Electron Storage System Based on a Two-Way Inversion of Redox Potentials.

Molecular-level multielectron handling toward electrical storage is a worthwhile approach to solar energy harvesting. Here, a strategy which uses chemical bonds as electron reservoirs is introduced to demonstrate the new concept of "structronics" (a neologism derived from "structure" and "electronics"). Through this concept, we establish, synthesize, and thoroughly study two multicomponent "super-electrophores": 1,8-dipyridyliumnaphthalene, 2, and its N,N-bridged cyclophane-like analogue, 3. Within both of them, a covalent bond can be formed and subsequently broken electrochemically. These superelectrophores are based on two electrophoric (pyridinium) units that are, on purpose, spatially arranged by a naphthalene scaffold. A key characteristic of 2 and 3 is that they possess a LUMO that develops through space as the result of the interaction between the closely positioned electrophoric units. In the context of electron storage, this "super-LUMO" serves as an empty reservoir, which can be filled by a two-electron reduction, giving rise to an elongated C-C bond or "super-HOMO". Because of its weakened nature, this bond can undergo an electrochemically driven cleavage at a significantly more anodic-yet accessible-potential, thereby restoring the availability of the electron pair (reservoir emptying). In the representative case study of 2, an inversion of potential in both of the two-electron processes of bond formation and bond-cleavage is demonstrated. Overall, the structronic function is characterized by an electrochemical hysteresis and a chemical reversibility. This structronic superelectrophore can be viewed as the three-dimensional counterpart of benchmark methyl viologen (MV).

Kinetics of Multielectron Transfers and Redox-Induced Structural Changes in N-Aryl-Expanded Pyridiniums: Establishing Their Unusual, Versatile Electrophoric Activity.

A combined electrochemical and theoretical study of a series of pyridinium-based electrophores, consisting of reference N-alkyl-2,4,6-triarylpyridiniums (1-3) and N-aryl-expanded pyridiniums (EPs), i.e. N-aryl-2,4,6-triarylpyridiniums (4-10), is presented with the aim of elucidating multifaceted mechanisms underpinning the complex electrophoric activity of fluxional EP systems. Series 1-10 constitutes a library of model electrophores showing an incremental variation of their composition, charge, and steric hindrance. By kinetic mapping of the first two heterogeneous electron transfers (ETs) of 1-10 and computational mapping, at the density functional theory level, of their electronic and geometrical features in various redox states, it is established that, depending on whether EPs are made of one (4, 5) or two "head-to-tail"-connected pyridinium rings (6-10), the nature of the redox-triggered distortions (when allowed) is different, namely, N-pyramidalization due to hybridization change in the former case versus saddle-shaped distortion originating from conflicting intramolecular interactions in the latter case (8-10). When skeletal relaxations are sterically hampered, zwitterionic states and electron delocalization with quinoidal features are promoted as alternative relaxation modes. It follows that "potential compression" is changed to "potential expansion" (i.e., a further separation of redox potentials) in single-pyridinium EPs (4, 5), whereas "potential inversion" (i.e., single-step two-electron transfer; 8-10) is changed to stepwise ETs of the Weitz type for two-pyridinium EPs (6, 7). Overall, kinetic rate constants not only consistently indicate the most prominent mechanistic aspects of the reduction pathways of EPs, but they are also instrumental in establishing EPs as a unique class of electrophores.

Nonclassical CH-π supramolecular interactions in artemisinic acid favor a single conformation, yielding high diastereoselectivity in the reduction with diazene.

The high diastereoselectivity of the hydrogenation of artemisinate by diazene to form dihydroartemisinate (diastereoselective ratio, dr, 97:3) necessary for efficient production of artemisin has been rationalized by state-of-the-art DFT calculations and identification of the noncovalent interactions by coupled ELF/NCI analysis. Remarkably, a single conformer of artemisinate is responsible for the high diastereoselectivity of the reaction. NMR studies confirm the preference for a single conformation that is found to be identical to that predicted by the calculations. The calculations and ELF/NCI analyses show that the hydrogenation of the exocyclic activated C═C double bond has a low energy barrier and that the lowest transition state and the preferred conformation of free artemisinate develop the same network of weak noncovalent interactions between the electron donor groups (oxygen and exocyclic C═C double bond) and CH bonds of the cis-decalene group of the artemisinate, which rationalize the high diastereoselectivity unusual for a strongly exothermic reaction.

Diastereomeric spirooxindoles as highly potent and efficacious MDM2 inhibitors.

Small-molecule inhibitors that block the MDM2-p53 protein-protein interaction (MDM2 inhibitors) are being intensely pursued as a new therapeutic strategy for cancer treatment. We previously published a series of spirooxindole-containing compounds as a new class of MDM2 small-molecule inhibitors. We report herein a reversible ring-opening-cyclization reaction for some of these spirooxindoles, which affords four diastereomers from a single compound. Our biochemical binding data showed that the stereochemistry in this class of compounds has a major effect on their binding affinities to MDM2, with >100-fold difference between the most potent and the least potent stereoisomers. Our study has led to the identification of a set of highly potent MDM2 inhibitors with a stereochemistry that is different from that of our previously reported compounds. The most potent compound (MI-888) binds to MDM2 with a Ki value of 0.44 nM and achieves complete and long-lasting tumor regression in an animal model of human cancer.

Molecular dyads of ruthenium(II)- or osmium(II)-bis(terpyridine) chromophores and expanded pyridinium acceptors: equilibration between MLCT and charge-separated excited states.

The synthesis, characterization, redox behavior, and photophysical properties (both at room temperature in fluid solution and at 77 K in rigid matrix) of a series of four new molecular dyads (2-5) containing Ru(II)- or Os(II)-bis(terpyridine) subunits as chromophores and various expanded pyridinium subunits as electron acceptors are reported, along with the reference properties of a formerly reported dyad, 1. The molecular dyads 2-4 have been designed to have their (potentially emissive) triplet metal-to-ligand charge-transfer (MLCT) and charge-separated (CS) states close in energy, so that excited-state equilibration between these levels can take place. Such a situation is not shared by limit cases 1 and 5. For dyad 1, forward photoinduced electron transfer (time constant, 7 ps) and subsequent charge recombination (time constant, 45 ps) are evidenced, while for dyad 5, photoinduced electron transfer is thermodynamically forbidden so that MLCT decays are the only active deactivation processes. As regards 2-4, CS states are formed from MLCT states with time constants of a few dozens of picoseconds. However, for these latter species, such experimental time constants are not due to photoinduced charge separation but are related to the excited-state equilibration times. Comparative analysis of time constants for charge recombination from the CS states based on proper thermodynamic and kinetic models highlighted that, in spite of their apparently affiliated structures, dyads 1-4 do not constitute a homologous series of compounds as far as intercomponent electron transfer processes are concerned.

Tictoid expanded pyridiniums: assessing structural, electrochemical, electronic, and photophysical features.

In regard to semirigid donor-spacer-acceptor (D-S-A) dyads devised for photoinduced charge separation and built from an unsaturated spacer, there exists a strategy of design referred to as "geometrical decoupling" that consists in introducing an inner-S twist angle approaching 90° to minimize adverse D/A mutual electronic influence. The present work aims at gaining further insights into the actual impact of the use of bulky substituents (R) of the alkyl type on the electronic structure of spacers (S) of the oligo-p-phenylene type, which can be critical in the functioning of derived dyads. To this end, a series of 12 novel expanded pyridiniums (EPs), regarded as model S-A assemblies, was synthesized and its structural, electronic, and photophysical properties were investigated at both experimental and theoretical levels. These EPs result from the combination of 4 types of pyridinium-based acceptor moieties with the three following types of S subunits connected at position 4 of the pyridinum core: xylyl (X), xylyl-phenyl (XP), and xylyl-tolyl (XT). From comparison of collected data with those already reported for eight other EPs based on the same A components but linked to S fragments of two other types (i.e., phenyl, P, and biphenyl, PP), the following quantitative order in regard to the pivotal S-centered HOMO energy perturbation was derived (sorted by increasing destabilization): P < X ≪ PP ≈< XP ≈< XT. This indicates that spacers (S) are primarily distinguished on the basis of their mono- or biaryl composition and secondarily by their number of methyl substituents (R). The electron-donating inductive contribution of methyl substituents (HOMO destabilization) more than counterbalances the effect of conjugation disruption (HOMO stabilization). This "compensation effect" suggests that mildly electron-withdrawing hindering groups are better suited for "geometrical decoupling", given that high-energy S-centered occupied MOs can assist charge recombination within D-S-A dyads.

Expanded pyridiniums: bis-cyclization of branched pyridiniums into their fused polycyclic and positively charged derivatives--assessing the impact of pericondensation on structural, electrochemical, electronic, and photophysical features.

This study evaluates the impact of the extension of the π-conjugated system of pyridiniums on their various properties. The molecular scaffold of aryl-substituted expanded pyridiniums (referred to as branched species) can be photochemically bis-cyclized into the corresponding fused polycyclic derivatives (referred to as pericondensed species). The representative 1,2,4,6-tetraphenylpyridinium (1(H)) and 1,2,3,5,6-pentaphenyl-4-(p-tolyl)pyridinium (2(Me)) tetra- and hexa-branched pyridiniums are herein compared with their corresponding pericondensed derivatives, the fully fused 9-phenylbenzo[1,2]quinolizino[3,4,5,6-def]phenanthridinium (1(H)f) and the hitherto unknown hemifused 9-methyl-1,2,3-triphenylbenzo[h]phenanthro[9,10,1-def]isoquinolinium (2(Me)f). Combined solid-state X-ray crystallography and solution NMR experiments showed that stacking interactions are barely efficient when the pericondensed pyridiniums are not appropriately substituted. The electrochemical study revealed that the first reduction process of all the expanded pyridiniums occurs at around -1 V vs. SCE, which indicates that the lowest unoccupied molecular orbital (LUMO) remains essentially localized on the pyridinium core regardless of pericondensation. In contrast, the electronic and photophysical properties are significantly affected on going from branched to pericondensed pyridiniums. Typically, the number of absorption bands increases with extended activity towards the visible region (down to ca. 450 nm in MeCN), whereas emission quantum yields are increased by three orders of magnitude (at ca. 0.25 on average). A relationship is established between the observed differential impact of the pericondensation and the importance of the localized LUMO on the properties considered: predominant for the first reduction process compared with secondary for the optical and photophysical properties.

Photochemically driven intercalation of small molecules into DNA by in situ irradiation.

Intercalation of small molecules into DNA is photochemically achieved by in situ irradiation of a tetraaryl-pyridinium species. Such a "DNA intercalation on demand" process could highlight an alternative pathway to anticancer basic research, based on photo-activable DNA binders.

Photoinduced processes within compact dyads based on triphenylpyridinium-functionalized bipyridyl complexes of ruthenium(II).

As an alternative to conventional charge-separation functional molecular models based on long-range ET within redox cascades, a "compact approach" has been examined. To this end, spacer elements usually inserted between main redox-active units within polyad systems have been removed, allowing extended rigidity but at the expense of enhanced intercomponent electronic communication. The molecular assemblies investigated here are of the P-(theta (1))-A type, where the theta (1) twist angle is related to the degree of conjugation between the photosensitizer (P, of {Ru(bpy)(3)}(2+) type) and the electron-acceptor (A). 4-N- and 4-N-,4'-N-(2,4,6-triphenylpyridinio)-2,2'-bipyridine ligands (A(1)-bpy and A(2)-bpy, respectively) have been synthesized to give complexes with Ru(II), 1-bpy and 2-bpy, respectively. Combined solid-state analysis (X-ray crystallography), solution studies ((1)H NMR, cyclic voltammetry) and computational structural optimization allowed verifying that theta (1) angle approaches 90 degrees within 1-bpy and 2-bpy in solution. Also, anticipated existence of strong intercomponent electronic coupling has been confirmed by investigating electronic absorption properties and electrochemical behavior of the compounds. The capability of 1-bpy and 2-bpy to undergo PET process was evaluated by carrying out their photophysical study (steady state emission and time-resolved spectroscopy at both 293 and 77 K). The conformational dependence of photoinduced processes within P-(theta (1))-A systems has been established by comparing the photophysical properties of 1-bpy (and 2-bpy) with those of an affiliated species reported in the literature, 1-phen. A complementary theoretical analysis (DFT) of the change of spin density distribution within model [1-bpy(theta (1))](-) mono-reduced species as a function of theta (1) has been undertaken and the possibility of conformationally switching emission properties of P was derived.

A new class of functionalized terpyridyl ligands as building blocks for photosensitized supramolecular architectures. Synthesis, structural, and electronic characterizations.

A new class of triarylpyridinio-derivatized [4'-(p-phenyl)(n)]terpyridyl ligands, R(1)(2)R(2)TP(+)-(p)(n)tpy, was designed as a novel category of electron-acceptor (A)-substituted proto-photosensitizing molecules. The first elements of this versatile family of ligands (i.e., n = 0, 1 and R(1) = R(2) = H), H(3)TP(+)-tpy and H(3)TP(+)-ptpy, were synthesized as well as their Ru(II) and Os(II) complexes to form the related acceptor-functionalized M(tpy)(2)(2+) and M(ptpy)(2)(2+) photosensitizer components denoted P0 and P1, respectively. Within the P1 series of compounds, an electron-donor (D)-substituted ligand, Me(2)N-ptpy, was also involved and associated with H(3)TP(+)-ptpy, giving rise to various combinations (up to 10 polyad systems). The two resulting series of nanometer-scale rigid rod-like photosensitized supramolecular architectures are of potential interest for long-range photoinduced electron transfer purposes. The main structural features of such supermolecules were determined by comparing the results obtained from (i) single-crystal X-ray analysis of the two free ligands together with that of the P0A/Ru and P1A(2)/Ru complexes and (ii) a detailed solution (1)H NMR study of the P0 series and, more specifically, of the P0A/Ru dyad (ROESY experiment). It is shown that the pseudoperpendicular conformation of the covalently linked A and P subunits found in the solid state is persistent in fluid medium; i.e., A is not conjugated with P (P0 and P1). The first insights regarding the consequences upon intercomponent couplings of combined substituent effects and conjugation (case of D-based polyads)-or absence of conjugation-are discussed in the light of ground-state electronic properties of the compounds.

Induced fit process in the selective distal binding of imidazoles in zinc(II) porphyrin receptors.

The respective affinities of various imidazole derivatives, imidazole (ImH), 2-methylimidazole (2-MeImH), 2-phenylimidazole (2-PhImH), N-methylimidazole (N-MeIm), 2-methylbenzimidazole (2-MeBzImH), and 4,5-dimethylbenzimidazole (4,5-Me(2)BzImH), for two phenanthroline (Phen) strapped zinc(II) porphyrin receptors porphen-Zn 1-Zn and 2-Zn have been studied. The formation of a supplementary H-bond considerably enhances the affinity of the zinc(II)-porphen receptor for imidazoles unsubstituted on the pyrrolic nitrogen (ImH) versus N-substituted imidazoles such as N-MeIm. The ImHs subset porphen-Zn complexes are formed with association constants up to 4 orders of magnitude superior to those measured either for N-MeIm as substrate or TPP-Zn as receptor. Distal or proximal binding of the substrates was determined by (1)H NMR measurements and titration. In two cases, the very high stability of the inclusion complex enabled the use of 2D NMR techniques. Excellent correlation between solution and solid-state structures has been obtained. A total of six X-ray structures are detailed in this article showing that the evolution of the shape of the zinc(II) receptor is mostly dependent on the steric constraints induced by the substitution on the imidazole. Hindered guests also progressively induce considerable mobility restrictions and severe distortions on the receptor, especially in the case of 2-MeBzImH and 2-PhImH.