Jan Steinkoenig

Ugi multicomponent reaction to prepare peptide–peptoid hybrid structures with diverse chemical functionalities

Monodisperse sequenced peptides and peptoids present unique nano-structures based on their self-assembled secondary and tertiary structures. However, the generation of peptide and peptoid hybrid oligomers in a sequence-defined manner via Ugi multicomponent reaction has not yet been studied. Herein, we report a synthetic strategy that enables both the modification of peptides as well as the generation of sequence-defined peptide–peptoid hybrid structures. Our synthetic methodology rests on the fusion of solid phase peptide synthesis with Ugi multicomponent reactions. We evidence that a diversity of chemical functionalities can be inserted into peptides or used in the design of peptide–peptoid hybrids exploiting a wide functional array including amines, carboxylic acids, hydrocarbons, carbohydrates as well as polymers, introducing a sequence-defined synthetic platform technology for precision peptoid hybrids.

Oxidative polymerization of catecholamines: structural access by high-resolution mass spectrometry

We introduce the high-resolution electrospray ionization mass spectrometric (ESI MS) structural elucidation of polymerized 3,4-dihydroxy-L-phenylalanine (L-DOPA) carrying 1-methoxy-2,2,6,6-tetramethylpiperidin-4-amide groups in the side chain. Critically, our powerful ESI MS platform unambiguously revealed the structurally diverse character of this multifunctional bio-adhesive polymer system.

Imaging Single-Chain Nanoparticle Folding via High-Resolution Mass Spectrometry

Herein, we introduce the first approach to map single-chain nanoparticle (SCNP) folding via high-resolution electrospray ionization mass spectrometry (ESI MS) coupled with size exclusion chromatography. For the first time, the successful collapse of polymeric chains into SCNPs is imaged by characteristic mass changes, providing detailed mechanistic information regarding the folding mechanism. As SCNP system we employed methyl methacrylate (MMA) statistically copolymerized with glycidyl methacrylate (GMA), resulting in p(MMA-stat-GMA), subsequently collapsed by using B(C6F5)3 as catalyst. Both the precursor polymer and the SCNPs can be well ionized via ESI MS, and the strong covalent cross-links are stable during ionization. Our high-resolution mass spectrometric approach can unambiguously differentiate between two mechanistic modes of chain collapse for every chain constituting the SCNP sample.

High resolution mass spectrometric access to nitroxide containing polymers

We introduce a mass spectrometric access route to nitroxide containing polymers via high resolution electrospray ionization mass spectrometry (HR ESI MS), a polymer class that is – due to the presence of unpaired spins – highly challenging to analyze via NMR techniques. The nitroxide content within the polymer chain structure was varied between 11.3 and 29.1 mol% in a statistical copolymer consisting of styrene-stat-4-(chloromethyl)styrene (p(S-stat-CMS), 4800 ≥ Mn/g mol−1 ≥ 11 100), where 4-carboxy-2,2,6,6-tetramethylpiperidine 1-oxyl (4-carboxy-TEMPO) units were attached by post-polymerization modification. By carefully evaluating the isotopic pattern of the nitroxide containing polymers, we demonstrate that the persistent nitroxyl radical retains its structural integrity during the soft ionization process employing spray currents up to 4.3 keV and in-source collision induced dissociation energies up to 30 eV using chloride attachment technology in negative ion mode. Interestingly, high-molecular weight gas-phase aggregates are identified with increasing amounts of nitroxide side-chain functionalization. To further exemplify the power of the introduced mass spectrometric protocol, a well-defined styrene based polymer was synthesized via atom transfer radical polymerization (ATRP, Mn = 5600 g mol−1, Đ = 1.05) containing functional groups, i.e. a terminal cyanuric acid unit and Hamilton Wedge moiety as well as a free nitroxide in the penultimate position to the Hamilton wedge. The intact persistent nitroxide radical at the chain end was unambiguously identified by its isotopic pattern in a highly defined polymer structure.

Just Add Salt: A Mass Spectrometric Analysis Method for Imaging Anion-Exchanged Poly(Ionic Liquid)s.

We report the first mass spectrometric analysis of poly(ionic liquid)s (PILs) containing weakly coordinating anions introduced by a fast, simple, and quantitative postmodification method on the example of the hydrophilic, well-defined poly(vinylbenzylpyridinium chloride) p([VBPy]Cl) species, analyzed with an in-source collision induced dissociation-Orbitrap mass spectrometry (MS) protocol. Using the MS approach allows for the precise structural elucidation of ion-exchanged p([VBPy]Cl) utilizing AgX (X = NO3- , CF3 CO2- , BF4- ) salts. The anion exchange is shown to be quantitative - without observing residual chlorinated PIL - on rapid time scales, using only filtration as a standard procedure during sample preparation. In addition, the influence of weakly coordinating anions on the ionization behavior of PILs is studied in detail.

Installing lactone chain termini during photoinduced polymerization

We exploit the Thorpe–Ingold effect as a spontaneous end group transformation method during photo-induced polymerization of methacrylates using the functional (2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone) species as radical photoinitiator. Herein, the isopropyl hydroxyl function endows the polymer with geminal methyl groups inducing an angular compression, enabling through close proximity a ring-closing reaction between the hydroxyl group and the ester motif.

Engineering Nitroxide Functional Surfaces Using Bioinspired Adhesion

We pioneer a versatile surface modification strategy based on mussel-inspired oxidative catecholamine polymerization for the design of nitroxide-containing thin polymer films. A 3,4-dihydroxy-l-phenylalanine (l-DOPA) monomer equipped with a 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-derived oxidation-labile hydroxylamine functional group is employed as a universal coating agent to generate polymer scaffolds with persistent radical character. Various types of materials including silicon, titanium, ceramic alumina, and inert poly(tetrafluoroethylene) (PTFE) were successfully coated with poly(DOPA-TEMPO) thin films in a one-step dip-coating procedure under aerobic, slightly alkaline (pH 8.5) conditions. Steadily growing polymer films (∼1.1 nm h-1) were monitored by ellipsometry, and their thicknesses were critically compared with those obtained from atomic force microscopic cross-sectional profiles. The heterogeneous composition of surface-adherent nitroxide scaffolds examined by X-ray photoelectron spectroscopy was correlated to that examined by in-solution polymer analysis via high-resolution electrospray ionization mass spectrometry, revealing oligomeric structures with up to six repeating units, mainly composed of covalently linked dihydroxyindole along the polymer backbone. Critically, the reversible redox-active character of the nitroxide-containing polymer scaffolds was investigated by cyclic voltammetric measurements, revealing a convenient and facile access route to electrochemically active nitroxide polymer coatings with potential application in electronic devices such as organic radical batteries.