From Stilbenes to carbo-Stilbenes: an Encouraging Prospect.

Beyond previously described carbo-naphthalene and carbo-biphenyl, a novel type of bis-carbo-benzenic molecules is envisaged from the stilbene parent. The synthesis, structure, spectroscopic and electrochemical properties of two such carbo-stilbenes are described at complementary experimental and computational DFT levels. In the selected targets, the bare skeletal carbo-mer of carbo-stilbene is decorated by 8 or 10 phenyl groups, 0 or 2 tert-butyl groups, and 2 n-octyl chains, the later substituents being introduced to compensate anticipated solubility issues. As in the parent stilbene series, isomers of the phenylated carbo-stilbenes are characterized. The cis- and trans-isomers are, however, formed in almost equal amounts and could not be separated by either chromatography or crystallization. Nevertheless, due to a slow interconversion at the NMR time scale (up to 55 °C) the 1H NMR signals of both isomers of the two carbo-stilbenes could be tentatively assigned. The calculated structure of the cis-isomer exhibits a helical shape, consistent with the observed magnetic shielding of phenyl p-CH nuclei residing inside the shielding cone of the facing C18 ring. The presence of the two isomers in solution also gives rise to quite broad UV-vis absorption spectra with main bands at ca 460, 560 and 710 nm, and a significant bathochromic shift for the decaphenylated carbo-stilbene vs the di-tert-butyl-octaphenylated counterpart. Square wave voltammograms do not show any resolution of the two isomers, giving a reversible reduction wave at -0.65 or -0.58 V/SCE, and an irreversible oxidation peak at 1.11 V/SCE, those values being classical for most carbo-benzene derivatives. Calculated NICS values (NICS(1)=-12.5±0.2 ppm) also indicate that the aromatic nature of the C18 rings is not markedly affected by the dialkynylbutatriene (DAB) connector between them.

Carbo-mer of Barrelene: A Rigid 3D-Carbon-Expanded Molecular Barrel.

After extensive studies of 1D and 2D skeletal carbo-mers based on C8 π-conjugating dialkynylbutatriene units (DABs: ∼C≡C-(R)C=C=C=C(R)-C≡C∼) bridging sp or sp2 centers in carbo-butene, carbo-xylylene or carbo-benzene derivatives, 3D versions are envisaged through carbo-barrelenes and partially reduced derivatives thereof where two or three DAB blades span a bridge between sp3 carbinol vertices or ether thereof. For R=Ph, stable representatives were synthesized through a pivotal [6]pericyclynedione, and extensively characterized by spectroscopic, electrochemical and crystallographic methods. Density functional theory calculations allow detailed analysis of structural and electronic features of the 7 Šhigh C26 barrel-shaped molecules, and show that they can behave as cages for ionic species. Beyond aesthetical concerns, the results could open prospects of applications in host-guest supramolecular chemistry and single molecule charge transport.

Further Insights into the Oxidative Pathway of Thiocarbonyl-Type Antitubercular Prodrugs: Ethionamide, Thioacetazone, and Isoxyl.

A chemical activation study of the thiocarbonyl-type antitubercular prodrugs, ethionamide (ETH), thioacetazone (TAZ), and isoxyl (ISO), was performed. Biomimetic oxidation of ethionamide using H2O2 (1 equiv) led to ETH-SO as the only stable S-oxide compound, which was found to occur in solution in the preferential form of a sulfine (ETH═S═O vs the sulfenic acid tautomer ETH-S-OH), as previously observed in the crystal state. It was also demonstrated that ETH-SO is capable of reacting with amines, as the putative sulfinic derivative (ETH-SO2H) was supposed to do. Unlike ETH, oxidation of TAZ did not allow observation of the mono-oxygenated species (TAZ-SO), leading directly to the more stable sulfinic acid derivative (TAZ-SO2H), which can then lose a SOxH group after further oxidation or when placed in a basic medium. It was also noticed that the unstable TAZ-SO intermediate can lead to the carbodiimide derivative as another electrophilic species. It is suggested that TAZ-SOH, TAZ-SO2H, and the carbodiimide compound can also react with NH2-containing nucleophilic species, and therefore be involved in toxic effects. Finally, ISO showed a very complex reactivity, here assigned to the coexistence of two mono-oxygenated structures, the sulfine and sulfenic acid tautomers. The mono- and dioxygenated derivatives of ISO are also highly unstable, leading to a panel of multiple metabolites, which are still reactive and likely contribute to the toxicity of this prodrug.

Pentacyanoferrate(II) complex of pyridine-4- and pyrazine-2-hydroxamic acid as source of HNO: investigation of anti-tubercular and vasodilation activities.

A pharmacophore design approach, based on the coordination chemistry of an intimate molecular hybrid of active metabolites of pro-drugs, known to release active species upon enzymatic oxidative activation, is devised. This is exemplified by combining two anti-mycobacterial drugs: pyrazinamide (first line) and delamanid (third line) whose active metabolites are pyrazinoic acid (PyzCOOH) and likely nitroxyl (HNO (or NO.)), respectively. Aiming to generate those active species, a hybrid compound was envisaged by coordination of pyrazine-2-hydroxamic acid (PyzCONHOH) with a Na3[FeII(CN)5] moiety. The corresponding pentacyanoferrate(II) complex Na4[FeII(CN)5(PyzCONHO-)] was synthesized and characterized by several spectroscopic techniques, cyclic voltammetry, and DFT calculations. Chemical oxidation of this complex with H2O2 was shown to induce the release of the metabolite PyzCOOH, without the need of the Mycobacterium tuberculosis (Mtb) pyrazinamidase enzyme (PncA). Control experiments show that both H2O2- and N-coordinated pyrazine FeII species are required, ruling out a direct hydrolysis of the hydroxamic acid or an alternative oxidative route through chelation of a metal center by a hydroxamic group. The release of HNO was observed using EPR spectroscopy in the presence of a spin trapping agent. The devised iron metal complex of pyrazine-2-hydroxamic acid was found inactive against an actively growing/non-resistant Mtb strain; however, it showed a strong dose-dependent and reversible vasodilatory activity with mostly lesser toxic effects than the reference drug sodium nitroprussiate, unveiling thus a potential indication for acute or chronic cardiovascular pathology. This is a priori a further indirect evidence of HNO release from this metal complex, standing as a possible pharmacophore model for an alternative vasodilator drug.

Core carbo-mer of an Extended Tetrathiafulvalene: Redox-Controlled Reversible Conversion to a carbo-Benzenic Dication.

carbo-Benzene is an aromatic molecule devised by inserting C2 units within each C-C bond of the benzene molecule. By integrating the corresponding carbo-quinoid core as bridging unit in a π-extended tetrathiafulvalene (exTTF), it is shown that a carbo-benzene ring can be reversibly formed by electrochemical reduction or oxidation. The so-called carbo-exTTF molecule was thus experimentally prepared and studied by UV-visible absorption spectroscopy and cyclic voltammetry, as well as by X-ray crystallography and by scanning tunneling microscopy (STM) on a surface of highly oriented pyrolytic graphite (HOPG). The molecule and its oxidized and reduced forms were subjected to a computational study at the density functional theory (DFT) level, supporting carbo-aromaticity as a driving force for the formation of the dication, radical cation, and radical anion. By allowing co-planarity of the dithiolylidene rings and carbo-quinoidal core, carbo-exTTFs present a promising new class of redox-active systems.

Cyclopropenylidenephosphoranes: Rearrangement to Azetidinylidene-Methylphosphoniums.

Attempts at preparing cyclopropenylphosphonium salts by P-quaternization of α-aminophosphines with bisdiisopropylaminocyclopropenium tetrafluoroborate led to azetidin-2-ylidene methylphosphoniums as unexpected isomers, in 57-85% yields. The basic structure of the products is discussed on the basis of X-ray crystallography analysis. The unprecedented 3 → 4 ring expansion process is argued to be driven by an ambivalent aromatic vs antiaromatic character (or loss of aromaticity) of the primary phosphonium product. On the basis of DFT calculations, a mechanism involving a concerted 1,4-hydride shift/electrocyclization process as the rate-determining step is proposed and discussed vs possible alternatives.

Steric/π-Electronic Insulation of the carbo-Benzene Ring: Dramatic Effects of tert-Butyl versus Phenyl Crowns on Geometric, Chromophoric, Redox, and Magnetic Properties.

Hexa-tert-butyl-carbo-benzene (C18 tBu6 ) and three phenylated counterparts (C18 tBum Ph6-m ; m=4, 2) have been synthesized. The peralkylated version (m=6) provides experimental access to intrinsic features of the insulated C18 core independently from the influence of π-conjugated substituent. Over the series, structural, spectroscopic, and electrochemical properties are compared with those of the hexaphenylated reference (m=0). Anchoring tBu substituents at the C18 macrocycle is shown to enhance stability and solubility, and to dramatically modify UV/Vis absorption and redox properties. Whereas all carbo-benzenes reported previously were obtained as dark-reddish/greenish solids, crystals and solutions of C18 tBu6 happen to be yellow (λmax =379 vs. 472 nm for C18 Ph6 ). In comparison to C18 Ph6 , the reduction of C18 tBu6 remains reversible, but occurs at twice as high an absolute potential (E1/2 =-1.36 vs. -0.72 V). Systematic XRD analyses and DFT calculations show that the C18 ring symmetry is the nearest to D6h for m=6, which indicates a maximum geometric aromaticity. According to calculated nucleus-independent chemical shifts (NICS), the macrocyclic magnetic aromaticity is also maximum for C18 tBu6 : NICS(0)=-17.2 ppm versus (-18.0±0.1) ppm for the theoretical references C18 H6 and C18 F6 , and -13.5 ppm for C18 Ph6 . Accurate correlations of NICS(0) with experimentally recorded or calculated maximum UV/Vis absorption wavelengths, λmax , and chemical hardness, η=ELUMO -EHOMO , are evidenced.

Carbo-biphenyls and Carbo-terphenyls: Oligo(phenylene ethynylene) Ring Carbo-mers.

Ring carbo-mers of oligo(phenylene ethynylene)s (OPEn, n=0-2), made of C2 -catenated C18 carbo-benzene rings, have been synthesized and characterized by NMR and UV-vis spectroscopy, crystallography and voltammetry. Analyses of crystal and DFT-optimized structures show that the C18 rings preserve their individual aromatic character according to structural and magnetic criteria (NICS indices). Carbo-terphenyls (n=2) are reversibly reduced at ca. -0.42 V/SCE, i.e. 0.41 V more readily than the corresponding carbo-benzene (-0.83 V/SCE), thus revealing efficient inter-ring π-conjugation. An accurate linear fit of E1/2red1 vs. the DFT LUMO energy suggests a notably higher value (-0.30 V/SCE) for a carbo-quaterphenyl congener (n=3). Increase with n of the effective π-conjugation is also evidenced by a red shift of two of the three main visible light absorption bands, all being assigned to TDDFT-calculated excited states, one of them restricting to a HOMO→LUMO main one-electron transition.

Supramolecular Architecture of Substituted Tetraphenyl-carbo-benzenes from the Energetic Viewpoint.

The use of DFT-calculated energy-vector diagrams (EVDs) featuring the topology of pairwise intermolecular interaction energies is applied to crystals of carbo-benzenes. A homogeneous set of six ideally centrosymmetric tetraphenyl-carbo-benzenes is selected, with various substituents R in para positions: R=4-anisyl, 1-ethyl-2-phenyl-1H-indol-3-yl, 2-chloro-2-(1-ethyl-2-phenyl-1H-indol-3-yl)ethenyl, tetradecyl, and 9,9-dihexyl-9H-fluoren-2-yl, 2-(9,9-dihexyl-9H-fluoren-2-yl)ethynyl. The basic structural motifs (BSMs) of the crystals vary from layers to columns, depending on the size and shape of the substituents R. The BSM cohesion is shown to rely on π-stacking, CH-π and dispersive interactions. Solvate molecules are shown to have a negligible role in the formation of the BSM, whereas they loosen the interaction between neighbouring BSMs.

Lipidic Carbo-benzenes: Molecular Probes of Magnetic Anisotropy and Stacking Properties of α-Graphyne.

Solubilization of the C18 fundamental circuit of α-graphyne has been envisaged by decoration with aliphatic chains R = n-CnH2n+1. The synthesis and characterization of p-dialkyl-tetraphenyl-carbo-benzenes (n = 2, 8, 14, 20) are thus presented and compared to the monoalkyl series produced concomitantly. In both series, a dramatic enhancement of solubility in organic solvents (CH2Cl2, CHCl3) is observed for n ≥ 8, and in the dialkyl series, the melting-decomposition temperature of the solid products is shown to decrease linearly from 208 °C for n = 2 to 149 °C for n = 20. Fluoroalkyl analogues with R = n-C8H4F13 are also described. The products display classical UV-vis electronic spectra of carbo-benzenes in solution (λmax = 445.5 ± 1 nm, ε ≈ 200 000 L·mol-1·cm-1). They are also characterized by UV-vis absorption in the solid state, which is found to be correlated with the color and crystal packing. The methylene groups of R provide an experimental probe of the magnetic anisotropy and aromaticity of the C18 ring through the progressive NMR shielding of the 1H nuclei from ca. 4.70 to 1.25 ppm going away from the border of the ring (as far as 8 Å away). All alkyl-carbo-benzenes were also found to be highly crystalline. Seven of them have been characterized by X-ray diffraction analysis and the C18 columnar packing compared in a systematic manner. Crystals of the diethyl and bistetradecyl derivatives, containing no solvent molecule, provided the first examples of direct π-stacking of carbo-benzene rings, with inter-ring distances very close to calculated interlayer distances in AB and ABC α-graphityne (3.255 and 3.206 Å vs 3.266 and 3.201 Å, respectively).

Rh-Catalyzed Regioselective ortho-C-H Carbenoid Insertion of Diarylazines.

The Rh-catalyzed ortho-C-H carbenoid insertion reaction of diarylazines with diazo compounds has been developed. A wide range of ortho-substituted diarylazines have been obtained in moderate to high yields with high regioselectivity at room temperature. The hydrolysis of the products could release ketones or aldehydes, giving access to aromatic 1,5-keto-diesters as valuable synthons for further chemical transformations.

Towards Magnetic Carbo-meric Molecular Materials.

Numerous studies have underlined the putative diradical character of π-conjugated molecules that can be described by closed-shell Lewis structures, for instance, p-dimethylene p-n phenylenes, or long polyacenes. In the latter compounds, the only way to save the aromaticity of the six-membered rings is to give up the Lewis electron pairing in the singlet biradical ground state. The present work considers the possibility of doing the same by using the basic C2 units of carbo-meric architectures. A series of acyclic and cyclic carbo-meric architectures is studied by using UB3LYP DFT broken-symmetry calculations, including spin decontaminations and subsequent geometry optimization of the singlet diradical. The C2 units are shown to stabilize the singlet biradical by spin delocalization, two of them playing approximately the same role as one radical-insulating 1,4 phenylene moiety. The results are generalized to the investigation of open-shell polyradical singlet states of rigid hydrocarbon structures, the symmetry and rigidity of which can assist cooperativity and self spin polarization effect. Several synthesis targets with challenging magnetic/spin properties are suggested in the carbo-mer series.

Phosphenium Versus Pro-Phosphide Character of P-tert-butyl-dicyclopropeniophosphine: Zwitterionic Palladate Complexes of a Dicationic Phosphido Ligand.

With the view to enhancing the unique coordinating ability of the known phenyl-tetrakis(diisopropylamino)dicyclopropeniophosphine (Ph-DCP), replacement of the phenyl substituent by a tert-butyl substituent was envisaged. Both α-dicationic R-DCP phosphines, with R = Ph and tBu, were prepared in 54%-55% yield by substitution of RPCl2 with two equivalents of bis(diisopropylamino)-dicyclopropenylidene (BAC) and metathesis with NaBF4. This method is implicitly consistent with the representation of R-DCPs as BAC-phosphenium adducts. The R-DCP salts were found to coordinate hard and soft Lewis acids such as a promoted oxygen atom (in the singlet spin state) in the corresponding R-DCP oxides, and electron-rich transition-metal centers in η1-R-DCP complexes with AuCl, PtCl3-, or PdCl3-, respectively. Coordination of Ph-DCP with PdCl2, which is a more electron-deficient Pd(II) center, leads to pentachlorinated dinuclear complexes [(Ph-DCP)PdCl2]2Cl-, where the dicoordinate Cl- bridge screens the repelling pairs of positive charges from each other. The same behavior is inferred for the tBu-DCP ligand, from which addition of an excess of (MeCN)2PdCl2 was found to trigger a heterolytic cleavage of the DCP-tBu bond, releasing tBu+ and a dicationic phosphide, DCP-: the latter is evidenced as a ligand in a tetranuclear complex ion [(µ2-DCP-)Pd2Cl4]2, which, upon HCl treatment, dissociates to a doubly zwitterionic dipalladate complex. All the complexes were isolated in 82%-97% yield, and five of them were characterized by X-ray crystallography.

"Carbo-aromaticity" and novel carbo-aromatic compounds.

While the concept of aromaticity is being more and more precisely delineated, the category of "aromatic compounds" is being more and more expanded. This is illustrated by an introductory highlight of the various types of "aromaticity" previously invoked, and by a focus on the recently proposed "aromatic character" of the "two-membered rings" of the acetylene and butatriene molecules. This serves as a general foundation for the definition of "carbo-aromaticity", the relevance of which is surveyed through recent results in the synthetic, physical, and theoretical chemistry of carbo-mers and in particular macrocyclic-polycyclic representatives constituting a natural family of "novel aromatic compounds". With respect to their parent molecules, carbo-mers are constitutionally defined as "carbon-enriched", and can also be functionally regarded as "π-electron-enriched". This is exemplified by recent experimental and theoretical results on functional, aromatic, rigid, σ,π-macrocyclic carbo-benzene archetypes of various substitution patterns, with emphasis on the quadrupolar pattern. For the purpose of comparison, several types of non-aromatic references of carbo-benzenes are then considered, i.e. freely rotating σ,π-acyclic carbo-n-butadienes and flexible σ-cyclic, π-acyclic carbo-cyclohexadienes, and to "pro-aromatic" congeners, i.e. rigid σ,π-macrocyclic carbo-quinoids. It is shown that functional carbo-mers are entering the field of "molecular materials" for properties such as linear or nonlinear optical properties (e.g. dichromism and two-photon absorption) and single molecule conductivity. Since total or partial carbo-mers of aromatic carbon-allotropes of infinite size such as graphene (graphynes and graphdiynes) and graphite ("graphitynes") have long been addressed at the theoretical or conceptual level, recent predictive advances on the electrical, optical and mechanical properties of such carbo-materials are surveyed. Very preliminary experimental results on a carbo-benzenoid fragment are finally disclosed.

carbo-Naphthalene: A Polycyclic carbo-Benzenoid Fragment of α-Graphyne.

A ring carbo-mer of naphthalene, C32 Ar8 (Ar=p-n-pentylphenyl), has been obtained as a stable blue chromophore, after a 19-step synthetic route involving methods inspired from those used in the synthesis of carbo-benzenes, or specifically devised for the present target, like a double Sonogashira-type coupling reaction. The last step is a SnCl2 /HCl-mediated reduction of a decaoxy-carbo-decalin, which is prepared through successive [8+10] macrocyclization steps. Two carbo-benzene references are also described, C18 Ar6 and o-C18 Ar4 (C≡C-SiiPr3 )2 . The carbo-naphthalene bicycle is locally aromatic according to structural and magnetic criteria, as revealed by strong diatropic ring current effects on the deshielding of 1 H nuclei of the Ar groups and on the negative value of the DFT-calculated NICS at the center of the C18 rings (-12.8 ppm). The stability and aromaticity of this smallest fused molecular fragment of α-graphyne allows prediction of the same properties for the carbon allotrope itself.

Chiral alkynylcarbinols from marine sponges: asymmetric synthesis and biological relevance.

Covering: up to March 2014. Previous review on the topic: B. W. Gung, C. R. Chim., 2009, 12, 489-505. Chiral α-functional lipidic propargylic alcohols extracted from marine sponges, in particular of the pacific genus Petrosia, constitute a class of acetylenic natural products exhibiting remarkable in vitro biological activities, especially anti-tumoral cytotoxicity. These properties, associated to functionalities that are uncommon among natural products, have prompted recent projects on asymmetric total synthesis. On the basis of a three-sector structural typology, three main sub-types of secondary alkynylcarbinols (with either alkyl, alkenyl, or alkynyl as the second substituent) can be identified as the minimal pharmacophoric units. Selected natural products containing these functionalities have been targeted using previously known or on purpose-designed procedures, where the stereo-determining step can be: (i) a C-C bond forming reaction (e.g. the Zn-mediated addition of alkynyl nucleophiles to aldehydes in the presence of chiral aminoalcohols), (ii) a functional layout (e.g. the asymmetric organo- or metallo-catalytic reduction of ynones), or (iii) an enantiomeric resolution (e.g. a lipase-mediated kinetic resolution via acetylation). The promising medicinal importance of these targets is finally surveyed, and future investigation prospects are proposed, such as: (i) further total synthesis of known or future extraction products; (ii) the synthesis of non-natural analogues, with simpler lipophilic environments of the alkynylcarbinol-based pharmacophoric units; (iii) the variation and optimization of both the pharmacophoric units and their lipophilic environment; and (iv) investigations into the biological mode of action of these unique structures.

Charge Effects in PCP Pincer Complexes of Ni(II) bearing Phosphinite and Imidazol(i)ophosphine Coordinating Jaws: From Synthesis to Catalysis through Bonding Analysis.

This contribution reports on a new family of Ni(II) pincer complexes featuring phosphinite and functional imidazolyl arms. The proligands (R) PIMC(H) OP(R') react at room temperature with Ni(II) precursors to give the corresponding complexes [((R) PIMCOP(R') )NiBr], where (R) PIMCOP(R) =κ(P) ,κ(C) ,κ(P) -{2-(R'2 PO),6-(R2 PC3 H2 N2 )C6 H3 }, R=iPr, R'=iPr (3 b, 84 %) or Ph (3 c, 45 %). Selective N-methylation of the imidazole imine moiety in 3 b by MeOTf (OTf=OSO2 CF3 ) gave the corresponding imidazoliophosphine [((iPr) PIMIOCOP(iPr) )NiBr][OTf], 4 b, in 89 % yield ((iPr) PIMIOCOP(iPr) =κ(P) ,κ(C) ,κ(P) -{2-(iPr2 PO),6-(iPr2 PC4 H5 N2 )C6 H3 }). Treating 4 b with NaOEt led to the NHC derivative [(NHCCOP(iPr) )NiBr], 5 b, in 47 % yield (NHCCOP(iPr) =κ(P) ,κ(C) ,κ(C) -{2-(iPr2 PO),6-(C4 H5 N2 )C6 H3 )}). The bromo derivatives 3-5 were then treated with AgOTf in acetonitrile to give the corresponding cationic species [((R) PIMCOP(R) )Ni(MeCN)][OTf] [R=Ph, 6 a (89 %) or iPr, 6 b (90 %)], [((R) PIMIOCOP(R) )Ni(MeCN)][OTf]2 [R=Ph, 7 a (79 %) or iPr, 7 b (88 %)], and [(NHCCOP(R) )Ni(MeCN)][OTf] [R=Ph, 8 a (85 %) or iPr, 8 b (84 %)]. All new complexes have been characterized by NMR and IR spectroscopy, whereas 3 b, 3 c, 5 b, 6 b, and 8 a were also subjected to X-ray diffraction studies. The acetonitrile adducts 6-8 were further studied by using various theoretical analysis tools. In the presence of excess nitrile and amine, the cationic acetonitrile adducts 6-8 catalyze hydroamination of nitriles to give unsymmetrical amidines with catalytic turnover numbers of up to 95.

Difluorenyl carbo-Benzenes: Synthesis, Electronic Structure, and Two-Photon Absorption Properties of Hydrocarbon Quadrupolar Chromophores.

The synthesis, crystal and electronic structures, and one- and two-photon absorption properties of two quadrupolar fluorenyl-substituted tetraphenyl carbo-benzenes are described. These all-hydrocarbon chromophores, differing in the nature of the linkers between the fluorenyl substituents and the carbo-benzene core (C-C bonds for 3 a, C-C=C-C expanders for 3 b), exhibit quasi-superimposable one-photon absorption (1PA) spectra but different two-photon absorption (2PA) cross-sections σ2PA. Z-scan measurements (under NIR femtosecond excitation) indeed showed that the C≡C expansion results in an approximately twofold increase in the σ2PA value, from 336 to 656 GM (1 GM = 10(-50) cm(4) s molecule(-1) photon(-1)) at λ = 800 nm. The first excited states of Au and Ag symmetry accounting for 1PA and 2PA, respectively, were calculated at the TDDFT level of theory and used for sum-over-state estimations of σ2PA(λi), in which λi = 2 hc/Ei, h is Planck's constant, c is the speed of light, and Ei is the energy of the 2PA-allowed transition. The calculated σ2PA values of 227 GM at 687 nm for 3 a and 349 GM at 708 nm for 3 b are in agreement with the Z-scan results.

Carbo-benzene's aromaticity, before and beyond: a tribute to Nozoe.

Beyond rigorous inspection of the literature, selected comments and drawings from the Nozoe Autograph Books show how concepts and targets of the chemistry of today already existed 40 years ago. This is illustrated for the chemistry of carbo-mers, which was actually unknowingly inspired by chemists of the golden age. After a personal travel through time and pages by the last author of this essay, who meets autographs by people who have been important in his career, in particular on the occasions of Nozoe's visits to France or past ISNA events, unpublished results in non-benzenoid chemistry are dedicated to Nozoe's memory. Experimental advances are first disclosed on the comparative chemistry of the three ortho, meta and para isomers of tetraphenyl-carbo-benzene C18 H2 Ph4 , the known ortho isomer serving as a reference. The two CH vertices of these chromophores make their [6]pericyclyne precursors quite sensitive and their yields and purifications challenging to optimize. The meta isomer was, however, isolated in 18% yield, and described by NMR and UV-vis absorption spectroscopy and crystallography. The para isomer was characterized both in pure form and in a 1:1 mixture with a single isomer of its HCl adduct, including by X-ray diffraction analysis of a co-crystal showing that the interior of the C18 ring of the HCl adduct is filled by the Cl atom. Theoretical advances are then offered regarding the "aromatic character" of a triple bond, by showing that the topological acyclic reference of acetylene is the Möbius-twisted cyclobutadiene. Acetylenoids are finally proposed as a novel class of non-benzenoid aromatics.

Asymmetric synthesis and biological evaluation of natural or bioinspired cytotoxic C2-symmetrical lipids with two terminal chiral alkynylcarbinol pharmacophores.

Bidirectional syntheses of C2-symmetrical lipids embedding two terminal alkynylcarbinol pharmacophores are reported. Naturally occurring chiral alkenylalkynylcarbinol units were generated using Pu's procedure for enantioselective addition of terminal alkynes to aldehydes, allowing the first asymmetric synthesis of (3R,4E,16E,18R)-icosa-4,16-diene-1,19-diyne-3,18-diol, isolated from Callyspongia pseudoreticulata. Two synthetic analogues embedding the recently uncovered (S)-dialkynylcarbinol pharmacophore were secured using Carreira's procedure adapted to ynal substrates. The dramatic effect of the carbinol configuration on cytotoxicity was confirmed with submicromolar IC50 values against HCT116 cells.