Andre Dallmann

Control of Imine Exchange Kinetics with Photoswitches to Modulate Self‐Healing in Polysiloxane Networks by Light Illumination

Various aldehyde-containing photoswitches have been developed whose reactivity toward amines can be controlled externally. A thermally stable bifunctional diarylethene, which in its ring-closed form exhibits imine formation accelerated by one order of magnitude, was used as a photoswitchable crosslinker and mixed with a commercially available amino-functionalized polysiloxane to yield a rubbery material with viscoelastic and self-healing properties that can be reversibly tuned by irradiation.

Local THz Time Domain Spectroscopy of Duplex DNA via Fluorescence of an Embedded Probe

We demonstrate that THz vibrational activity of a biopolymer can be measured locally, on the effective length scale for polar solvation, with an embedded molecular probe. For this purpose, the polarity probe 2-hydroxy-7-nitrofluorene was linked into a 13mer DNA duplex opposite an abasic site. The NMR solution structure shows that the fluorene moiety occupies a well-defined position in place of a base pair but can flip around the long axis on a millisecond time scale. Femtosecond optical pump-probe experiments are used to measure the time-resolved Stokes shift of emission from the probe. The dynamic shifts for solution in H(2)O and D(2)O are quantified. Their difference is much larger than that expected for free water, implying that only bound water is observed. A weak 26 cm(-1) spectral oscillation of the emission band is observed, which is not present when the probe is free in solution and is therefore caused by the supramolecular structure (DNA and hydration water).

Advancing Drug Formulation Additives toward Precision Additives with Release Mediating Peptide Interlayer

Amphiphilic drug formulation additives based on palmitic acid-modified poly(ethylene glycol) (Pal-PEG) are combined with a tailored drug binding peptide that is positioned at the hydrophobic-hydrophilic interface. The peptide originates from combinatorial selection and enables precise modulation of the drug release profiles. While Pal provides a cost-effective reservoir for drug storage, the PEG realizes solubility and shielding. The precision additives reach high payloads close to 1:1, rendering a photosensitizer water-soluble and providing adjustable drug activation kinetics by fine-tuning the peptide interface layer.

Site‐Specific Isotope‐Labeling of Inosine Phosphoramidites and NMR Analysis of an Inosine‐Containing RNA Duplex

Structural features and internal dynamics of inosine-containing RNAs are poorly understood. NMR studies of such RNAs require 13 C,15 N-labeling, which cannot be achieved using in vitro transcription as inosine and guanosine are not distinguished by RNA polymerase. Herein, we report the synthesis of an inosine phosphoramidite with selective 13 C8 and 15 N7-isotope incorporation in the base and uniform 13 C-labeling of the ribose. Chemical synthesis of an RNA duplex containing four consecutive IU base pairs with this optimized isotope-labeling scheme greatly simplifies NMR spectra and resolves signal overlap. The absence of detectable NMR signals of imino protons and unusual inter-residue NOE correlations in this RNA indicate deviations from standard A-form geometry, consistent with reduced stability of this duplex seen in UV melting studies compared to its nonedited RNA counterparts. These studies indicate that the introduction of IU base pairs distorts and destabilizes RNA helices significantly compared to the also noncanonical GU base-pairs. Our optimized isotope-labeling scheme enables high-resolution NMR studies of inosine-edited RNAs.

A photoswitchable catalyst system for remote-controlled (co)polymerization in situ

The fundamental properties of a polymeric material are ultimately governed by its structure, which mainly relies on monomer composition and connection, topology, chain length, and polydispersity. Thus far, these structural characteristics are typically set ex situ by the specific polymerization procedure, eventually limiting the future design space for the creation of more sophisticated polymers. Herein, we report on a single photoswitchable catalyst system, which enables in situ remote control over the ring-opening polymerization of l-lactide and further allows regulation of the incorporation of trimethylene carbonate and δ-valerolactone monomers in copolymerizations. By implementing a phenol moiety into a diarylethene-type structure, we exploit light-induced keto–enol tautomerism to switch the hydrogen-bonding-mediated monomer activation reversibly ON and OFF. This general and versatile principle allows for exquisite external modulation of ground-state catalysis of a living polymerization process in a closed system by ultraviolet and visible light and should thereby facilitate the generation of new polymer structures.The properties of polymers depend on monomer composition and chain length, but regulating these structural features during polymer synthesis is a challenge. Now Hecht and co-workers report a photoswitchable catalyst system that can repeatedly be switched between ON and OFF states, allowing remote control of the polymerization process. Furthermore, copolymerization with control over monomer incorporation is demonstrated.

Light-driven molecular trap enables bidirectional manipulation of dynamic covalent systems

Bond formation between two molecular entities in a closed system strictly obeys the principle of microscopic reversibility and occurs in favour of the thermodynamically more stable product. Here, we demonstrate how light can bypass this fundamental limitation by driving and controlling the reversible bimolecular reaction between an N-nucleophile and a photoswitchable carbonyl electrophile. Light-driven tautomerization cycles reverse the reactivity of the C=O/C=N-electrophiles (‘umpolung’) to activate substrates and remove products, respectively, solely depending on the illumination wavelength. By applying either red or blue light, selective and nearly quantitative intermolecular bond formation/scission can be achieved, even if the underlying condensation/hydrolysis equilibrium is thermodynamically disfavoured. Exploiting light-driven in situ C=N exchange, our approach can be used to externally regulate a closed dynamic covalent system by actively and reversibly removing specific components, resembling a molecular and bidirectional version of a macroscopic Dean–Stark trap.Light can selectively drive and control the reversible reaction between a nitrogen nucleophile and a photoswitchable carbonyl electrophile by inducing wavelength-specific tautomerization cycles. This enables external and bidirectional regulation of closed dynamic covalent systems via C=N exchange, resembling a light-powered bidirectional molecular-scale Dean–Stark trap.

Features of Auxiliaries That Enable Native Chemical Ligation beyond Glycine and Cleavage via Radical Fragmentation

Native chemical ligation (NCL) is an invaluable tool in the total chemical synthesis of proteins. Ligation auxiliaries overcome the requirement for cysteine. However, the reported auxiliaries remained limited to glycine-containing ligation sites and the acidic conditions applied for cleavage of the typically applied N-benzyl-type linkages promote side reactions. With the aim to improve upon both ligation and cleavage, we systematically investigated alternative ligation scaffolds that challenge the N-benzyl dogma. The study revealed that auxiliary-mediated peptide couplings are fastest when the ligation proceeds via 5-membered rather than 6-membered rings. Substituents in α-position of the amine shall be avoided. We observed, perhaps surprisingly, that additional β-substituents accelerated the ligation conferred by the β-mercaptoethyl scaffold. We also describe a potentially general means to remove ligation auxiliaries by treatment with an aqueous solution of triscarboxyethylphosphine (TCEP) and morpholine at pH 8.5. NMR analysis of a 13 C-labeled auxiliary showed that cleavage most likely proceeds through a radical-triggered oxidative fragmentation. High ligation rates provided by β-substituted 2-mercaptoethyl scaffolds, their facile introduction as well as the mildness of the cleavage reaction are attractive features for protein synthesis beyond cysteine and glycine ligation sites.

Specific decoration of a discrete bismuth oxido cluster by selected peptides toward the design of metal tags

Metal tags find application in a multitude of biomedical systems and the combination with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) offers an opportunity for multiplexing. To lay the foundation for an increase of the signal intensities in such processes, we herein present a general approach for efficient functionalization of a well-defined metal oxido cluster [Bi6 O4 (OH)4 (SO3 CF3 )6 (CH3 CN)6 ]⋅2 CH3 CN (1), which can be realized by selecting 7mer peptide sequences via combinatorial means from large one-bead one-compound peptide libraries. Selective cluster-binding peptide sequences (CBS) for 1 were discriminated from non-binders by treatment with H2 S gas to form the reduction product Bi2 S3 , clearly visible to the naked eye. Interactions were further confirmed by NMR experiments. Extension of a binding peptide with a maleimide linker (Mal) introduces the possibility to covalently attach thiol-bearing moieties such as biological probes and for their analysis the presence of the cluster instead of mononuclear entities should lead to an increase of signal intensities in LA-ICP-MS measurements. To prove this, CBS-Mal was covalently bound onto thiol-presenting glass substrates, which then captured 1 effectively, so that LA-ICP-MS measurements demonstrated drastic signal amplification compared to single lanthanide tags.