Reversible Photooxygenation of Anthracene Carboxyimide for Singlet Oxygen Formation: Mechanistic Study and Efficient Nitrite Detection.

Polycyclic aromatic endoperoxides are important sources of singlet oxygen (1 O2 ) and their formation from polyacenes is well established. Anthracene carboxyimides are of particular interest as they exhibit excellent antitumor activity and possess unique photochemical properties. However, the photooxygenation of the synthetically versatile anthracene carboxyimide moiety has not been reported due to its competing [4+4] photodimerization reaction. Herein, we describe the reversible photo-oxidation of an anthracene carboxyimide. X-ray crystallographic analysis surprisingly revealed the formation of a racemic mixture of chiral hydroperoxides, rather than the expected endoperoxide. The photoproduct undergoes both photo- and thermolysis to form 1 O2 . Activation parameters were derived for the thermolysis and the mechanisms of photooxygenation and thermolysis are discussed. The anthracene carboxyimide also showed high selectivity and sensitivity for nitrite anions in acidic aqueous media and possessed stimuli-responsive behaviour.

Propeller, Linear, Cruciform and Stellate Spiro-bicarbazolium Salts.

A general synthetic approach to halogenated tetraaryl-ammonium salts has been developed and illustrated crystallographically. Bromide ammonium salts used as common synthetic intermediates together with Suzuki coupling of these bromides to a family of boronic acids provided a simplified strategy for arylation. Resolution of the C2 subset of spiro-bicarbazolium derivatives led to the first examples of enantiopure spiro-bicarbazoliums and the assignment of their absolute configuration by comparison of computational and experimental electronic circular dichroism (ECD) spectra. An ECD comparison with Prelog's spirobifluorenes is provided. The absolute configuration of the meta-bromide spiro-bicarbazolium salt was confirmed by anomalous scattering. Cruciform and stellate tetra-substituted salts provide a test of the limits of the methodology, and their structures suggest them to be candidates for MOF building blocks.

Cooperative Weak Dispersive Interactions Actuate Catalysis in a Shape-Selective Abiological Racemase.

A simple abiological host-guest system demonstrates racemase activity with catalytic rate enhancements of 104 without employing traditional functional groups. Cooperative weak interactions enhanced through shape-complementarity between the catalyst active site and the reaction transition state drive this activity, as proposed by Pauling for enzymes. In analogy to the Jencks' concept of catalytic antibodies, it is shown that a hapten resembling the planar transition state of the bowl inversion acts as a potent inhibitor of this catalytic process. In contrast, no substrate/product inhibition is detected, and a relatively weak binding of the substrate is observed (Ka ≈ 102 M-1 at 293 K). This simple box-and-bowl system demonstrates that shape selectivity arising from cooperative dispersive forces suffices for the emergence of a catalytic system with an enzyme-like thermodynamic profile.

Enantiopure C5 Pentaindenocorannulenes: Chiral Graphenoid Materials.

Chiral carbon nanomaterials offer numerous prospects for material science. As a fundamental building block for non-planar graphenoid materials, pentaindenocorannulene (PIC) with its C5v symmetrical structure presents a platform for creation of supramolecular chiral carbon materials. Specifically, when uniformly penta-substituted on its periphery, PIC generates C5 symmetrical chiral buckybowls capable of columnar stacking. The synthesis and resolution of such PICs are achieved, assignment of absolute configuration is established by comparison of ECD and VCD spectra with theory, and material characterization is reported. Evidence for columnar stacking in solution and in the crystal is presented.

The chemistry of branched condensed phosphates.

Condensed phosphates may exist as linear, cyclic or branched structures. Due to their important role in nature, linear polyphosphates have been well studied. In contrast, branched phosphates (ultraphosphates) remain largely uncharacterised, because they were already described in 1950 as exceedingly unstable in the presence of water, epitomized in the antibranching-rule. This rule lacks experimental backup, since, to the best of our knowledge, no rational synthesis of defined ultraphosphates is known. Consequently, detailed studies of their chemical properties, reactivity and potential biological relevance remain elusive. Here, we introduce a general synthesis of monodisperse ultraphosphates. Hydrolysis half-lives up to days call the antibranching-rule into question. We provide evidence for the interaction of an enzyme with ultraphosphates and discover a rearrangement linearizing the branched structure. Moreover, ultraphosphate can phosphorylate nucleophiles such as amino acids and nucleosides with implications for prebiotic chemistry. Our results provide an entry point into the uncharted territory of branched condensed phosphates.

Spontaneous and induced chiral symmetry breaking of stereolabile pillar[5]arene derivatives upon crystallisation.

Stereolabile pillar[5]arene (P[5]) derivatives, which are dynamic racemic mixtures in solution on account of their low inversion barriers, were employed as platforms to study chiral symmetry breaking during crystallisation. In the solid state, we showed that crystal enantiomeric excess of a conglomerate-forming P[5] derivative can be obtained by handpicking and Viedma ripening without the intervention of external chiral entities. On the other hand, in the presence of ethyl d/l-lactate as both optically-active solvents and chiral guests, the handedness of P[5] derivative crystals, either forming racemic compounds or conglomerates upon condensation, can be directed and subsequently inverted in a highly controllable manner.

The Unusual Photochromic and Hydrochromic Switching Behavior of Cellulose-Embedded 1,8-Naphthalimide-Viologen Derivatives in the Solid-State.

Stimuli-responsive chromic materials such as photochromics, hydrochromics, thermochromics, and electrochromics have a long history of capturing the attention of scientists due to their potential industrial applications and novelty in popular culture. However, hybrid chromic materials that combine two or more stimuli-triggered color changing properties are not so well known. Herein, we report a design strategy that has led to a series of emissive 1,8-naphthalimide-viologen dyads which exhibit unusual dual photochromic and hydrochromic switching behavior in the solid-state when embedded in a cellulose matrix. This behavior manifests as reversible solid state fluorescence hydrochromism upon changes in atmospheric relative humidity (RH), and reversible solid state photochromism upon generation of a cellulose-stabilized viologen radical cation. In this design strategy, the bipyridinium unit serves as both a water-sensitive receptor for the hydrochromic fluorophore-receptor system, and a photochromic group, capable of eliciting its own visible colorimetric response, generating a fluorescence quenching radical cation with prolonged exposure to ultraviolet (UV) light. These dyes can be inkjet-printed onto cellulose paper or drop-cast as cellulose powder-based films and can be unidirectionally cycled between three different states which can be characteristically visualized under UV light or visible light. The material's photochromism, hydrochromism, and underlying mechanism of action was investigated using computational analysis, dynamic vapor sorption/desorption isotherms, electron paramagnetic resonance spectroscopy, and variable humidity UV-Vis adsorption and fluorescence spectroscopies.

Synthesis and Acidity of 5-(m-Terphenyl-2'-yl)-1H-tetrazoles: Evidence for an Enhanced Polar-π Effect Compared to Carboxylic Acids.

The polar-π effect on tetrazoles, medicinal chemistry isosteres of carboxylate, is tested by a Hammett pKa (microtitration) analysis over a series of 5-(m-terphenyl-2'-yl)-1H-tetrazoles. A comparison with m-terphenyl-2'-yl-carboxylic acids supports the isostere analogy also in response to environmental changes. Computational (B97D/def2TZVPPD) extension of the series plus a scan of solvents (vacuum to water) demonstrates the trend with the dielectric constant. The effect is energetically small but may make statistically significant contributions to the tetrazole pharmacological profile.

Transition-Metal Catalysis of Triene 6π Electrocyclization: The π-Complexation Strategy Realized.

Triene 6π electrocyclization, wherein a conjugated triene undergoes a concerted stereospecific cycloisomerization to a cyclohexadiene, is a reaction of great historical and practical significance. In order to circumvent limitations imposed by the normally harsh reaction conditions, chemists have long sought to develop catalytic variants based upon the activating power of metal-alkene coordination. Herein, we demonstrate the first successful implementation of such a strategy by utilizing [(C5 H5 )Ru(NCMe)3 ]PF6 as a precatalyst for the disrotatory 6π electrocyclization of highly substituted trienes that are resistant to thermal cyclization. Mechanistic and computational studies implicate hexahapto transition-metal coordination as responsible for lowering the energetic barrier to ring closure. This work establishes a foundation for the development of new catalysts for stereoselective electrocyclizations.

Generalized Analytic Approach for Determination of Multidimensional Franck-Condon Factors: Simulated Photoelectron Spectra of Polynuclear Aromatic Hydrocarbons.

An enhanced generalized analytic approach for determination of multidimensional Franck-Condon Factors (FCFs) enables efficient computational prediction of photoelectron spectra for large-dimensional systems. Incorporation of the automated assignment of Cartesian coordinate handedness and coordinate superposition between the ground and excited electronic states satisfies the Eckart conditions and allows evaluation of the Duschinsky effect. The model shows excellent agreement with experiments for the determination of FCFs and photoelectron spectra of a series of increasing dimensions polynuclear hydrocarbons (PAHs), including naphthalene, anthracene, phenanthrene, and pyrene. In addition, a high-resolution prediction of the PES for the 84-dimensional PAH corannulene provides motivation for an additional experimental study. For FCFs, coordinate transformation between the initial and final states rather than the dimension of the systems more greatly influences the complexity of the spectral band shapes.

Classical and non-classical melatonin receptor agonist-directed micellization of bipyridinium-based supramolecular amphiphiles in water.

The addition of molecular recognition units into structures of amphiphiles is a means by which soft matter capable of undergoing template-directed micellization can be obtained. These supramolecular amphiphiles can bind with molecular templates using non-covalent bonding interactions, forming host-guest complexes that hold the amphiphiles together as they undergo micellization. In most cases, such templates are synthesized and designed for a specific molecular recognition motif. It is not clear, however, to what extent these types of amphiphile systems are responsive to members of a biologically derived class of molecular targets, for example, melatonin receptor agonists and their numerous isosteres. Herein, we describe the template-directed micellization and arrangement at the air-water interface of a bipyridinium-based gemini surfactant, driven by the influence of donor-acceptor CT interactions with a series of bioactive classical and non-classical melatonin isosteres. Under the conditions of templation by either 5-methoxytryptophol, N-acetylserotonin, N-acetyltryptamine, or the pharmaceutical agent agomelatine, favorable Gibbs free energies of micellization were observed with decreases in CMC by up to 70%, and concomitant increases of 28% in surface pressure, and decreases of 20% in contact angle versus untemplated solutions. Solid state thermochromic transition temperatures for inkjet-printed patterns of the templated amphiphile solutions were inversely correlated with trends observed for their respective CMCs, and exhibited no correlation to their binding constants. These findings contend for the generalizable use of melatonin receptor agonists as targets and/or templates for chemical systems, which rely on π-stacking donor-acceptor CT interactions in water to facilitate the actions of binding, sequestration, or template-directed self-assembly.

X-ray Crystallography and Unexpected Chiroptical Properties Reassign the Configuration of Haliclonadiamine.

Haliclonadiamine and papuamine are bis-indane marine natural products isolated from the marine sponge Haliclona sp. Their relative structures were previously reported to differ by inversion at only one of their eight shared stereocenters. Here X-ray crystallography shows the opposite to be true: papuamine has a 1R,3S,8R,9S,14S,15R,20S,22R configuration, while haliclonadiamine has a 1S,3R,8S,9R,14R,15S,20R,22R configuration. Paradoxically the ECD of each structure displays a negative Cotton effect. X-ray crystallography reveals the two structures adopt similar conformations of their 13-membered macrocyclic core that comprises a configurationally relevant diene. B97x-D/Def2-TZVPP-(MeOH)-calculated ECD supports the diene configuration with the macrocycle dominating the ECD Cotton effect for haliclonadiamine and papuamine. Additional crystallographic and chiroptical analyses of three sponge samples from geographically distant locations indicate this pair of natural products always exists as a configurationally related couple. The co-discovery of a biosynthetic precursor, halichondriamine C, present in these same Haliclona samples must be considered when discussing any biosynthetic pathway. Taken together, this work justifies a reassignment of haliclonadiamine's structure and opens the question of how this complex stereochemical relationship between haliclonadiamine and palauamine arises biosynthetically.

Involvement of aryl hydrocarbon receptor in the cytotoxicity of corannulene and its derivatives.

Despite numerous studies on the toxicities of planar polycyclic aromatic hydrocarbons (PAHs), very little is known about the toxicological profiles of non-planar PAHs. In the present study, the cytotoxicity of corannulene (COR), a typical bowl-shaped PAH with a myriad of applications in the area of material chemistry, and benzo[a]pyrene (BaP), a typical planar PAH with similar molecular weight, were systematically compared in various cell lines. Compared with BaP, exposure to COR resulted in less cytotoxic responses in both human (HepG2) and murine (Hepa1-6) hepatoma cells, which was characterized with a slower cellular accumulation as well as a weaker induction of cytochrome P450 1 (CYP1/Cyp1) isozymes. Knockdown of aryl hydrocarbon receptor (AhR) by siRNA attenuated the inductive effect of COR on CYP1A/Cyp1a mRNA levels in these two cell lines. Further analysis revealed that derivatization greatly influenced the cytotoxicity of COR, which was positively correlated with their binding affinities to the AhR, as demonstrated by in silico molecular docking. Overall, these results suggest that AhR appears to be involved in the cytotoxic responses of COR and its derivatives, providing a fundamental understanding of the biological effects of bowl-like PAHs.

Fluorous Corannulenes: Ab initio Predictions and the Synthesis of sym-Pentafluorocorannulene.

Ten sym-penta and deca-X substituted corannulenes (1-10; X=H, F, CH3 , or CF3 ) define a library of fluorous compounds comprising high symmetry non-planar aromatic compunds. They provide a group of structurally similar, yet physically distinct structures manifesting special chemical behavior related to their degree of fluorination. Owing to their bowl forms, corannulene derivatives are distinct from planar polynuclear aromatic compounds; they have relatively high dipole moments, accept 1-4 electrons, and display room temperature fluorescence as well as low temp phosphorescence. Electronic structure theory predicts the bowl inversion barrier and physical properties. The syntheses of sym-pentafluorocorannulene by an efficient late stage fluorination affords a key derivative to calibrate predictions.

Acid-Induced Liberation of Polysubstituted Cyclopentadiene Ligands from Cyclopentadienyl Cobalt: A [2 + 2 + 1] Cycloaddition Route toward 1,2,4-Trisubstituted Cyclopentadienes.

Here, we report that trifluoroacetic acid (TFAH) induces demetallation and protodesilylation of the cyclopentadiene ligand in cobalt-η4-cyclopentadiene complexes of general formula [(η5-C5H5)Co(η4-exo-C(TMS)═C(SO2Ph)CH═CRCH(CO2Et))] (1-Ph, R = Ph; 1-ArtBu, R = p-C6H4tBu; 1-ArNMe2, R = p-C6H4NMe2; and 1-Me, R = Me). The trisubstituted cyclopentadiene products are isolated as a mixture of two tautomers, [(CH2C(SO2Ph)═CHC(CO2Et)═CR)] (8-R-A) and [(CH═C(SO2Ph)CH2C(CO2Et)═CR)] (8-R-B). The endo isomer, [(η5-C5H5)Co(η4-endo-C(TMS)═C(SO2Ph)CH═CPhCH(CO2Et))] (1-Ph-endo), also undergoes demetallation and protodesilylation to give 8-Ph-A and 8-Ph-B in excellent yield. The cobalt-cyclopentadiene complex, [(η5-C5H5)Co(η4-exo-C(TMS)═C(SO2Ph)CH═C(CO2Me)CH(CO2Et))] (1-CO2Me), undergoes demetallation and protodesilylation upon treatment with TFAH to give a hydrogen-bonded fulvenol (8-CO2Me). Liberation of the ethoxy-substituted cyclopentadiene ligand of [(η5-C5H5)Co(η4-exo-C(TMS)═C(SO2Ph)CH═C(OEt)CH(CO2Et))] (1-OEt) leads to formation of a cyclopentenone derivative (11). Thermolysis of 8-Ph-A/8-Ph-B in the presence of maleimide leads to a highly functionalized Diels-Alder adduct, whereas 8-Ph-A/8-Ph-B serves as precursors to trisubstituted ruthenocenes by in situ deprotonation and reaction with [(η5-C5R5)Ru(NCMe)3]PF6 (16-H, R = H; 16-Me, R = Me).

Synthesis of Modified Nucleoside Oligophosphates Simplified: Fast, Pure, and Protecting Group Free.

Phosphoramidite analogues of modified cyclotriphosphates provide a general and step-economical synthesis of nucleoside triphosphates and analogues on scale without the need for protecting groups. These reagents enable rapid access to pure nucleoside oligophosphates and a range of other analogues that were previously difficult to obtain (e.g., NH, CH2, CCl2, and CF2 replacements for O, phosphono- and phosphoimidazolides, -morpholidates, -azidates, and -fluoridates). DFT calculations demonstrate that the selectivity of the cyclotriphosphate opening reactions proceeds via an in-line substitution mechanism that displaces the least charged leaving group.

Diastereoselective Monofluorocyclopropanation Using Fluoromethylsulfonium Salts.

Diarylfluoromethylsulfonium salts, alternatives to freons or advanced fluorinated building blocks, are bench stable and easy-to-use sources of direct fluoromethylene (:CHF) transfer to alkenes. These salts enabled development of a trans-selective monofluorinated Johnson-Corey-Chaykovsky reaction with vinyl sulfones or vinyl sulfonamides to access synthetically challenging monofluorocyclopropane scaffolds. The described method offers rapid access to monofluorinated cyclopropane building blocks with further functionalization opportunities to deliver more complex synthetic targets diastereoselectively.

Pathways towards true catalysts: computational modelling and structural transformations of Zn-polyoxotungstates.

Current catalysis undergoes a paradigm shift from molecular and heterogeneous realms towards new dynamic catalyst concepts. This calls for innovative strategies to understand the essential catalytic motifs and true catalysts emerging from oxidative transformation processes. Polyoxometalate (POM) clusters offer an inexhaustible reservoir for new noble metal-free catalysts and excellent model systems whose structure-activity relationships and mechanisms remain to be explored. Here, we first introduce a new {ZnnNa6-n(B-α-SbW9O33)2} (n = 3-6) catalyst family with remarkable tuning options of the Zn-based core structure and high activity in H2O2-assisted catalytic alcohol oxidation as a representative reaction. Next, high level solution-based computational modelling of the intermediates and transition states was carried out for [Zn6Cl6(SbW9O33)2]12- as a representative well-defined case. The results indicate a radical-based oxidation process with the involvement of tungsten and adjacent zinc metal centers. The {ZnnNa6-n(B-α-SbW9O33)2} series indeed efficiently catalyses alcohol oxidation via peroxotungstate intermediates, in agreement with strong spectroscopic support and other experimental evidence for the radical mechanism. Finally, the high performance of [Zn6Cl6(SbW9O33)2]12- was traced back to its transformation into a highly active and robust disordered Zn/W-POM catalyst. The atomic short-range structure of this resting pre-catalyst was elucidated by RMC modelling of the experimental W-L3 and Zn-K edge EXAFS spectra and supported with further analytical methods. We demonstrate that computational identification of the reactive sites combined with the analytical tracking of their dynamic transformations provides essential input to expedite cluster-based molecular catalyst design.