting groups to improve the notoriously poor pharmacokinetics of porphyrin tags. The resulting functional metalloporphyrin species were stable under serum challenges and the nitroimidazole and sulfonamide derivatives remained fluorescent, allowing in vitro confocal studies and visualization of the lysosomal uptake in a gallium(III) sulfonamide derivative. The molecular structures of selected porphyrin derivatives were determined by single crystal X-ray diffraction using synchrotron radiation. We also investigated the nature of the emission/excitation behavior of model functional porphyrins using in silico approaches such as TD DFT in simple solvation models. The conjugation of porphyrins with the [7-13] and [7-14] fragments of bombesin was also achieved, to provide targeting of the gastrin releasing peptide receptor (GRPR). Depending on the metal, probe conjugates of relevance for single photon emission computed tomography (SPECT) or positron emission tomography (PET) probes have been designed and tested hereby, using TPP and related functional free base porphyrins as the bifunctional chelator synthetic scaffold and 111In[In] or 68Ga[Ga], respectively, as the central metal ions. Interestingly, for simple porphyrin conjugates good radiochemical incorporation was obtained for both radiometals, but the presence of peptides significantly diminished the radio-incorporation yields. Although the gallium-68 radiochemistry of the bombesin conjugates did not show radiochemical incorporation suitable for in vivo studies, likely because the presence of the peptide changed the behavior of the TPP-NH2 synthon taken alone, the optical imaging assays indicated that the conjugated peptide tags do mediate uptake of the porphyrin units into cells.

C4-aldehyde of guaiazulene: synthesis and derivatisation.

Guaiazulene is an alkyl-substituted azulene available from natural sources and is a much lower cost starting material for the synthesis of azulene derivatives than azulene itself. Here we report an approach for the selective functionalisation of guaiazulene which takes advantage of the acidity of the protons on the guaiazulene C4 methyl group. The aldehyde produced by this approach constitutes a building block for the construction of azulenes substituted on the seven-membered ring. Derivatives of this aldehyde synthesised by alkenylation, reduction and condensation are reported, and the halochromic properties of a subset of these derivatives have been studied.

Colorimetric detection of Hg2+ with an azulene-containing chemodosimeter via dithioacetal hydrolysis.

Azulene is a bicyclic aromatic chromophore that absorbs in the visible region. Its absorption maximum undergoes a hypsochromic shift if a conjugated electron-withdrawing group is introduced at the C1 position. This fact can be exploited in the design of a colorimetric chemodosimeter that functions by the transformation of a dithioacetal to the corresponding aldehyde upon exposure to Hg2+ ions. This chemodosimeter exhibits good chemoselectivity over other metal cations, and responds with an unambiguous colour change clearly visible to the naked eye. Its synthesis is concise and its ease of use makes it appropriate in resource-constrained environments, for example in determing mercury content of drinking water sources in the developing world.

Divergent Catalytic Strategies for the Cis/Trans Stereoselective Ring-Opening Polymerization of a Dual Cyclic Carbonate/Olefin Monomer.

A dual seven-membered cyclic carbonate/olefin monomer was synthesized from CO2 and cis-1,4-butenediol and polymerized. The properties of the polymer were controlled using divergent catalytic strategies toward the stereochemistry of the olefin. Ring-opening polymerization of the cyclic carbonate using an organocatalytic approach retained the cis-stereoconfiguration of the olefin and yielded a hard semicrystalline polymer (Tm 115 °C). Ring-opening metathesis polymerization using Grubbs' catalyst proceeded with high trans-stereoregularity (95%) and produced a soft amorphous polymer (Tg -22 °C). Cis to trans isomerization of the polymer was possible using Cu(I) salts under UV light. In all polymers, the C═C double bond remained available for postpolymerization modification and thermoset resins were formed by cross-linking. From this single monomer, cis-trans-cis triblock copolymers, with potential applications as thermoplastic elastomers, were synthesized by combining both strategies using cis-1,4-butenediol as a chain transfer agent.

Azulene-Derived Fluorescent Probe for Bioimaging: Detection of Reactive Oxygen and Nitrogen Species by Two-Photon Microscopy.

Two-photon fluorescence microscopy has become an indispensable technique for cellular imaging. Whereas most two-photon fluorescent probes rely on well-known fluorophores, here we report a new fluorophore for bioimaging, namely azulene. A chemodosimeter, comprising a boronate ester receptor motif conjugated to an appropriately substituted azulene, is shown to be an effective two-photon fluorescent probe for reactive oxygen species, showing good cell penetration, high selectivity for peroxynitrite, no cytotoxicity, and excellent photostability.

Tailoring Structural Diversity in Dimethyltin Carboxylates by the pH-Controlled Hydrothermal Approach.

The study presents a rational synthesis of new dimethyltin carboxylates, Me2Sn(H2btec) (1), Me2Sn(btec)0.5(2), [Me2Sn(H2O)2(btec)0.5]·H2O (3), and [{Me2SnOSn(OH)Me2}(Me2SnOH)(btec)0.5]·H2O (4), derived from tetratopic 1,2,4,5-benzenetetracarboxylic acid (H4btec). The method relies upon hydrothermal reaction (130 °C, 72 h) of dimethyltin dichloride and H4btec under optimized pH (2 < pH < 8) conditions that allow control over dimethyltin speciation in aqueous medium as well as degree of deprotonation of the tetrafuntional carboxylic acid. The formation of a three-dimensional assembly in 1 is assisted by the bridging bidentate (µ2) mode of the carboxylate and O-H···O hydrogen bonds involving -COOH groups. The structure represents a unique example of the diorganotin framework derived from a partially deprotonated polyfuntional carboxylic acid. The structure of 2 adopts a three-dimensional motif wherein each pair of µ2-carboxylate groups (designated by C1 and C4) of the tetraanionic ligand form different spatial arrangements. For 3, the formation of one-dimensional motif with eight-coordinated tin atoms is assisted by the anisobidentate character of the carboxylate groups. The structure of 4 includes linear chains comprised of [Me2Sn(µ2-OH)]2 and the carboxylate ligand which extend to a layered motif with symmetrically substituted ladder-like distannoxanes acting as linkers. The underlying nets of 1, 2, and 4 exhibit sqc11, scu(sqc170), and sql topologies, respectively. Notably, these assemblies are extremely robust and show no sign of degradation upon exposure to neutral as well as weakly acidic/basic aqueous medium for 7 days.

Aerosol-Assisted Chemical Vapor Deposition of ZnS from Thioureide Single Source Precursors.

A family of 12 zinc(II) thoureide complexes, of the general form [{L}ZnMe], [{L}Zn{N(SiMe3)2}], and [{L}2Zn], have been synthesized by direct reaction of the thiourea pro-ligands iPrN(H)CS(NMe2) H[L1], CyN(H)CS(NMe2) H[L3], tBuN(H)CS(NMe2) H[L2], and MesN(H)CS(NMe2) H[L4] with either ZnMe2 (1:1) or Zn{N(SiMe3)2}2 (1:1 and 2:1) and characterized by elemental analysis, NMR spectroscopy, and thermogravimetric analysis (TGA). The molecular structures of complexes [{L1}ZnMe]2 (1), [{L2}ZnMe]2] (2), [{L3}ZnMe]∞ (3), [{L4}ZnMe]2] (4), [{L1}Zn{N(SiMe3)2}]2 (5), [{L2}Zn{N(SiMe3)2}]2 (6), [{L3}Zn{N(SiMe3)2}]2] (7), [{L4}Zn{N(SiMe3)2}]2] (8), [{L1}2Zn]2 (9), and [{L4}2Zn]2 (12) have been unambiguously determined using single crystal X-ray diffraction studies. Thermogravimetric analysis has been used to assess the viability of complexes 1-12 as single source precursors for the formation of ZnS. On the basis of TGA data compound 9 was investigated for its utility as a single source precursor to deposit ZnS films on silica-coated glass and crystalline silicon substrates at 150, 200, 250, and 300 °C using an aerosol assisted chemical vapor deposition (AACVD) method. The resultant films were confirmed to be hexagonal-ZnS by Raman spectroscopy and PXRD, and the surface morphologies were examined by SEM and AFM analysis. Thin films deposited from (9) at 250 and 300 °C were found to be comprised of more densely packed and more highly crystalline ZnS than films deposited at lower temperatures. The electronic properties of the ZnS thin films were deduced by UV-Vis spectroscopy to be very similar and displayed absorption behavior and band gap (Eg = 3.711-3.772 eV) values between those expected for bulk cubic-ZnS (Eg = 3.54 eV) and hexagonal-ZnS (Eg = 3.91 eV).