Organic & Biomolecular Chemistry (v.9, #9)

Front cover (3057-3058).

Contents (3059-3079).

The stimulating adventure of KRN 7000 by Aline Banchet-Cadeddu; Eric Hénon; Manuel Dauchez; Jean-Hugues Renault; Fanny Monneaux; Arnaud Haudrechy (3080-3104).
Associated with the CD1d protein, KRN 7000, a potent synthetic α-galactosylceramide, is known to activate the invariant NKT immune cells. This stimulation then leads to the production of different cytokines modulating a TH1/TH2 immune response balance involved in protection against several pathologies such as autoimmune diseases and cancers. Various efforts have been made toward the synthesis of simple and more functionalized analogues in order to selectively induce TH1 or TH2-type cytokine production. Since the discovery of KRN 7000, structure-activity relationships, crystallographic and modelling studies have pointed to the potential of several GalCer analogues in term of selective bioactivity, and have highlighted interesting elements in order to better understand the recognition and activation mechanisms of immune iNKT cells. By presenting an up-to-date library of analogues, collecting recent breakthroughs done in crystallography and molecular modelling, and relating them to the available biological results, we hope that this review will highlight and help the scientific community in their KRN research.

Mannich–Michael versus formal aza-Diels–Alder approaches to piperidine derivatives by P. Ricardo Girling; Takao Kiyoi; Andrew Whiting (3105-3121).
A review into the aza-Diels–Alder reaction, mainly concentrating on literature examples that form piperidin-4-ones from the reaction of imines and electron rich dienes or enones, either through a Lewis acidic/Brønsted acid approach or through the use of an organocatalyst. This review questions whether the mechanism of the aza-Diels–Alder reaction is step wise as opposed to concerted when using oxygenated dienes.

Synthesis of 7-aryl/heteraryl-1,3-diphenyl-1,2,4-benzotriazinyls via palladium catalyzed Stille and Suzuki-Miyaura reactions by Christos P. Constantinides; Panayiotis A. Koutentis; Georgia Loizou (3122-3125).
Stille and Suzuki-Miyaura reactions of 7-iodo-1,3-diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl are presented as rare examples of cross-coupling reactions with stable organic radicals. Both the Stille and Suzuki-Miyaura reactions are in most cases high yielding but the latter are cleaner while the former are faster and are accompanied by 1,3-diphenyl-1,2,4-benzotriazin-7(H)-one as by-product. A range of 7-aryl and 7-heteroaryl-1,2,4-benzotriazinyls have been synthesized and characterized using standard spectroscopic and spectrometric means.

NHC/Iron cooperative catalysis: aerobic oxidative esterification of aldehydes with phenols by R. Sudarshan Reddy; João N. Rosa; Luís F. Veiros; Stephen Caddick; Pedro M. P. Gois (3126-3129).
An NHC/iron cooperative catalytic system mediates the aerobic oxidative esterification of aldehydes with phenols. The use of equimolar amounts of reactants led to good to excellent isolated yields of esters.

Structure elucidation and biosynthesis of lysine-rich cyclic peptides in Xenorhabdus nematophila by Sebastian W. Fuchs; Anna Proschak; Thorsten W. Jaskolla; Michael Karas; Helge B. Bode (3130-3132).
Thirteen novel PAX (peptide-antimicrobial-Xenorhabdus) peptides were identified in Xenorhabdus nematophila HGB081. Their structures including the absolute configuration were elucidated using a combination of labeling experiments, detailed MS/MS experiments, the advanced Marfey's method, and a detailed analysis of the biosynthesis gene cluster, which was identified as well.

A concise and efficient synthesis of benzo[c]phenanthridines was accomplished by the palladium-catalyzed ring-opening coupling of azabicyclic alkene with o-iodobenzoates, followed by tandem cyclization. The strategy was successfully applied in the total synthesis of benzo[c]phenanthridine alkaloids such as sanguinarine, chelerythrine, nitidine and avicine.

Synthetic studies towards marmycins A and B: development of the vinylogous aldol–aza-Michael domino reaction by Emmanuel Bourcet; Manuel C. Bröhmer; Martin Nieger; Stefan Bräse (3136-3138).
The vinylogous aldol–aza-Michael domino reaction between 2-aminobenzaldehydes and prenal was developed to build up the core of natural products marmycin A and B without the need of protective groups.

3-(Hetero)aryl substituted indoles, 7-azaindoles, and pyrroles can be obtained in a very concise fashion via a one-pot Masuda borylation–Suzuki coupling sequence. The concise total syntheses of the marine natural products meridianins A (5) and G (4i) nicely illustrate the utility of this methodology.

CVT + SCT calculations on the rate of tunnelling at 20 K in the ring opening of cyclopropylcarbinyl radical, substituted with geminal methyl groups at a ring carbon (1b), have been performed. The calculations predict that, contrary to expectations based on the effect of mass on the rate of tunnelling, the geminal methyl substituents in 1b should make the rate of ring opening to 1,1-dimethyl-3-butenyl radical (2b) 104 times faster than the rate of ring opening of unsubstituted cyclopropylcarbinyl radical (1a) to 3-butenyl radical (2a) and almost 106 times faster than the rate of ring opening of 1b to 2,2-dimethyl-3-butenyl radical (2c). The reasons for these unexpected findings are discussed.

Titanium chelate addition of aryl nucleophiles to cyclopropyl aldehyde 6 followed by a tin-catalyzed one-pot retro-aldol, acetalisation and lactonisation sequence afforded cis and transγ-aryllactone acetals. A γ-furyllactone derived by this approach was further transformed in two steps to model compounds for the oxidised northeastern sectors of selected Pseudopterogorgia diterpenoids.

Iron-catalyzed sulfonyl radical formations from sulfonylhydrazides and oxidative addition to alkenes by Tsuyoshi Taniguchi; Atsushi Idota; Hiroyuki Ishibashi (3151-3153).
Generation of sulfonyl radicals from sulfonylhydrazides has been achieved in the presence of a non-toxic iron catalyst and oxygen. The intermolecular addition of resultant sulfonyl radicals to alkenes affords β-hydroxysulfone compounds.

Concise syntheses of N-aryl-5,6,7-trimethoxyindoles as antimitotic and vascular disrupting agents: application of the copper-mediated Ullmann-type arylation by Hsueh-Yun Lee; Jang-Yang Chang; Ling-Yin Chang; Wen-Yang Lai; Mei-Jung Lai; Kuang-Hsing Shih; Ching-Chuan Kuo; Chi-Yen Chang; Jing-Ping Liou (3154-3157).
In an attempt to mimic the 3,4,5-trimethoxyphenyl-Z-stilbene moiety of combretastatin A-4, a series of N-aryl-5,6,7-trimethoxyindoles were synthesized via copper-catalyzed Ullmann-type N-arylation through the corresponding 5,6,7-trimethoxyindole and aryl halides. These synthesized compounds demonstrated potent antiproliferative activity providing a novel skeleton for potent tubulin polymerization inhibitors.

The ability of several density-functional theory methods to describe the kinetics and energetics of a series of ring-opening reactions of cyclopropyl and cyclobutyl-type radicals was explored. PBE, B971 and B3LYP perform quite well in their ability to replicate experiment, based upon the ring opening of cyclopropylcarbinyl, two α-trialkylsilyloxycyclopropylmethyl radicals, pentamethylcyclopropylcarbinyl, cyclobutylcarbinyl and 1-cyclobutylethylcarbinyl. The other functionals tested, which includes BLYP, CAM-B3LYP, BHandHLYP, B2PLYP and B2PLYP-D, as well as functionals designed for kinetics applications, namely MPW1K, BMK and M06-2X, all perform poorly. The latter of these functionals display some integration grid dependencies.

Highly efficient and regiospecific photocyclization of 2,2′-diacyl bixanthenylidenes by Mao Mao; Qing-Qing Wu; Ming-Guang Ren; Qin-Hua Song (3165-3169).
In contrast to the reversible photochemistry of the 2,2′-substituted bixanthenylidenes (1a–f), the photocyclization of 2,2′-diacyl bixanthenylidenes (1g–j) reveals an irreversible process where the initial cyclic intermediate C(E) can undergo a rapid [1,11] hydrogen shift to form stable isomer C′(E) in a degassed solution, which cannot revert to the starting compound, so giving a highly efficient and regiospecific photocyclization.

Unprecedented stereoselective synthesis of cyclopenta[b]benzofuran derivatives and their characterisation assisted by aligned media NMR and 13C chemical shift ab initio predictions by Martín J. Riveira; Chakicherla Gayathri; Armando Navarro-Vázquez; Nicolay V. Tsarevsky; Roberto R. Gil; Mirta P. Mischne (3170-3175).
A new approach to the synthesis of cyclopenta[b]benzofuran derivatives via reaction of 1,3-dicarbonyl compounds with α,β,γ,δ-unsaturated aldehydes is described. The constitution and configuration of the new products have been firmly established by means of residual dipolar couplings (RDCs) and ab initio13C NMR chemical shift predictions.

The total synthesis of a trans-position butenolide analogue of triptolide 3 and the semi-synthesis of analogue 4, with a furan ring, and compound 5, without a planar D-ring, are described. Studies into the antitumor activity of these compounds suggest that the five-membered unsaturated lactone ring (D-ring) of triptolide is essential to its potent anticancer activity and the C18 carbonyl group may exert an important influence on the interaction between triptolide and the target molecule(s) responsible for initiating their cytotoxic effects.

Translocation versus cyclisation in radicals derived from N-3-alkenyl trichloroacetamides by M. Luisa Marin; Ramon J. Zaragoza; Miguel A. Miranda; Faïza Diaba; Josep Bonjoch (3180-3187).
Under radical reaction conditions, two different and competitive reaction pathways were observed for N-(α-methylbenzyl)trichloroacetamides with a N-3-cyclohexenyl substituent: 1,4-hydrogen translocation and radical addition to a double bond. However, for radicals with an acyclic alkenyl side chain, the direct cyclisation process was exclusively observed. The dichotomy between translocation and direct radical cyclisation in these substrates has been theoretically studied using density functional theory (DFT) methods at the B3LYP/6-31G** computational level.

A series of light-activatable perfluorophenylazide (PFPA)-conjugated carbohydrate structures have been synthesized and applied to glycoarray fabrication. The glycoconjugates were structurally varied with respect to anomeric attachment, S-, and O-linked carbohydrates, respectively, as well as linker structure and length. Efficient stereoselective synthetic routes were developed, leading to the formation of the PFPA-conjugated structures in good yields over few steps. The use of glycosyl thiols as donors proved especially efficient and provided the final compounds in up to 70% total yield with high anomeric purities. PFPA-based photochemistry was subsequently used to generate carbohydrate arrays on a polymeric surface, and surface plasmon resonance imaging (SPRi) was applied for evaluation of carbohydrate-protein interactions using the plant lectin Concanavalin A (Con A) as a probe. The results indicate better performance and equal efficiency of S- and O-linked structures with intermediate linker length.

Radical-based grafting of GMA on sutures of different nature by Angelo Alberti; Piergiorgio Fuochi; Maurizio Guerra; Dante Macciantelli; Giangiacomo Torri; Antonio Valerio; Elena Vismara (3199-3204).
Irradiation of a number of different sutures largely employed in the clinical practice with either high energy electrons or with γ-rays followed by quenching with glycidyl methacrylate (GMA) conveniently led to derivatization through a radical-based process. The radicals involved were detected by means of ESR spectroscopy and were characterized on the basis of their ESR spectral parameters which were also found to be consistent with the hfs constants predicted by DFT calculations. Evidence of the GMA derivatization of the sutures was obtained via13C CP-MAS NMR spectroscopy, while its extent was evaluated gravimetrically.

Synthesis and antiproliferative evaluation of 2,3-diarylquinoline derivatives by Chih-Hua Tseng; Yeh-Long Chen; Kuin-Yu Chung; Chi-Huei Wang; Shin-I Peng; Chih-Mei Cheng; Cherng-Chyi Tzeng (3205-3216).
A number of 2,3-diarylquinoline derivatives were synthesized and evaluated for antiproliferative activities against the growth of six cancer cell lines including human hepatocellular carcinoma (Hep G2 and Hep 3B), non-small cell lung cancer (A549 and H1299), and breast cancer (MCF-7 and MDA-MB-231) cell lines. The preliminary results indicated that 6-fluoro-2,3-bis{4-[2-(piperidin-1-yl)ethoxy]phenyl}quinoline (16b) was one of the most active compounds against the growth of Hep 3B, H1299, and MDA-MB-231 with a GI50 value of 0.71, 1.46, and 0.72 μM respectively which was more active than tamoxifen. Further investigations have shown that 16b induced cell cycle arrest at G2/M phase followed by DNA fragmentation via an increase in the protein expression of Bad, Bax and decrease in Bcl-2, and PARP which consequently cause cell death.

An ab initio and DFT study of radical addition reactions of imidoyl and thioyl radicals to methanimine by Sara H. Kyne; Carl H. Schiesser; Hiroshi Matsubara (3217-3224).
Ab initio and DFT calculations reveal that both imidoyl and thioyl radicals add to the nitrogen end of methanimine through simultaneous SOMO-π*imine, SOMO-πimine, SOMO-LPN and π*radical-LPN interactions between the radical and the imine. At the CCSD(T)/cc-pVDZ//BHandHLYP/cc-pVTZ level of theory, barriers of 13.8 and 26.1 kJ mol−1 are calculated for the attack of the methylimidoyl radical at the carbon- and nitrogen- end of methanimine, respectively, indicating that the imidoyl radial has a preference for addition to the nitrogen end of imine. On the other hand, barriers of 25.1 and 13.4 kJ mol−1 are calculated at the same level of theory for the addition reaction of the methanethioyl radical at the carbon- and nitrogen- end of methanimine, respectively. Natural bond orbital (NBO) analysis at the BHandHLYP/6-311G** level of theory reveals that SOMO-π*imine, SOMO-πimine, SOMO-LPN and π*radical-LPN interactions are worth 111, 89, 115 and 17 kJ mol−1, respectively, in the transition state (4) for the reaction of methylimidoyl radical at the nitrogen end of methanimine; similar interactions are observed for the chemistry involving all the radicals studied here. These multi-component interactions are responsible for the unusual motion vectors associated with the transition states involved in these reactions.

p-tert-Butyl thiacalix[4]arenes functionalized at the lower rim by amide, hydroxyl and ester groups as anion receptors by Ivan I. Stoikov; Alena A. Yantemirova; Roman V. Nosov; Ildar Kh. Rizvanov; Ajdar R. Julmetov; Vladimir V. Klochkov; Igor S. Antipin; Alexander I. Konovalov; Ilya Zharov (3225-3234).
New p-tert-butyl thiacalix[4]arenes differently substituted at the lower rim with amide, hydroxyl and ester groups were synthesized. Binding properties of the compounds toward some tetrabutylammonium salts n-Bu4NX (X = F, Cl, Br, I, CH3CO2, H2PO4, NO3) were studied by UV spectroscopy. It was found that the stoichiometry of the complexes, generally, is 1 : 1, and the association constants are in the range of 103–105 M−1. The p-tert-butyl thiacalix[4]arenes containing secondary amide groups trisubstituted at the lower rim bind the studied anions most effectively. Selective receptors for fluoride and dihydrogen phosphate salts of tetrabutylammonium were found.

Tandem regioselective synthesis of tetrazoles and related heterocycles using iodine by Ramesh Yella; Nilufa Khatun; Saroj Kumar Rout; Bhisma K. Patel (3235-3245).
A one-pot, tandem process has been developed for the synthesis of a library of tetrazoles from aryl isothiocyanates. Condensation of aryl isothiocyanates with ammonia, and aryl amines (R-NH2) provided mono, 1,3-disubstituted symmetrical and unsymmetrical thioureas, which on desulfurization with molecular iodine (I2) led to formation of the corresponding heterocumulene (cyanamides or carbodiimides). The in situ generated heterocumulene on subsequent treatment with sodium azide at room temperature gave corresponding tetrazoles. The product regioselectivity for unsymmetrical 1,3-disubstituted thioureas was found to be correlated with the basicities (pKa's) of the parent amines attached to the thiourea. Aryl-sec-alkyl unsymmetrical thioureas gave thioamido guanidino products rather than the 5-aminotetrazoles produced by HgCl2 mediation of the reaction. Bis-thioureas derived from aryl isothiocyanates and hydrazine gave thiadiazoles exclusively.

Design, synthesis and biological characterization of novel inhibitors of CD38 by Min Dong; Yuan-Qi Si; Shuang-Yong Sun; Xiao-Ping Pu; Zhen-Jun Yang; Liang-Ren Zhang; Li-He Zhang; Fung Ping Leung; Connie Mo Ching. Lam; Anna Ka Yee Kwong; Jianbo Yue; Yeyun Zhou; Irina A. Kriksunov; Quan Hao; Hon Cheung Lee (3246-3257).
Human CD38 is a novel multi-functional protein that acts not only as an antigen for B-lymphocyte activation, but also as an enzyme catalyzing the synthesis of a Ca2+ messenger molecule, cyclic ADP-ribose, from NAD+. It is well established that this novel Ca2+ signaling enzyme is responsible for regulating a wide range of physiological functions. Based on the crystal structure of the CD38/NAD+ complex, we synthesized a series of simplified N-substituted nicotinamide derivatives (Compound1–14). A number of these compounds exhibited moderate inhibition of the NAD+ utilizing activity of CD38, with Compound4 showing the highest potency. The crystal structure of CD38/Compound4 complex and computer simulation of Compound7 docking to CD38 show a significant role of the nicotinamide moiety and the distal aromatic group of the compounds for substrate recognition by the active site of CD38. Biologically, we showed that both Compounds4 and 7 effectively relaxed the agonist-induced contraction of muscle preparations from rats and guinea pigs. This study is a rational design of inhibitors for CD38 that exhibit important physiological effects, and can serve as a model for future drug development.

Synthesis of tri-substituted biaryl based trianglimines: formation of C3-symmetrical and non-symmetrical regioisomers by Hany F. Nour; Marius F. Matei; Bassem S. Bassil; Ulrich Kortz; Nikolai Kuhnert (3258-3271).
2-Functionalised aromatic monoaldehydes were synthesised in good to excellent yields by reacting 4-bromo-2-fluorobenzaldehyde with different secondary amines and phenol. The Suzuki-coupling reaction of the newly functionalised aromatic monoaldehydes with 4-formylphenylboronic acid afforded the corresponding 2-functionalised-4,4′-biphenyldialdehydes in good yields (47–85%). The [3+3]-cyclocondensation reactions of the 2-functionalised-4,4′-biphenyldialdehydes with (1R,2R)-1,2-diaminocyclohexane afforded a mixture of regioisomeric C3-symmetrical and non-symmetrical trianglimines. Reduction of the C3-symmetrical and the non-symmetrical trianglimines with NaBH4 in a mixture of THF and MeOH afforded the corresponding trianglamines in high yields.

Hirsutosterols A–G, polyoxygenated steroids from a Formosan soft coral Cladiella hirsuta by Bo-Wei Chen; Shu-Ming Chang; Chiung-Yao Huang; Jui-Hsin Su; Zhi-Hong Wen; Yang-Chang Wu; Jyh-Horng Sheu (3272-3278).
Seven new polyoxygenated steroids, hirsutosterols A–G (1–7), were isolated from the Formosan soft coral Cladiella hirsuta. Their structures were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The absolute configurations of 1 and 5 were determined by Mosher's method. Sterols 4–6 possess hydroxy groups at C-9 and C-11 and might be oxidatively cleaved to the corresponding 9,11-secosterols. Hirsutosterol A (1) was found to exhibit a stronger cytotoxicity against a limited panel of cancer cell lines.

A quantitative structure-reactivity relationship in N-acetyl oxazolidines: an electrostatic interaction controls rotamer population by R. Fernando Martínez; Martín Ávalos; Reyes Babiano; Pedro Cintas; José L. Jiménez; Juan C. Palacios; Esther M. S. Pérez (3279-3289).
The conformational population of Z and E isomers of the amide bond in N-acetyl oxazolidines is dictated by the electronic nature of the vicinal aryl ring. Experimental and theoretical data support a rationale based on a strong and stereodirecting charge–charge interaction that should be added to the arsenal of non-covalent interactions and whose influence can be more important than once thought.

The importance of the N–H bond in Ru/TsDPEN complexes for asymmetric transfer hydrogenation of ketones and imines by Rina Soni; Fung Kei Cheung; Guy C. Clarkson; Jose E. D. Martins; Mark A. Graham; Martin Wills (3290-3294).
Ru(ii) complexes of TsDPEN containing two alkyl groups on the non-tosylated nitrogen atom are poor catalysts for asymmetric transfer hydrogenation of ketones and imines; this observation provides direct evidence for the importance of the N–H interaction in the transition state for ketone reduction.

Novel carbohydrate-based bifunctional organocatalysts for nucleophilic addition to nitroolefins and imines by Alessandra Puglisi; Maurizio Benaglia; Laura Raimondi; Luigi Lay; Laura Poletti (3295-3302).
Glucosamine has been selected as a cheap and readily available chiral scaffold for the synthesis of a series of novel enantiomerically pure bifunctional organocatalysts bearing a tertiary amino group in proximity to a (thio)urea group. The catalytic behaviour of these compounds, both as neutral and N-protonated species, was investigated using the addition of acetylacetone to β-nitrostyrene as a model reaction. Under optimized experimental conditions, chemical yields up to 93% and enantioselectivities up to 89% were obtained. Semiempirical (AM1) computational studies allowed to find a theoretical rationale for the chemical and stereochemical behaviour of the catalyst of choice. These catalysts were also preliminarily investigated as promoters in the addition of diethyl malonate to the N-Boc imine of benzaldehyde, affording the product in up to 81% ee.

Conformational studies on peptides containing α,α-disubstituted α-amino acids: chiral cyclic α,α-disubstituted α-amino acid as an α-helical inducer by Yosuke Demizu; Mitsunobu Doi; Masaaki Kurihara; Haruhiro Okuda; Masanobu Nagano; Hiroshi Suemune; Masakazu Tanaka (3303-3312).
Four types of α,α-disubstituted amino acids {i.e., α-aminoisobutyric acid (Aib), 1-aminocyclopentanecarboxylic acid (Ac5c), (3S,4S)-1-amino-(3,4-dimethoxy)cyclopentanecarboxylic acid [(S,S)-Ac5cdOM] and its enantiomer (R,R)-Ac5cdOM} were introduced into l-leucine-based hexapeptides and nonapeptides. The dominant conformations of eight peptides: Cbz-(l-Leu-l-Leu-dAA)2-OMe [dAA = 1: Aib; 2: Ac5c; 3: (S,S)-Ac5cdOM; 4: (R,R)-Ac5cdOM] and Boc-(l-Leu-l-Leu-dAA)3-OMe [dAA = 5: Aib; 6: Ac5c; 7: (S,S)-Ac5cdOM; 8: (R,R)-Ac5cdOM], were investigated by IR, CD spectra and X-ray crystallographic analysis. The CD spectra revealed that Aib hexapeptide 1 and Ac5c hexapeptide 2 formed right-handed (P) 310-helices, while Ac5cdOM hexapeptides 3 and 4 formed a mixture of (P) 310- and α-helices. The Aib nonapeptide 5 formed a (P) 310-helix, the Ac5c nonapeptide 6 formed a mixture of (P) 310- and α-helices, and the Ac5cdOM nonapeptides 7 and 8 formed (P) α-helices. X-Ray crystallographic analysis revealed that the Aib hexapeptide 1 formed a (P) 310-helix, while (S,S)-Ac5cdOM hexapeptide 3 formed a (P) α-helix. In addition, the Ac5c nonapeptide 6 and (R,R)-Ac5cdOM nonapeptide 8 formed (P) α-helices. The Aib and achiral Ac5c residues have the propensity to form 310-helices in short peptides, whereas the chiral Ac5cdOM residues have a penchant for forming α-helices.

Microfluidic reactions using [11C]carbon monoxide solutions for the synthesis of a positron emission tomography radiotracer by Steven Kealey; Christophe Plisson; T. Lee Collier; Nicholas J. Long; Stephen M. Husbands; Laurent Martarello; Antony D. Gee (3313-3319).
Microfluidic technology has been used to perform [11C]carbonylation reactions using solutions containing [11C]CO in the form of the complex, copper(i)tris(3,5-dimethylpyrazolyl)borate-[11C]carbonyl (Cu(Tp*)[11C]CO). The synthesis of the model compound [11C]N-benzylbenzamide and the known tracer molecule [11C]trans-N-[5-(2-flurophenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofurane-1(3H),1′-cyclohexane]-4′-carboxamide ([11C]MK-0233), a ligand for the neuropeptide Y Y5 receptor, have been performed using this technique. Following semi-preparative HPLC purification and reformulation, 1262 ± 113 MBq of [11C]MK-0233 was produced at the end of the synthesis with a specific activity of 100 ± 30 GBq μmol−1 and a >99% radiochemical purity. This corresponds to a decay corrected radiochemical yield of 7.2 ± 0.7%. Using a 3 mL vial as the reaction vessel, and following semi-preparative HPLC purification and reformulation, 1255 ± 392 MBq of [11C]MK-0233 was produced at the end of the synthesis with a specific activity of 100 ± 15 GBq μmol−1 and a >99% radiochemical purity. This corresponds to a decay corrected radiochemical yield of 7.1 ± 2.2%.

The mechanism of radical-trapping antioxidant activity of plant-derived thiosulfinates by Philip T. Lynett; Krista Butts; Vipraja Vaidya; Graham E. Garrett; Derek A. Pratt (3320-3330).
It has long been recognized that garlic and petiveria, two plants of the Allium genus—which also includes onions, leeks and shallots—possess great medicinal value. In recent times, the biological activities of extracts of these plants have been ascribed to the antioxidant properties of the thiosulfinate secondary metabolites allicin and S-benzyl phenylmethanethiosulfinate (BPT), respectively. Herein we describe our efforts to probe the mechanism of the radical-trapping antioxidant activity of these compounds, as well as S-propyl propanethiosulfinate (PPT), a saturated analog representative of the thiosulfinates that predominate in non-medicinal alliums. Our experimental results, which include thiosulfinate-inhibited autoxidations of the polyunsaturated fatty acid (ester) methyl linoleate, investigations of their decomposition kinetics, and radical clock experiments aimed at obtaining some quantitative insights into their reactions with peroxyl radicals, indicate that the radical-trapping activity of thiosulfinates is paralleled by their propensity to undergo Cope elimination to yield a sulfenic acid. Since sulfenic acids are transient species, we complement our experimental studies with the results of theoretical calculations aimed at understanding the radical-trapping behaviour of the sulfenic acids derived from allicin, BPT and PPT, and contrasting the predicted thermodynamics and kinetics of their reactions with those of the parent thiosulfinates. The calculations reveal that sulfenic acids have among the weakest O–H bonds known (ca. 70 kcal mol−1), and that their reactions with peroxyl radicals take place by a near diffusion-controlled proton-coupled electron transfer mechanism. As such, it is proposed that the abundance of a thiosulfinate in a given plant species, and the ease with which it undergoes Cope elimination to form a sulfenic acid, accounts for the differences in antioxidant activity, and perhaps medicinal value, of extracts of these plants. Interestingly, while the Cope elimination of 2-propenesulfenic acid from allicin is essentially irreversible, the analogous reaction of BPT is readily reversible. Thus, in the absence of chain-carrying peroxyl radicals (or other appropriately reactive trapping agent), BPT is reformed.

Intramolecular homolytic substitution of sulfinates and sulfinamides – a computational study by Sara H. Kyne; Heather M. Aitken; Carl H. Schiesser; Emmanuel Lacôte; Max Malacria; Cyril Ollivier; Louis Fensterbank (3331-3337).
Ab initio and density functional theory (DFT) calculations predict that intramolecular homolytic substitution by alkyl radicals at the sulfur atom in sulfinates proceeds through a smooth transition state in which the attacking and leaving radicals adopt a near collinear arrangement. When forming a five-membered ring and the leaving radical is methyl, G3(MP2)-RAD//ROBHandHLYP/6-311++G(d,p) calculations predict that this reaction proceeds with an activation energy (ΔE1) of 43.2 kJ mol−1. ROBHandHLYP/6-311++G(d,p) calculations suggest that the formation of five-membered rings through intramolecular homolytic substitution by aryl radicals at the sulfur atom in sulfinates and sulfinamides, with expulsion of phenyl radicals, proceeds with the involvement of hypervalent intermediates. These intermediates further dissociate to the observed products, with overall energy barriers of 45–68 kJ mol−1, depending on the system of interest. In each case, homolytic addition to the phenyl group competes with substitution, with calculated barriers of 51–78 kJ mol−1. This computational study complements and provides insight into previous experimental observations.

Reactive oxygen species attack both base and sugar moieties in DNA with a preference among the bases for reaction at guanine. In the present study, 2′-deoxyguanosine (dG) was oxidized by a copper-mediated Fenton reaction with the reductants ascorbate or N-acetyl-cysteine, yielding oxidation on both the base and the sugar. The primary oxidized lesions observed in these studies include the 2′-deoxyribonucleosides of 8-oxo-7,8-dihydroguanosine (dOG), spiroiminodihydantoin (dSp), guanidinohydantoin (dGh), oxazolone (dZ), and 5-carboxamido-5-formamido-2-iminohydantoin (d2Ih), as well as the free base guanine. d2Ih was the major product observed in the nucleoside, single- and double-stranded oligodeoxynucleotide contexts and is proposed to arise from oxidation at C5 of guanine. Product distribution studies provide insight into the role of the reductant in partitioning of dG base oxidation along the C5 and C8 pathways.

Multifunctional chiral phosphine (phosphine–thiourea type) L2-catalyzed allylic substitutions of MBH adducts 1 with oxazolones 2 produce the corresponding optically active adducts 3 in good to excellent yields and ee's as well as moderate to good de's under mild conditions. The synergistic interaction between hydrogen bond donor site and nucleophilic site has been discussed, indicating that finely tuning the active sites of the multifunctional phosphine organocatalysts is very important.

Titanium-mediated rearrangement of cyclopropenylmethyl acetates to (E)-halodienes by Gary Gallego; Alireza Ariafard; Kiet Tran; David Sandoval; Leera Choi; Yi-Hsun Chen; Brian F. Yates; Fu-Ming Tao; Christopher J. T. Hyland (3359-3363).
TiCl4 and TiBr4 rapidly transform cyclopropenylmethyl acetates to (E)-halodienes via ring-opening to allyl-vinyl cations. DFT calculations suggest that the regioselectivity of the halogenation of this cationic intermediate by [TiX4OAc] is under thermodynamic control, while the stereoselectivity is governed by kinetics.

Reductive biotransformation of nitroalkenes via nitroso-intermediates to oxazetes catalyzed by xenobiotic reductase A (XenA) by Katharina Durchschein; Walter M. F. Fabian; Peter Macheroux; Klaus Zangger; Gregor Trimmel; Kurt Faber (3364-3369).
A novel reductive biotransformation pathway for β,β-disubstituted nitroalkenes catalyzed by flavoproteins from the Old Yellow Enzyme (OYE) family was elucidated. It was shown to proceed via enzymatic reduction of the nitro-moiety to furnish the corresponding nitroso-alkene, which underwent spontaneous (non-enzymatic) electrocyclization to form highly strained 1,2-oxazete derivatives. At elevated temperatures the latter lost HCN via a retro-[2 + 2]-cycloaddition to form the corresponding ketones. This pathway was particularly dominant using xenobiotic reductase A, while pentaerythritol tetranitrate-reductase predominantly catalyzed the biodegradation via the Nef-pathway.

Copper catalyzed [3+2] cycloaddition “click method” provided an efficient and high yielding immobilization of cobalt(ii) Schiff base to the azido-functionalized MeOPEG5000; whereas the direct reaction between MeOPEG5000 and Co(ii) Schiff base did not produce any immobilization. The prepared catalyst was tested for the oxidative dehydrogenation of various secondary amines using TBHP as oxidant and could be easily recovered by precipitation with diethyl ether at the end of the reaction.

A variety of substituted 4H-pyrans are readily prepared in moderate to good yields under the mild reaction conditions by nucleophilic addition to electron-deficient 1,3-conjugated enynes with phase-transfer catalysis (PTC).

Damage of aromatic amino acids by the atmospheric free radical oxidant NO3˙ in the presence of NO2˙, N2O4, O3 and O2 by Catrin Goeschen; Natalia Wibowo; Jonathan M. White; Uta Wille (3380-3385).
Analysis of the products formed in the reaction of NO3˙ with the N- and C-protected aromatic amino acids 1–5, which was performed under conditions that simulate exposure of biosurfaces to environmental pollutants, revealed insight how this important atmospheric free-radical oxidant can cause irreversible damage. In general, NO3˙ induced electron transfer at the aromatic ring is the exclusive initial pathway in a multi-step sequence, which ultimately leads to nitroaromatic compounds. In the reaction of NO3˙ with tryptophan 5 tricyclic products 12 and 13 are formed through an intramolecular, oxidative cyclization involving the amide moiety. In addition to this, strong indication for formation of N-nitrosamides was obtained, which likely result from reaction with N2O4 through an independent non-radical pathway.

Novel pyrrolidine-thiohydantoins/thioxotetrahydropyrimidinones as highly effective catalysts for the asymmetric Michael addition by Christoforos G. Kokotos; Dimitris Limnios; Despoina Triggidou; Maria Trifonidou; George Kokotos (3386-3395).
The synthesis of novel organocatalysts consisting of a pyrrolidine moiety and a thiohydantoin or a thioxotetrahydropyrimidinone ring is described. The compound combining the pyrrolidine with the thioxotetrahydropyrimidinone was found to be a highly effective catalyst for the Michael reaction. Low catalyst loadings (1–2.5%) can be employed leading to quantitative yields and excellent stereoselectivities in the reaction between cyclic ketones and nitroolefins.

Cis- and trans-decalins, trans-perhydroazulenes, and [5.3.1]-bicyclo-undecanone scaffolds can be readily constructed starting from unsaturated ketones and using the degenerative xanthate transfer technology to accomplish unusual and otherwise difficult radical cyclisations.

l-DMDP, l-homoDMDP and their C-3 fluorinated derivatives: synthesis and glycosidase-inhibition by Yi-Xian Li; Mu-Hua Huang; Yukiko Yamashita; Atsushi Kato; Yue-Mei Jia; Wu-Bao Wang; George W. J. Fleet; Robert J. Nash; Chu-Yi Yu (3405-3414).
l-DMDP and l-homoDMDP, the enantiomers of naturally occurring DMDP and homoDMDP have been synthesized from d-xylose derived cyclic nitrone 9. Their 3-deoxy-3-fluorinated analogues were also obtained from polyhydroxylated fluorinated cyclic nitrone 10, which was prepared from fluorinated sugar 12 in seven steps. Bioactivities of these iminosugars against various glycosidases were evaluated. While l-DMDP and l-homoDMDP are potent inhibitors of α-glucosidases, a sharp decrease of inhibition was found when the C-3 hydroxyl group of these compounds was replaced by fluoride, which showed the great importance of the C-3 hydroxyl in their interaction with enzymes.

Radical reductions of alkyl halides bearing electron withdrawing groups with N-heterocyclic carbene boranes by Shau-Hua Ueng; Louis Fensterbank; Emmanuel Lacôte; Max Malacria; Dennis P. Curran (3415-3420).
1,3-Dimethylimidazol-2-ylidene borane and 2,4-dimethyl-1,2,4-triazol-3-ylidene borane are found to be useful reagents for the reduction of alkyl iodides and bromides bearing nearby electron withdrawing substituents. Signatures of radical chain reactions are seen in many cases, but ionic reductions may also be occurring with some substrates. The reagents are attractive because of their low molecular weight, their availability from inexpensive precursors, and their stability. Separation of the borane products from the target products is readily accomplished either with or without prior regeneration of the borane for later reuse. 2,4-Dimethyl-1,2,4-triazol-3-ylidene borane is versatile because both starting borane and its derived products can be removed by extraction with water.

Design and synthesis of amidine-type peptide bond isosteres: application of nitrile oxide derivatives as active ester equivalents in peptide and peptidomimetics synthesis by Eriko Inokuchi; Ai Yamada; Kentaro Hozumi; Kenji Tomita; Shinya Oishi; Hiroaki Ohno; Motoyoshi Nomizu; Nobutaka Fujii (3421-3427).
Amidine-type peptide bond isosteres were designed based on the substitution of the peptide bond carbonyl (CO) group with an imino (CNH) group. The positively-charged property of the isosteric part resembles a reduced amide-type peptidomimetic. The peptidyl amidine units were synthesized by the reduction of a key amidoxime (N-hydroxyamidine) precursor, which was prepared from nitrile oxide components as an aminoacyl or peptidyl equivalent. This nitrile oxide-mediated C–N bond formation was also used for peptide macrocyclization, in which the amidoxime group was converted to peptide bonds under mild acidic conditions. Syntheses of the cyclic RGD peptide and a peptidomimetic using both approaches, and their inhibitory activity against integrin-mediated cell attachment, are presented.

An efficient synthesis of dihydro- and tetrahydropyrans via oxonium–ene cyclization reaction by Somasekhar Bondalapati; Udagandla C. Reddy; Pipas Saha; Anil K. Saikia (3428-3438).
An efficient method has been developed for the synthesis of 2,3-dihydropyrans and 4-methylenetetrahydropyrans from aldehydes and substituted homoallyl alcohols in benzene mediated by boron trifluoride etherate in good yields. The reaction proceeds via oxonium–ene reaction.

An efficient double bond migration–ring closing metathesis reaction leading to cycloheptene derivatives is observed when specific sterically congested 1,9-dienes are treated with the Grubbs' imidazolidene ruthenium catalyst. The simultaneous use of the Grubbs' catalyst and RuClH(CO)(PPh3)3 facilitates the tandem bond migration–metathesis process. RuClH(CO)(PPh3)3 alone is capable of triggering an unactivated double bond migration that may have preparative applications.

Vinylogous anionic processes in the formation and interconversion of tetracyclic ring systems by Paul D. Thornton; T. Stanley Cameron; D. Jean Burnell (3447-3456).
Tandem oxy-Cope and transannular vinylogous aldol reactions and/or vinylogous retro-aldol, conjugate addition, and transannular vinylogous aldol reactions transformed some tricyclic vinyl enones into fused tetracycles under basic conditions. Mesylates derived from similar tetracyclic products underwent efficient skeletal reorganization via transannular ring-opening but then different modes of transannular ring-closure upon treatment with tert-butoxide.

Novel one-pot process for the synthesis of 1,3-thiazoles via organocatalysed epoxidation of nitro-olefins by Katharina M. Weiß; Shengwei Wei; Svetlana B. Tsogoeva (3457-3461).
A facile one-pot two-step process for the synthesis of 1,3-thiazole heterocycles via organocatalytic epoxidation of nitro-olefins with the t-BuOOH/DBU system, and subsequent reaction of α-nitro-epoxides with thioamides under mild conditions has been developed.

Water-soluble amino derivatives of free-base dppz – syntheses and DNA binding studies by Tim Phillips; Itshamul Haq; Jim A. Thomas (3462-3470).
The syntheses of two water soluble dipyrido-[3,2-a:2′,3′-c]-phenazine analogues containing one or two appended amino/amide chains are reported. Steady state optical studies on the two new compounds reveal high-energy dppz-based luminescence in water and non-aqueous solvents. Optical titrations with duplex DNA show that the luminescence is quenched on the addition of DNA. Binding curves constructed from absorption and emission changes indicate that, while one of the compounds display negligible binding properties, the other binds DNA with relatively high affinity (>105 M− 1). Isothermal calorimetry experiments, designed to investigate the higher binding compound in more detail, reveals that its interaction with CT-DNA is actually biphasic with one tight (>105 M− 1) and one weaker binding site (∼105 M− 1). In both cases binding is entropically driven. Further calorimetry studies involving the interaction of the new compound with a variety of polynucleotides were carried out. To aid comparisons, similar experiments involving a previously reported bipyridyldiylium derivative of dppz were also carried out. These studies reveal that the bipyridyldiylium derivative binds all these sequences monophasically with relatively low affinities (∼104 M− 1). However, while the amino/amide chain appended derivative binds to Poly(dA).poly(dT) monophasically with relatively low affinities, it binds all the other polynucleotide studied biphasically, with affinities ranging from <106 M− 1 to >108 M− 1. The ITC data reveals that for both compounds thermodynamic signatures for binding are dependent on the sequence being bound. In both cases, the data for Poly(dA).poly(dT) is particularly anomalous. An analysis of the data shows that binding is selective, with affinities at flexible sequences being several orders of magnitude higher than those at more rigid sequences.

Synthesis of a family of cyclic peptide-based anion receptors by Stephen J. Butler; Katrina A. Jolliffe (3471-3483).
We report here the design and synthesis of a family of novel backbone modified cyclic peptides, bearing dipicolylamine side chains for metal complexation and subsequent anion binding studies. Two approaches to the cyclic peptides were investigated. Initially, a stepwise approach was employed, involving solid-phase assembly of oxazole-based building blocks, followed by solution-phase macrolactamisation of the resulting linear precursor. The alternative strategy involved the formation of linear bisoxazole fragments in solution-phase, followed by a cyclodimerisation reaction. The zinc(ii) complexes of these receptors bind selectively to di- and tri-phosphate ions over hydrogenphosphate.

A synthesis of the structure reported for the natural product crassiflorone, a furocoumarin naphthoquinone, is described. The key steps are a Diels–Alder reaction to form 2-bromo-8-hydroxy-6-methylnaphthoquinone, followed by O-protection and copper(ii) mediated coupling to 4-hydroxy-5-methylcoumarin to establish the pentacyclic framework whose structure was unambiguously confirmed by X-ray crystallography. Since the spectroscopic data of the synthetic material did not match those reported for the natural product, three further regioisomeric furocoumarin naphthoquinones were prepared by copper(ii) mediated coupling of 4-hydroxy-5- or 8-methyl coumarins with 5-benzyloxy-2-bromo-7-methyl- or 8-benzyloxy-2-bromo-6-methyl-1,4-naphthoquinone. Again the spectroscopic data did not match those of the natural material and therefore the true structure of crassiflorone remains unknown.

Radical-based alkylation of guanine derivatives in aqueous medium by Chryssostomos Chatgilialoglu; Clara Caminal; Quinto G. Mulazzani (3494-3498).
The radical-based alkylation of 8-bromoguanosine (1a) and 8-bromo-2′-deoxyguanosine (1b) at the C8 position has been investigated in aqueous solutions. Alkyl radicals were generated by scavenging of the primary species of γ-radiolysis by the alcohol substrate. These reactions result in the efficient formation of intermolecular C–C bonds in aqueous media, by using the reactivity of α-hydroxyalkyl radicals derived from alcohols with 1a and 1b. A mechanism for the formation of C8 guanine alkylated adducts has been proposed, based on the quantification of radiation chemical yields for the disappearance of starting material and the formation of all products. Two α-hydroxyalkyl radicals are needed to form an alkylated guanine, the first one adding to C8 followed by ejection of Br with formation of guanyl adduct and the second one acting as reducing agent of the guanyl adduct.

Rapid carbonylative coupling reactions using palladium(i) dimers: applications to 11CO-radiolabelling for the synthesis of PET tracers by Gabriella Buscemi; Philip W. Miller; Steven Kealey; Antony D. Gee; Nicholas J. Long; Jan Passchier; Ramon Vilar (3499-3503).
Palladium dimers with sterically hindered phosphines have been shown to be excellent pre-catalysts for the aminocarbonylation of aryl halides to yield amides and one of them has been successfully employed as a pre-catalyst for the synthesis of 11C-radiolabelled amides for PET imaging.

We report the template-directed synthesis of a well-defined, kinetically stable [5]molecular necklace with dialkylammonium ion (R2NH2+) as recognition site and DB24C8 as macrocycle. A thread containing four dialkylammonium ions with olefin at both ends was first synthesized and then subjected to threading with an excess amount of DB24C8 to form pseudo[5]rotaxane, which in situ undergoes ring closing metathesis at the termini with second generation Grubbs catalyst to yield the desired [5]molecular necklace. The successful synthesis of [5]molecular necklace is mainly attributed to the self-assembly and dynamic covalent chemistry which allows the formation of thermodynamically most stable product. The self-assembly of the DB24C8 ring onto the recognition site known as templating effect was driven by noncovalent stabilizing interactions like [N+–H⋯O], [C–H⋯O] hydrogen bonds as well as [π⋯π] interactions which is facilitated in non-polar solvents. The reversible nature of olefin metathesis reaction makes it suitable for dynamic covalent chemistry since proof-reading and error-checking operates until it generates thermodynamically the most stable interlocked molecule. Riding on the success of [5]molecular necklace, we went a step further and attempted to synthesize [7]molecular necklace using the same protocol. This led to the synthesis of another thread with olefin at both ends but having six dibenzylammonium ions along the thread. However, the extremely poor solubility of this thread containing six secondary ammonium ions limits the self-assembly process even after we replaced the typical PF6 counter anion with a more lipophilic BPh4 anion. Although the poor solubility of the thread remains the bottleneck for making higher order molecular necklaces yet this approach of “threading-followed-by-ring-closing-metathesis” for the first time produces kinetically and thermodynamically stable, well-defined, homogeneous molecular necklace which was well characterized by one-dimensional, two-dimensional, variable temperature proton NMR spectroscopy and ESI mass spectroscopy.

Enantioselective radical cyclisation reactions of 4-substituted quinolones mediated by a chiral template by Aline Bakowski; Martina Dressel; Andreas Bauer; Thorsten Bach (3516-3529).
Six 4-substituted quinolones 6–8, which bear an ω-iodoalkyl chain, were prepared and subjected to reductive radical cyclisation conditions employing BEt3/O2 as the initiator and either Bu3SnH or TMS3SiH as hydride source. 4-(4-Iodobutyl)-quinolone (6a) and 4-(3-iodopropylthio)-quinolone (8a) gave the respective 6-endo-cyclisation products in good yields. 4-(3,3-Dimethyl-4-iodobutyl)-quinolone (6b) cyclised in a 5-exo-fashion, while the other substrates delivered only reduction products. The cyclisation reactions could be conducted in the presence of a chiral template (1) with high enantiomeric excess (94–99% ee). The association behaviour of substrate 6a to 1 was studied by NMR titration experiments. In the enantioselective cyclisation of 6b a significant nonlinearity was observed when comparing the product ee with the ee of the template.

Synthesis and evaluation of self-calibrating ratiometric viscosity sensors by Hyung-Jo Yoon; Marianna Dakanali; Darcy Lichlyter; Willy M. Chang; Karen A. Nguyen; Matthew E. Nipper; Mark A. Haidekker; Emmanuel A. Theodorakis (3530-3540).
We describe the design, synthesis and fluorescent profile of a family of self-calibrating dyes that provide ratiometric measurements of fluid viscosity. The design is based on covalently linking a primary fluorophore (reference) that displays a viscosity-independent fluorescence emission with a secondary fluorophore (sensor) that exhibits a viscosity-sensitive fluorescence emission. Characterization of fluorescent properties was made with separate excitation of the units and through Resonance Energy Transfer from the reference to the sensor dye. The chemical structures of both fluorophores and the linker length have been evaluated in order to optimize the overall brightness and sensitivity of the viscosity measurements. We also present an application of such ratiometric dyes for the detection of membrane viscosity changes in a liposome model.

Linoleic acid peroxidation vs. isomerization: a biomimetic model of free radical reactivity in the presence of thiols by Branka Mihaljević; Ivana Tartaro; Carla Ferreri; Chryssostomos Chatgilialoglu (3541-3548).
Biomimetic models of free radical-induced transformation of polyunsaturated fatty acids, such as micelles and liposomes, have been used for the study of lipid peroxidation and lipid isomerization. Free radical reactivity of thiol compounds is the common link between the two processes, since lipid peroxidation is inhibited by thiols, due to their H-donation ability, whereas lipid isomerization is catalysed by S-centered radicals. In this paper the two processes are compared for the first time, in solution and under biomimetic conditions, demonstrating that hydroperoxides and trans lipids are formed to comparable extents as a result of oxidative free radical conditions. The biomimetic model of micelles of linoleic acid, prepared by addition of a non-ionic surfactant (TWEEN®-20) and 2-mercaptoethanol as the amphiphilic thiol, was irradiated by ionizing radiation up to 400 Gy under various conditions. In air-equilibrated solutions, the cis–trans isomerization process was observed with a catalytic cycle of 370 together with a substantial amount of hydroperoxides (LOOH). The effect of micelle size was also studied in order to envisage the effect of the supramolecular organization on the outcome of the two processes, and in particular, for the positional preference of the double bond isomerization.

Photoswitchable rotaxanes on gold nanoparticles by Yingxin Duo; Sabine Jacob; Werner Abraham (3549-3559).
We studied rotaxanes that consisted of a molecular axle, with a photoactive 9-Aryl-9-methoxy-acridane moiety at one end, and a tetracationic ring of cyclobis(paraquat-p-phenylene) (CBQT4+). The aim of the study was to deposit the axle ends onto gold nanoparticles (AuNPs). First, we introduced thioctic acid into the axle molecules. Then, rotaxanes were deposited on AuNPs by two methods: 1) Pseudorotaxanes were deposited on the gold surface by forming rotaxanes with the AuNP as a terminator to prevent unthreading of the ring structure; and 2) a chain containing the thioctic ester was introduced into a complete rotaxane, and then it was deposited on the AuNP with the aid of an exchange process. The photoheterolysis of the acridane unit resulted in formation of the corresponding acridinium methoxide; this, in turn, could thermally react to return to the acridane moiety. Due to the creation of a positive charge, the ring moved from the acridane station to a second, evasive station within the axle. This switching cycle could also take place when deposited on the gold surface. However, on the gold surface, the ring movement associated with the switching process was unidirectional.

Reactions of super-electron-donors (SEDs) derived from 4-dimethylaminopyridine and from N-methylbenzimidazole with α-methoxy-γ-alkoxyalkyl iodides lead to liberation of the γ-alkoxy groups as their alcohols. This is consistent with generation of alkyl radicals from the alkyl halide precursors, and trapping of these radicals by the radical-cation of the SED, followed by a heterolytic fragmentation.

Back cover (3571-3572).