Abdelaziz Al Ouahabi

Orthogonal Synthesis of “Easy-to-Read” Information-Containing Polymers Using Phosphoramidite and Radical Coupling Steps

A new orthogonal solid-phase iterative strategy is proposed for the synthesis of sequence-coded polymers. This approach relies on the use of two successive chemoselective steps: (i) phosphoramidite coupling, and (ii) radical-radical coupling. These repeated steps can be performed using two different types of building blocks, i.e. a phosphoramidite monomer that also contains an alkyl bromide and a hydroxy-functionalized nitroxide. The phosphoramidite and the hydroxy group are reacted in step (i), thus leading to a phosphite that is oxidized in situ into a phosphate bond. The alkyl bromide is activated by copper bromide in step (ii) to afford a carbon-centered radical that is spin-trapped in situ by the nitroxide. The iterative repetition of these steps allow synthesis of uniform polymers, as evidenced by high-resolution electrospray mass spectrometry. Moreover, binary information could be easily implemented in the polymers using different types of phosphoramidite monomers in step (i). Interestingly, it was found that the formed information-containing polymers are very easy to sequence by tandem mass spectrometry due to the presence of easily cleavable alkoxyamine bonds formed in step (ii).

A Simple Post‐Polymerization Modification Method for Controlling Side‐Chain Information in Digital Polymers

A three-step post-polymerization modification method was developed for the design of digitally encoded poly(phosphodiester)s with controllable side groups. Sequence-defined precursors were synthesized, either manually on polystyrene resins or automatically on controlled pore glass supports, using two phosphoramidite monomers containing either terminal alkynes or triisopropylsilyl (TIPS) protected alkyne side groups. Afterwards, these polymers were modified by stepwise copper-catalyzed azide-alkyne cycloaddition (CuAAC). The terminal alkynes were first reacted with a model azide compound, and after removal of the TIPS groups, the remaining alkynes were reacted with another organic azide. This simple method allows for quantitative side-chain modification, thus opening up interesting avenues for the preparation of a wide variety of digital polymers.

Synthesis and Properties of Oligo[n]cruciforms: Nanosized Sterically Encumbered Tetraethynylphenyl-Homologated Fluorophores

A series of nanosized phenyleneethynylenes have been prepared which are sterically insulated from the surrounding environment by multiple functionalization with triisopropylsilyl (TIPS) substituents. The phenyleneethynylenes comprise oligo[n]cruciforms 1-4 (n = 3-5) and a dehydrotribenzo[12]annulene 5, the former of which possess para-acyclic and the latter ortho-cyclic electronic conjugation pathways. All compounds were characterized by (1)H and (13)C NMR, IR, and mass spectroscopic techniques. The X-ray crystal structure of 1 confirmed the sterically isolating properties of the TIPS substituents. A comparison of the physical properties of these electronically differing systems revealed that they were all luminescent upon UV irradiation displayed negligible aggregation in dilute solution and that particular members of the series studied were electrochemically active, undergoing facile reversible reductions. The phenyleneethynylenes also exhibited significantly enhanced thermal stability by virtue of the presence of the TIPS substituents. The properties of 1-5 suggest that they are promising building blocks for the construction of materials for novel molecular electronics applications.

Mass spectrometry sequencing of long digital polymers facilitated by programmed inter-byte fragmentation

In the context of data storage miniaturization, it was recently shown that digital information can be stored in the monomer sequences of non-natural macromolecules. However, the sequencing of such digital polymers is currently limited to short chains. Here, we report that intact multi-byte digital polymers can be sequenced in a moderate resolution mass spectrometer and that full sequence coverage can be attained without requiring pre-analysis digestion or the help of sequence databases. In order to do so, the polymers are designed to undergo controlled fragmentations in collision-induced dissociation conditions. Each byte of the sequence is labeled by an identification tag and a weak alkoxyamine group is placed between 2 bytes. As a consequence of this design, the NO-C bonds break first upon collisional activation, thus leading to a pattern of mass tag-shifted intact bytes. Afterwards, each byte is individually sequenced in pseudo-MS3 conditions and the whole sequence is found.Digital information can be stored in monomer sequences of non-natural macromolecules, but only short chains can be read. Here the authors show long multi-byte digital polymers sequenced in a moderate resolution mass spectrometer. Full sequence coverage can be attained without pre-analysis digestion or the help from sequence databases.

Electronic, spectroscopic, and ion-sensing properties of a dehydro[m]pyrido[14]- and [15]annulene isomer library.

An isomeric series of dehydro[m]pyrido[n]annulenes incorporating strained 1,4-buta-1,3-diyne units have been synthesized, where m = 2, n = 14 (1a-d); m = 2, n = 15 (2a,b); and m = 3, n = 15 (3). The number of pyridine rings and annulene ring π-electrons are denoted by m and n, respectively. The X-ray crystal structures of 1b and 1c confirmed their cyclic formulation. All macrocycles were found to be luminescent chromophores with differing isomer-dependent proton and metal ion-sensory emission responses, which appear collectively as analyte-specific color patterns. Within the series studied, 1a was singular in displaying the highest luminescence quantum yield and sharing the strongest emission energy and molar absorption changes upon protonation and Hg(II) binding. Spectroscopic and electrochemical results were supported by density functional theory calculations in showing 1a, 2a, and 3 to be low bandgap materials with lowest unoccupied molecular orbitals delocalized over the 1,4-di(pyridin-4-yl)buta-1,3-diyne bridges that provide a pathway for electronic communication between the nitrogens. Overall, the investigations suggest that 1a, 2a, and 3 would be excellent ligands for the construction of novel conjugated hybrid metallosupramolecular nanostructures, polymers, and ion-sensory systems.

Optimal ATRP-Made Soluble Polymer Supports for Phosphoramidite Chemistry.

Soluble polystyrene supports with optimal molecular structures for iterative phosphoramidite chemistry were prepared by atom-transfer radical polymerization (ATRP) and subsequent chain-end modification steps. The controlled radical polymerization of styrene was first performed in the presence of an 9-fluorenylmethoxycarbonyl (Fmoc)-protected amino-functional ATRP initiator. Soluble supports of different molecular weight were prepared. Size-exclusion chromatography and NMR analysis indicated formation of well-defined polymers with controlled chain lengths and narrow dispersity. After synthesis, the bromo ω end group of the ATRP polymer was removed by dehalogenation in the presence of tributyltin hydride, and the Fmoc protecting group of the α moiety was subsequently cleaved with piperidine. The resulting α-primary amine was afterwards treated with a linker containing a carboxyl group, a cleavable ester site, and a dimethoxytrityl-protected hydroxyl group to afford ideal soluble supports for phosphoramidite chemistry. NMR analysis indicated that these chain-end modifications were quantitative. The supports were tested for the synthesis of a non-natural sequence-defined oligophosphates. High-resolution ESI-MS analysis of the cleaved oligomers indicated formation of uniform species, and thus confirmed the efficiency of the ATRP-made soluble polymer supports. In addition, the synthesis of a thymidine-loaded soluble support was achieved.

Design of Nanohybrid Systems from a Partially Fluorinated Organogelator and Syndiotactic Polystyrene Thermoreversible Gel.

Nanohybrid systems are prepared from organogels of a partially fluorinated molecule and from thermoreversible gels of syndiotactic polystyrene. The thermodynamic behavior, morphology, and structure are investigated by using differential scanning calorimetry, atomic force microscopy, small-angle X-ray scattering (SAXS), and small-angle neutron scattering (SANS). The outcomes of these investigations suggest that the fibrils of the organogel coil around the sPS fibrils, probably through a heterogeneous nucleation process. These systems therefore differ from previously investigated sPS/OPV systems (oligo vinylene phenylene) where OPV fibrils pervade the sPS network.

Origin of Invariant Gel Melting Temperatures in the c-T Phase Diagram of an Organogel.

Binary c-T phase diagrams of organogelators in solvent are frequently simplified to two domains, gel and sol, even when the melting temperatures display two distinct regimes, an increase with T and a plateau. Herein, the c-T phase diagram of an organogelator in solvent is elucidated by rheology, DSC, optical microscopy, and transmitted light intensity measurements. We evidence a miscibility gap between the organogelator and the solvent above a threshold concentration, cL. In this domain the melting or the formation of the gel becomes a monotectic transformation, which explains why the corresponding temperatures are nonvariant above cL. As shown by further studies by variable temperature FTIR and NMR, different types of H-bonds drive both the liquid-liquid phase separation and the gelation.

Experimental and theoretical study of the n-doped successive polyanions of oligocruciform molecular wires: up to five units of charge.

The electronic structure of polyanions of sterically encumbered triisopropylsilyl-substituted linear and cyclic oligo(phenyleneethynylene)s (Monomer, Trimer, Pentamer, and Triangle) is investigated by electron paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR), and UV/Vis-near-infrared (NIR) spectroscopies, cyclic voltammetry, and theoretical calculations (DFT). Increasing anion orders are generated sequentially in vacuo at room temperature by chemical reaction with potassium metal up to the pentaanion. The relevance of these compounds acting as electron reservoirs is thus demonstrated. Even-order anions are EPR silent, whereas the odd species exhibit different signatures, which are identified after comparison of the measured hyperfine couplings by ENDOR spectroscopy with those predicted by DFT calculations. With increasing size of the oligomers the electron spin density is first distributed over the backbone carbon atoms for the monoanions, and then further localized at the outer phenyl rings for the trianion species. Examination of the UV/Vis-NIR spectra indicates that the monoanions (T(.-) , P(.-) ) exhibit two transitions in the Vis-NIR region, whereas a strong absorption in the IR region is solely observed for higher reduced states. Electronic transitions of the neutral monoanions and trianions are redshifted with increasing oligomer size, whereas for a given oligomer a blueshift is observed upon increasing the charge, which suggests a localization of the spin density.

Translocation of Precision Polymers through Biological Nanopores

Nanopore analysis, which is, currently, chiefly used for DNA sequencing, is also an appealing technique for characterizing abiotic polymers. As a first step toward this goal, nanopore detection of non-natural monodispersed poly(phosphodiester)s as candidate backbone structures is reported herein. Two model homopolymers containing phosphopropyl repeat units (i.e., 56 or 104 r.u.) and a short thymidine nucleotide sequence are analyzed in the present work. They are tested in two different biological nanopores, α-hemolysin from Staphylococcus aureus, and aerolysin from Aeromonas hydrophila. These recordings are performed in aqueous medium at different KCl concentrations and various driving voltages. The data show a complex interaction with evidence for voltage dependence and threading, and underline the influence of the molecular structure and orientation of the precision poly(phosphodiester)s on the observed residual current signal as well as on the translocation dynamics. In particular, they suggest a dominant entropic contribution due to the high flexibility of the phosphodiester homopolymer.