Publications of the Department of Organic Chemistry

15. 

Nitrogen- and sulfur-based Stevens and related rearrangements.

Bach, R.; Harthong, S.; Lacour, J.

Accepted for publication in Comprehensive Organic Synthesis, 2nd ed.; Molander, G.; Knochel, P. (Eds.); Elsevier.

14. 

Structure and dynamic of three indole alkaloids from Campylospermum genus (Ochnaceae).

Bayiha Ba Njock, G.; Bartholomeusz, T. A.; Ngono Bikobo, D.; Foroozandeh, M.; Shivapurkar, R.; Christen, P.; Pegnyemb, D. E.; Jeannerat, D.

Helv. Chim. Acta, in press.

13. 

DNA as a Platform to Program Assemblies with Emerging Functions in Chemical Biology.

Sadhu, K. K.; Röthlingshöfer, M.; Winssinger, N.

Isr. J. Chem. 2013, 53, 75-86.

open archive unige:26538 full text [restricted access]

12. 

Double-Channel Photosystems with Antiparallel Redox Gradients:  Templated Stack Exchange with Porphyrins and Phthalocyanines.

Sforazzini, G.; Turdean, R.; Sakai, N.; Matile, S.

Chem. Sci., in press.

We report the synthesis of multicomponent surface architectures composed of phthalocyanines (Pc), porphyrins (TPP) and naphthalenediimides (NDI). Naphthalenediimide stacks are grown first by self-organizing surface initiated disulfide-exchange polymerization (SOSIP). An oriented redox gradient driving electrons toward the surface is applied by growing electron-richer NDI stacks on top of poorer ones. Lateral stacks of porphyrins and phthalocyanines are then added by templated stack exchange (TSE). A three-component gradient is constructed to drive the holes away from the solid surface. Antiparallel gradients are found to minimize charge recombination during photocurrent generation. Templates used for stack exchange also serve as hole barriers, whereas their size has surprisingly little importance. These results demonstrate the compatibility of SOSIP-TSE technology with porphyrins and phthalocyanines, confirm the importance of oriented antiparallel gradients to minimize charge recombination, and show that electronics rather than the size matter to template stack exchange.

11. 

3,4-Ethylenedioxythiophene in Planarizable Push-Pull Oligothiophenes.

Dal Molin, M.; Matile, S.

Org. Biomol. Chem. 2013, 11, 1952-1957.

We report design, synthesis and evaluation of push–pull quaterthiophene amphiphiles containing one 3,4-ethylenedioxythiophene (EDOT) and a single strong twist in the scaffold. Planarizable push–pull oligothiophene amphiphiles have been introduced recently as conceptually innovative fluorescent probes that sense the fluidity and the potential of lipid bilayer membranes. The “hyper-twisted” EDOT probes respond to planarization and restricted rotational freedom with a red shift and changes in vibrational finestructure in the excitation spectrum, respectively. In solution, comparably weak solvatochromism and significant thermochromism are found. Planarization and restricted rotational freedom afford exquisite sensitivity toward nature and fluidity of lipid bilayer membranes, including ratiometric detection of phase transitions. The sensing of membrane potentials is weakened by these unique properties but remains possible.

10. 

Substrate-Initiated Synthesis of Cell-Penetrating Poly(disulfide)s.

Bang, E.-K.; Gasparini, G.; Molinard, G.; Roux, A.; Sakai, N.; Matile, S.

J. Am. Chem. Soc. 2013, 135, 2088-2091.

open archive unige:26439 full text [restricted access]

Lessons from surface-initiated polymerization are applied to grow cell-penetrating poly(disulfide)s directly on substrates of free choice. Reductive depolymerization after cellular uptake should then release the native substrates and minimize toxicity. In the presence of thiolated substrates, propagators containing a strained disulfide from asparagusic or, preferably, lipoic acid and a guanidinium cation polymerize into poly(disulfide)s in less than 5 min at room temperature at pH 7. Substrate-initiated polymerization of cationic poly(disulfide)s and their depolymerization with dithiothreitol causes the appearance and disappearance of transport activity in fluorogenic vesicles. The same process is further characterized by gel-permeation chromatography and fluorescence resonance energy transfer.

9. 

Determination of Labile Chiral Supramolecular Ion Pairs by Chromatographic NMR Spectroscopy.

Reddy, G. N. M.; Ballesteros-Garrido, R.; Lacour, J.; Caldarelli, S.

Angew. Chem. Int. Ed., in press.

Silica-enhanced NMR diffusometry can distinguish the signals of diastereoisomeric mixtures of supramolecular ion pairs. The experiment has a shorter timescale than Liquid Chromatography, thus allowing an easier characterization of species that are even configurationally labile on the minutes timescale.

8. 

Copper-Catalyzed Asymmetric Conjugate Addition of Alkenyl- and Alkylalanes to α,β-Unsaturated Lactams.

Cottet, P.; Müller, D.; Alexakis, A.

Org. Lett. 2013, 15, 828-831.

open archive unige:26461 full text [restricted access]

Alkenyl and alkyl groups have been successfully introduced to six-membered α,β-unsaturated lactams via a copper-catalyzed asymmetric 1,4-addition of the corresponding alanes. Moderate to good yields and good to excellent enantioselectivities are achieved by using a combination of the very cheap copper(II) naphthenate and a readily available phosphine amine ligand. The creation of an all-carbon quaternary stereogenic center, via Michael addition to a trisubstituted conjugated lactam, is also disclosed for the first time.

7. 

Self-Organizing Surface-Initiated Polymerization, Templated Self-Sorting and Templated Stack Exchange:  Synthetic Methods to Build Complex Systems.

Lista, M.; Orentas, E.; Areephong, J.; Charbonnaz, P.; Wilson, A.; Zhao, Y.; Bolag, A.; Sforazzini, G.; Turdean, R.; Hayashi, H.; Domoto, Y.; Sobczuk, A.; Sakai, N.; Matile, S.

Org. Biomol. Chem. 2013, 11, 1754-1765.

open archive unige:26501 full text [restricted access]

In nature, spectacular function is achieved by highly sophisticated supramolecular architectures. Little is known what we would obtain if we could create complexity with similar precision, because the synthetic methods to do so are not available. This account summarizes recent approaches conceived to improve on this situation. With self-organizing surface-initiated polymerization (SOSIP), charge-transporting stacks can be grown directly on solid substrates with molecular-level precision. The extension to templated self-sorting (SOSIP-TSS) offers a supramolecular approach to multicomponent architectures. A solid theoretical framework for the transcription of information by templated self-sorting has been introduced, intrinsic templation efficiencies up to 97% have been achieved, and the existence of self-repair has been shown. The extension to templated stack exchange (SOSIP-TSE) offers the complementary covalent approach. Compatibility of this robust method with the creation of double-channel architectures with antiparallel two-component gradients has been demonstrated.

6. 

Synthesis, Structural Analysis and Catalytic Properties of Tetrakis (Binaphthyl or Octahydrobinaphthyl Phosphate) Dirhodium(II,II) Complexes.

Hrdina, R.; Guénée, L.; Moraleda, D.; Lacour, J.

Organometallics 2013, 32, 473-479.

open archive unige:26052 full text [restricted access]

The X-ray structural analyses of homoleptic Rh(II) complexes made of enantiopure (R)-1,1’-binaphthyl and (R)-(5,5’,6,6’,7,7’,8,8’-octahydro)-binaphthyl phosphate ligands are for the first time presented. The possibility to introduce halogen atoms at the 3,3’-positions is also reported. The isolated dirhodium complexes were further tested as catalysts (1 mol %) in enantioselective cyclopropanations and Si-H insertion reactions.

5. 

Modular Synthesis, Orthogonal Post-Functionalization, Absorption and Chiroptical Properties of Cationic [6]Helicenes.

Torricelli, F.; Bosson, J.; Besnard, C.; Chekini, M.; Bürgi, T.; Lacour, J.

Angew. Chem. Int. Ed. 2013, 52, 1796-1800.

open archive unige:26214 full text [restricted access]

Novel cationic diaza, azaoxo and dioxo [6]helicenes are readily prepared and functionalized selectively by orthogonal aromatic electrophilic and vicarious nucleophilic substitutions; reduction, cross-coupling or condensation reactions bringing further diversity. Absorption properties up to the near Infra-Red window are tuned thanks to these late-stage transformations. The diaza helicene can be furthermore resolved into single enantiomeric salts of known configuration.

4. 

Stereoselective Self-Sorting on Surfaces:  Transcription of Chiral Information.

Orentas, E.; Sakai, N.; Matile, S.

Chirality 2013, 25, 107-113.

open archive unige:26129 full text [restricted access]

3. 

Copper-Free Asymmetric Allylic Alkylation with a Grignard Reagent: Design of the Ligand and Mechanistic Studies.

Grassi, D.; Dolka, C.; Jackowski, O.; Alexakis, A.

Chem. Eur. J. 2013, 19, 1466-1475.

open archive unige:25800 full text [restricted access]

The Cu-free asymmetric allylic alkylation, catalysed by NHC, with Grignard reagents is reported on allyl bromide derivatives with good results. The enantioselectivity was quite homogeneous (around 85 % ee) on large and various substrates, regardless of the nature of the Grignard reagent. The formation of stereogenic quaternary centres was highly regioselective for both aliphatic and aromatic derivatives with good enantiomeric excess (up to 92 % ee). The methodology developed was found to be complementary with the Cu-catalysed version. Several new NHCs were tested with improved efficiency. In addition, mechanistic studies, using NMR spectroscopy, led to the discovery of the catalytically active species.

2. 

Self-Assembled Antibody Multimers through Peptide Nucleic Acid Conjugation.

Kazane, S. A.; Axup, J. Y.; Kim, C. H.; Ciobanu, M.; Wold, E. D.; Barluenga, S.; Hutchins, B. A.; Schultz, P. G.; Winssinger, N.; Smider, V. V.

J. Am. Chem. Soc. 2013, 135, 340-346.

open archive unige:25547 full text [restricted access]

With the recent clinical success of bispecific antibodies, a strategy to rapidly synthesize and evaluate bispecific or higher order multispecific molecules could facilitate the discovery of new therapeutic agents. Here we show that unnatural amino acids (UAAs) with orthogonal chemical reactivity can be used to generate site-specific antibody-oligonucleotide conjugates. These constructs can then be self-assembled into multimeric complexes with defined composition, valency and geometry. Using this approach, we generated potent bispecific antibodies that recruit cytotoxic T lymphocytes to Her2 and CD20 positive cancer cells, as well as multimeric antibody fragments with enhanced activity. This strategy should accelerate the synthesis and in vitro characterization of antibody constructs with unique specificities and molecular architectures.

1. 

Sensing Applications of Synthetic Transport Systems.

Takeuchi, T.; Matile, S.

Chem. Commun. 2013, 49, 19-29.

open archive unige:24311 full text [restricted access]

This feature article offers a comprehensive account of a decade of research devoted to the combination of the grand sensing principles with synthetic transport systems that act in lipid bilayers. Differential sensing, that is pattern generation and pattern recognition, is exemplified with an artificial nose. The aptamer version of immunosensing is realized with sticky-end polymers of DNA double helices for both signal generation and signal transduction. Biosensing, that is the use of enzymes for signal generation, is exemplified first with an artificial tongue and then expanded to analytes such as cholesterol, phytate or polyphenols. Enjoyable also for the general reader, we hope that this account will inspire supramolecular organic as well as analytical, physical and biological chemists.