Alexander Schiller

Red Light-Triggered CO Release from Mn2(CO)10 Using Triplet Sensitization in Polymer Nonwoven Fabrics

Co-reporter:Sven H. C. Askes, G. Upendar Reddy, Ralf Wyrwa, Sylvestre Bonnet, and Alexander Schiller

Journal of the American Chemical Society November 1, 2017 Volume 139(Issue 43) pp:15292-15292

Publication Date(Web):October 3, 2017

DOI:10.1021/jacs.7b07427

Applicability of phototherapeutic CO-releasing molecules (photoCORMs) is limited because they are activated by harmful and poorly tissue-penetrating near-ultraviolet light. Here, a strategy is demonstrated to activate classical photoCORM Mn2(CO)10 using red light (635 nm). By mixing in solution a triplet photosensitizer (PS) with the photoCORM and shining red light, energy transfer occurs from triplet excited-state 3PS* to a photolabile triplet state of Mn2(CO)10, which, like under near-UV irradiation, led to complete release of carbonyls. Crucially, such “triplet-sensitized CO-release” occurred in solid-state materials: when PS and Mn2(CO)10 were embedded in electrospun nonwoven fabrics, CO was liberated upon irradiation with low-intensity red light (≤36 mW 635 nm).

Fluorinated Boronic Acid-Appended Pyridinium Salts and 19F NMR Spectroscopy for Diol Sensing

Co-reporter:Jörg Axthelm, Sven H. C. Askes, Martin Elstner, Upendar Reddy G, Helmar Görls, Peter Bellstedt, and Alexander Schiller

Journal of the American Chemical Society August 23, 2017 Volume 139(Issue 33) pp:11413-11413

Publication Date(Web):July 18, 2017

DOI:10.1021/jacs.7b01167

The identification and discrimination of diols is of fundamental importance in medical diagnostics, such as measuring the contents of glucose in the urine of diabetes patients. Diol sensors are often based on fluorophore-appended boronic acids, but these severely lack discriminatory power and their response is one-dimensional. As an alternative strategy, we present the use of fluorinated boronic acid-appended pyridinium salts in combination with 19F NMR spectroscopy. A pool of 59 (bio)analytes was screened, containing monosaccharides, phosphorylated and N-acetylated sugars, polyols, carboxylic acids, nucleotides, and amines. The majority of analytes could be clearly detected and discriminated. In addition, glucose and fructose could be distinguished up to 1:9 molar ratio in mixtures. Crucially, the receptors feature high sensitivity and selectivity and are water-soluble, and their 19F-NMR analyte fingerprint is pH-robust, thereby making them particularly well-suited for medical application. Finally, to demonstrate this applicability, glucose could be detected in synthetic urine samples down to 1 mM using merely a 188 MHz NMR spectrometer.

Light-responsive paper strips as CO-releasing material with a colourimetric response

Co-reporter:Upendar Reddy G.;Jingjing Liu;Patrick Hoffmann;Johannes Steinmetzer;Helmar Görls;Stephan Kupfer;Sven H. C. Askes;Ute Neugebauer;Stefanie Gräfe

Chemical Science (2010-Present) 2017 vol. 8(Issue 9) pp:6555-6560

Publication Date(Web):2017/08/21

DOI:10.1039/C7SC01692A

Carbon monoxide (CO) is known for its multifaceted role in human physiology, and molecules that release CO in a controlled way have been proposed as therapeutic drugs. In this work, a light-responsive CO-releasing molecule (CORM-Dabsyl) showed a strong colourimetric response upon photochemical CO-release, owing to the tight conjugation of a Mn(I) tricarbonyl centre to a dabsyl chromophoric ligand (L). Whereas the complex was very stable in the dark in nitrogen-purged aqueous media, CO-release was effectively triggered using 405 nm irradiation. CORM-Dabsyl, L and the inactive product iCORM-Dabsyl have been investigated by DFT and TD-DFT calculations. Only mild toxicity of CORM-Dabsyl was observed against LX-2 and HepaRG® human cell lines (IC50 ∼ 30 μM). Finally, to develop a CO storage and release material that is readily applicable to therapeutic situations, CORM-Dabsyl was loaded on low-cost and easily disposable paper strips, from which the light triggered CO-release was conveniently visible with the naked eye.

Remote-controlled delivery of CO via photoactive CO-releasing materials on a fiber optical device

Co-reporter:Steve Gläser, Ralf Mede, Helmar Görls, Susanne Seupel, Carmen Bohlender, Ralf Wyrwa, Sina Schirmer, Sebastian Dochow, Gandra Upendar Reddy, Jürgen Popp, Matthias Westerhausen and Alexander Schiller

Dalton Transactions 2016 vol. 45(Issue 33) pp:13222-13233

Publication Date(Web):08 Jul 2016

DOI:10.1039/C6DT02011A

Although carbon monoxide (CO) delivery materials (CORMAs) have been generated, remote-controlled delivery with light-activated CORMAs at a local site has not been achieved. In this work, a fiber optic-based CO delivery system is described in which the photoactive and water insoluble CO releasing molecule (CORM) manganese(I) tricarbonyl [(OC)3Mn(μ3-SR)]4 (R = nPr, 1) has been non-covalently embedded into poly(L-lactide-co-D/L-lactide) and poly(methyl methacrylate) non-woven fabrics via the electrospinning technique. SEM images of the hybrid materials show a porous fiber morphology for both polymer supports. The polylactide non-woven fabric was attached to a fiber optical device. In combination with a laser irradiation source, remote-controlled and light-triggered CO release at 405 nm excitation wavelength was achieved. The device enabled a high flexibility of the spatially and timely defined application of CO with the biocompatible hybrid fabric in aqueous media. The rates of liberated CO were adjusted with the light intensity of the laser. CO release was confirmed via ATR-IR spectroscopy, a portable electrochemical CO sensor and a heterogeneous myoglobin assay.

Fluorinated Boronic Acid-Appended Bipyridinium Salts for Diol Recognition and Discrimination via 19F NMR Barcodes

Co-reporter:Jörg Axthelm; Helmar Görls; Ulrich S. Schubert

Journal of the American Chemical Society 2015 Volume 137(Issue 49) pp:15402-15405

Publication Date(Web):November 23, 2015

DOI:10.1021/jacs.5b10934

Fluorinated boronic acid-appended benzyl bipyridinium salts, derived from 4,4′-, 3,4′-, and 3,3′-bipyridines, were synthesized and used to detect and differentiate diol-containing analytes at physiological conditions via 19F NMR spectroscopy. An array of three water-soluble boronic acid receptors in combination with 19F NMR spectroscopy discriminates nine diol-containing bioanalytes—catechol, dopamine, fructose, glucose, glucose-1-phosphate, glucose-6-phosphate, galactose, lactose, and sucrose—at low mM concentrations. Characteristic 19F NMR fingerprints are interpreted as two-dimensional barcodes without the need of multivariate analysis techniques.

Playing Tic-Tac-Toe with a Sugar-Based Molecular Computer

Co-reporter:M. Elstner;A. Schiller

Journal of Chemical Information and Modeling 2015 Volume 55(Issue 8) pp:1547-1551

Publication Date(Web):July 23, 2015

DOI:10.1021/acs.jcim.5b00324

Today, molecules can perform Boolean operations and circuits at a level of higher complexity. However, concatenation of logic gates and inhomogeneous inputs and outputs are still challenging tasks. Novel approaches for logic gate integration are possible when chemical programming and software programming are combined. Here it is shown that a molecular finite automaton based on the concatenated implication function (IMP) of a fluorescent two-component sugar probe via a wiring algorithm is able to play tic-tac-toe.

Sensitization of NO-Releasing Ruthenium Complexes to Visible Light

Co-reporter:Tobias Becker;Dr. Stephan Kupfer;Martin Wolfram;Dr. Helmar Görls;Dr. Ulrich S. Schubert;Dr. Eric V. Anslyn;Dr. Benjamin Dietzek;Dr. Stefanie Gräfe;Dr. Alexer Schiller

Chemistry - A European Journal 2015 Volume 21( Issue 44) pp:15554-15563

Publication Date(Web):

DOI:10.1002/chem.201502091

Abstract

We report a combined spectroscopical–theoretical investigation on the photosensitization of transition metal nitrosyl complexes. For this purpose, ruthenium nitrosyl complexes based on tetradentate biscarboxamide ligands were synthesized. A crystal structure analysis of a lithium-based ligand intermediate is described. The Ru complexes have been characterized regarding their photophysical and nitric oxide (NO) releasing properties. Quantum chemical calculations have been performed to unravel the influence of the biscarboxamide ligand frame with respect to the molecular electronic properties of the NO-releasing pathway. A quantitative measure for the ligand design within photosensitized Ru complexes is introduced and evaluated spectroscopically and theoretically by using time-dependent density functional theory.

Frontispiece: Sensitization of NO-Releasing Ruthenium Complexes to Visible Light

Co-reporter:Tobias Becker;Dr. Stephan Kupfer;Martin Wolfram;Dr. Helmar Görls;Dr. Ulrich S. Schubert;Dr. Eric V. Anslyn;Dr. Benjamin Dietzek;Dr. Stefanie Gräfe;Dr. Alexer Schiller

Chemistry - A European Journal 2015 Volume 21( Issue 44) pp:

Publication Date(Web):

DOI:10.1002/chem.201584462

Light-triggered CO release from nanoporous non-wovens

Co-reporter:Carmen Bohlender, Steve Gläser, Moritz Klein, Jürgen Weisser, Susanne Thein, Ute Neugebauer, Jürgen Popp, Ralf Wyrwa and Alexander Schiller

Journal of Materials Chemistry A 2014 vol. 2(Issue 11) pp:1454-1463

Publication Date(Web):11 Feb 2014

DOI:10.1039/C3TB21649G

The water insoluble and photoactive CO releasing molecule dimanganese decacarbonyl (CORM-1) has been non-covalently embedded into poly(L-lactide-co-D/L-lactide) fibers via electrospinning to enable bioavailability and water accessibility of CORM-1. SEM images of the resulting hybrid non-wovens reveal a nanoporous fiber morphology. Slight CO release from the CORM-1 in the electrospinning process induces nanoporosity. IR spectra show the same set of carbonyl bands for the CORM-1 precursor and the non-woven. When the material was exposed to light (365–480 nm), CO release from the incorporated CORM-1 was measured via heterogeneous myoglobin assay, a portable CO electrode and an IR gas cuvette. The CO release rate was wavelength dependent. Irradiation at 365 nm resulted in four times faster release than at 480 nm. 3.4 μmol of CO per mg non-woven can be generated. Mouse fibroblast 3T3 cells were used to show that the hybrid material is non-toxic in the darkness and strongly photocytotoxic when light is applied.

Carbon monoxide – physiology, detection and controlled release

Co-reporter:Stefan H. Heinemann, Toshinori Hoshi, Matthias Westerhausen and Alexander Schiller

Chemical Communications 2014 vol. 50(Issue 28) pp:3644-3660

Publication Date(Web):21 Feb 2014

DOI:10.1039/C3CC49196J

Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed.

Sugar-based Molecular Computing by Material Implication

Co-reporter:Martin Elstner;Jörg Axthelm ;Dr. Alexer Schiller

Angewandte Chemie International Edition 2014 Volume 53( Issue 28) pp:7339-7343

Publication Date(Web):

DOI:10.1002/anie.201403769

Abstract

A method to integrate an (in principle) unlimited number of molecular logic gates to construct complex circuits is presented. Logic circuits, such as half- or full-adders, can be reinterpreted by using the functional completeness of the implication function (IMP) and the trivial FALSE operation. The molecular gate IMP is represented by a fluorescent boronic acid sugar probe. An external wiring algorithm translates the fluorescent output from one gate into a chemical input for the next gate on microtiter plates. This process is demonstrated on a four-bit full adder.

Back Cover: Sugar-based Molecular Computing by Material Implication (Angew. Chem. Int. Ed. 28/2014)

Co-reporter:Martin Elstner;Jörg Axthelm ;Dr. Alexer Schiller

Angewandte Chemie International Edition 2014 Volume 53( Issue 28) pp:

Publication Date(Web):

DOI:10.1002/anie.201405137

Zuckerbasierter molekularer Rechner mit Implikationslogik

Co-reporter:Martin Elstner;Jörg Axthelm ;Dr. Alexer Schiller

Angewandte Chemie 2014 Volume 126( Issue 28) pp:7467-7471

Publication Date(Web):

DOI:10.1002/ange.201403769

Abstract

Ein Protokoll zur Integration einer (prinzipiell) unbeschränkten Zahl molekularer Logikgatter zum Aufbau komplexer Logikschaltungen wird präsentiert. Schaltungen, wie beispielsweise der Halb- oder Volladdierer, können unter Ausnutzung der logischen Vollständigkeit der Implikationsfunktion (IMP) und der trivialen Nullfunktion reinterpretiert werden. Das molekulare IMP-Gatter wird durch einen boronsäurehaltigen Zuckersensor beschrieben. Ein externer Verknüpfungsalgorithmus überträgt das Fluoreszenz-Ausgabesignal eines Gatters in chemische Eingaben für das nächste Gatter. Dies wird exemplarisch mit einem 4-Bit-Addierer auf der Basis von Mikrotiterplatten demonstriert.

Rcktitelbild: Zuckerbasierter molekularer Rechner mit Implikationslogik (Angew. Chem. 28/2014)

Co-reporter:Martin Elstner;Jörg Axthelm ;Dr. Alexer Schiller

Angewandte Chemie 2014 Volume 126( Issue 28) pp:

Publication Date(Web):

DOI:10.1002/ange.201405137

Allosteric Indicator Displacement Enzyme Assay for a Cyanogenic Glycoside

Co-reporter:Dr. D. Amilan Jose;Dipl.Chem. Martin Elstner;Dr. Alexer Schiller

Chemistry - A European Journal 2013 Volume 19( Issue 43) pp:14451-14457

Publication Date(Web):

DOI:10.1002/chem.201302801

Abstract

Indicator displacement assays (IDAs) represent an elegant approach in supramolecular analytical chemistry. Herein, we report a chemical biosensor for the selective detection of the cyanogenic glycoside amygdalin in aqueous solution. The hybrid sensor consists of the enzyme β-glucosidase and a boronic acid appended viologen together with a fluorescent reporter dye. β-Glucosidase degrades the cyanogenic glycoside amygdalin into hydrogen cyanide, glucose, and benzaldehyde. Only the released cyanide binds at the allosteric site of the receptor (boronic acid) thereby inducing changes in the affinity of a formerly bound fluorescent indicator dye at the other side of the receptor. Thus, the sensing probe performs as allosteric indicator displacement assay (AIDA) for cyanide in water. Interference studies with inorganic anions and glucose revealed that cyanide is solely responsible for the change in the fluorescent signal. DFT calculations on a model compound revealed a 1:1 binding ratio of the boronic acid and cyanide ion. The fluorescent enzyme assay for β-glucosidase uses amygdalin as natural substrate and allows measuring Michaelis–Menten kinetics in microtiter plates. The allosteric indicator displacement assay (AIDA) probe can also be used to detect cyanide traces in commercial amygdalin samples.

Inside Cover: Allosteric Indicator Displacement Enzyme Assay for a Cyanogenic Glycoside (Chem. Eur. J. 43/2013)

Co-reporter:Dr. D. Amilan Jose;Dipl.Chem. Martin Elstner;Dr. Alexer Schiller

Chemistry - A European Journal 2013 Volume 19( Issue 43) pp:

Publication Date(Web):

DOI:10.1002/chem.201390170

Molecular Logic with a Saccharide Probe on the Few-Molecules Level

Co-reporter:Martin Elstner ; Klaus Weisshart ; Klaus Müllen

Journal of the American Chemical Society 2012 Volume 134(Issue 19) pp:8098-8100

Publication Date(Web):April 27, 2012

DOI:10.1021/ja303214r

In this Communication we describe a two-component saccharide probe with logic capability. The combination of a boronic acid-appended viologen and perylene diimide was able to perform a complementary implication/not implication logic function. Fluorescence quenching and recovery with fructose was analyzed with fluorescence correlation spectroscopy on the level of a few molecules of the reporting dye.

Light-triggered NO release from a nanofibrous non-woven

Co-reporter:Carmen Bohlender, Martin Wolfram, Helmar Goerls, Wolfgang Imhof, Roberto Menzel, Anja Baumgaertel, Ulrich S. Schubert, Ulrike Mueller, Martina Frigge, Matthias Schnabelrauch, Ralf Wyrwa and Alexander Schiller

Journal of Materials Chemistry A 2012 vol. 22(Issue 18) pp:8785-8792

Publication Date(Web):08 Mar 2012

DOI:10.1039/C2JM15410B

Light-controlled NO delivery systems promise new applications in phototherapies. For this purpose, a ruthenium nitrosyl complex [(2)Ru(NO)(Cl)] with the novel ligand N,N′-(1,2-phenylene)bis(1-methyl-1H-imidazole-2-carboxamide) (2) has been synthesised and characterised in detail. The photoactive {Ru–NO}6 nitrosyl released NO in DMSO upon exposure to low-intensity UV-A light (λ = 366 nm). In order to create an applicable system the water-insoluble [(2)Ru(NO)(Cl)] was embedded into poly(L-lactide-co-D/L-lactide) nanofibrous non-wovens by electrospinning. Exposure of a 25 wt% non-woven of [(2)Ru(NO)(Cl)] to UV-A light resulted in a continuous release of NO into an aqueous solution. The cytoxicity of the non-woven against 3T3 mouse fibroblasts was very low.

Enzymatic Glycosylation of Small Molecules: Challenging Substrates Require Tailored Catalysts

Co-reporter: Tom Desmet; Wim Soetaert;Dr. Pavla Bojarová; Vladimir K&x159;en; Lubbert Dijkhuizen;Dr. Vanessa Eastwick-Field; Alexer Schiller

Chemistry - A European Journal 2012 Volume 18( Issue 35) pp:10786-10801

Publication Date(Web):

DOI:10.1002/chem.201103069

Abstract

Glycosylation can significantly improve the physicochemical and biological properties of small molecules like vitamins, antibiotics, flavors, and fragrances. The chemical synthesis of glycosides is, however, far from trivial and involves multistep routes that generate lots of waste. In this review, biocatalytic alternatives are presented that offer both stricter specificities and higher yields. The advantages and disadvantages of different enzyme classes are discussed and illustrated with a number of recent examples. Progress in the field of enzyme engineering and screening are expected to result in new applications of biocatalytic glycosylation reactions in various industrial sectors.

Multiwell plates loaded with fluorescent hydrogel sensors for measuring pH and glucose concentration

Co-reporter:Boaz Vilozny, Alexander Schiller, Ritchie A. Wessling and Bakthan Singaram

Journal of Materials Chemistry A 2011 vol. 21(Issue 21) pp:7589-7595

Publication Date(Web):21 Mar 2011

DOI:10.1039/C0JM04257A

Fluorescent hydrogels were polymerized directly in multi-well plates at ambient temperature and in the presence of air, producing sensors for measuring pH and glucose concentration. The plates were rapidly analyzed using a fluorescence plate reader. Multiwell pH sensors with good reproducibility among different wells and a dynamic range from pH 6 to 9 were prepared by incorporating a polymerizable pH sensitive fluorophore in the hydrogel. Non-enzymatic glucose sensors comprising a boronic acid-appended fluorescence quencher together with an aminopyrene fluorophore were prepared in a matter of hours in multiwell plates. The sensors showed good reproducibility in response to solutions of glucose at physiological pH. Dried glucose sensors rehydrated with analyte solution performed similarly to freshly prepared hydrogels. The loaded plates are designed for use in high throughput screening applications. Plates were prepared using the redox initiator system metabisulfite/persulfate/iron(II) to generate hydrogels of N,N-dimethylacrylamide crosslinked with N,N′-methylenebisacrylamidein situ.

Potential photoactivated metallopharmaceuticals: from active molecules to supported drugs

Co-reporter:Daniel Crespy, Katharina Landfester, Ulrich S. Schubert and Alexander Schiller

Chemical Communications 2010 vol. 46(Issue 36) pp:6651-6662

Publication Date(Web):18 Aug 2010

DOI:10.1039/C0CC01887B

Apart from cisplatin and some derivatives successful metallopharmaceuticals are still scarce in antitumour therapy. Although novel metal complexes have been investigated in preclinical settings several promising compounds failed in different phases. With the rise of new anticancer compounds new activation strategies have also evolved. Photochemical activation is one of the most important concepts as it uses pro-drugs whose activity can be triggered by light. This strategy offers the possibility to control the location, timing, and dosage of the therapeutic metal complex. Recent developments in the photoactivation of potential metallopharmaceuticals are summarized. Immobilisation of those drugs on solid matrices, such as films, particles, gels, and fibers, is an emerging field and recent findings are also discussed.

Enzyme assays with boronic acid appended bipyridinium salts

Co-reporter:Boaz Vilozny, Alexander Schiller, Ritchie A. Wessling, Bakthan Singaram

Analytica Chimica Acta 2009 Volume 649(Issue 2) pp:246-251

Publication Date(Web):7 September 2009

DOI:10.1016/j.aca.2009.07.032

In-vitro fluorescent enzyme assays have been developed for sucrose phosphorylase (SPO) and phosphoglucomutase (PGM). These assays make use of a selective carbohydrate sensing system that detects the unlabeled enzymatic products fructose and glucose-6-phosphate. The system comprises 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt as the reporter unit and boronic acid appended viologens as selective receptors with working ranges from 70 μM to 1.0 mM for fructose (SPO) and 190 μM to 2.0 mM for glucose-6-phosphate (PGM). The change in fluorescence can be converted into product concentration, allowing initial reaction velocities and Michaelis–Menten kinetics to be calculated. The assays are also carried out in multiwell plate formats, making them suitable for high-throughput screening of enzyme inhibitors. Rapid PGM inhibition screening is demonstrated with EDTA and LiCl. The PGM assay can also be used for enzyme quantification with a detection limit of 50 ng mL−1.

Potential photoactivated metallopharmaceuticals: from active molecules to supported drugs

Co-reporter:Daniel Crespy, Katharina Landfester, Ulrich S. Schubert and Alexander Schiller

Chemical Communications 2010 - vol. 46(Issue 36) pp:NaN6662-6662

Publication Date(Web):2010/08/18

DOI:10.1039/C0CC01887B

Apart from cisplatin and some derivatives successful metallopharmaceuticals are still scarce in antitumour therapy. Although novel metal complexes have been investigated in preclinical settings several promising compounds failed in different phases. With the rise of new anticancer compounds new activation strategies have also evolved. Photochemical activation is one of the most important concepts as it uses pro-drugs whose activity can be triggered by light. This strategy offers the possibility to control the location, timing, and dosage of the therapeutic metal complex. Recent developments in the photoactivation of potential metallopharmaceuticals are summarized. Immobilisation of those drugs on solid matrices, such as films, particles, gels, and fibers, is an emerging field and recent findings are also discussed.

Light-triggered CO release from nanoporous non-wovens

Co-reporter:Carmen Bohlender, Steve Gläser, Moritz Klein, Jürgen Weisser, Susanne Thein, Ute Neugebauer, Jürgen Popp, Ralf Wyrwa and Alexander Schiller

Journal of Materials Chemistry A 2014 - vol. 2(Issue 11) pp:NaN1463-1463

Publication Date(Web):2014/02/11

DOI:10.1039/C3TB21649G

The water insoluble and photoactive CO releasing molecule dimanganese decacarbonyl (CORM-1) has been non-covalently embedded into poly(L-lactide-co-D/L-lactide) fibers via electrospinning to enable bioavailability and water accessibility of CORM-1. SEM images of the resulting hybrid non-wovens reveal a nanoporous fiber morphology. Slight CO release from the CORM-1 in the electrospinning process induces nanoporosity. IR spectra show the same set of carbonyl bands for the CORM-1 precursor and the non-woven. When the material was exposed to light (365–480 nm), CO release from the incorporated CORM-1 was measured via heterogeneous myoglobin assay, a portable CO electrode and an IR gas cuvette. The CO release rate was wavelength dependent. Irradiation at 365 nm resulted in four times faster release than at 480 nm. 3.4 μmol of CO per mg non-woven can be generated. Mouse fibroblast 3T3 cells were used to show that the hybrid material is non-toxic in the darkness and strongly photocytotoxic when light is applied.

Light-triggered NO release from a nanofibrous non-woven

Co-reporter:Carmen Bohlender;Martin Wolfram;Helmar Goerls;Wolfgang Imhof;Roberto Menzel;Anja Baumgaertel;Ulrich S. Schubert;Ulrike Mueller;Martina Frigge;Matthias Schnabelrauch;Ralf Wyrwa

Journal of Materials Chemistry A 2012 - vol. 22(Issue 18) pp:

Publication Date(Web):2012/04/10

DOI:10.1039/C2JM15410B

Light-controlled NO delivery systems promise new applications in phototherapies. For this purpose, a ruthenium nitrosyl complex [(2)Ru(NO)(Cl)] with the novel ligand N,N′-(1,2-phenylene)bis(1-methyl-1H-imidazole-2-carboxamide) (2) has been synthesised and characterised in detail. The photoactive {Ru–NO}6 nitrosyl released NO in DMSO upon exposure to low-intensity UV-A light (λ = 366 nm). In order to create an applicable system the water-insoluble [(2)Ru(NO)(Cl)] was embedded into poly(L-lactide-co-D/L-lactide) nanofibrous non-wovens by electrospinning. Exposure of a 25 wt% non-woven of [(2)Ru(NO)(Cl)] to UV-A light resulted in a continuous release of NO into an aqueous solution. The cytoxicity of the non-woven against 3T3 mouse fibroblasts was very low.

Carbon monoxide – physiology, detection and controlled release

Co-reporter:Stefan H. Heinemann, Toshinori Hoshi, Matthias Westerhausen and Alexander Schiller

Chemical Communications 2014 - vol. 50(Issue 28) pp:NaN3660-3660

Publication Date(Web):2014/02/21

DOI:10.1039/C3CC49196J

Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed.

Multiwell plates loaded with fluorescent hydrogel sensors for measuring pH and glucose concentration

Co-reporter:Boaz Vilozny, Alexander Schiller, Ritchie A. Wessling and Bakthan Singaram

Journal of Materials Chemistry A 2011 - vol. 21(Issue 21) pp:NaN7595-7595

Publication Date(Web):2011/03/21

DOI:10.1039/C0JM04257A

Fluorescent hydrogels were polymerized directly in multi-well plates at ambient temperature and in the presence of air, producing sensors for measuring pH and glucose concentration. The plates were rapidly analyzed using a fluorescence plate reader. Multiwell pH sensors with good reproducibility among different wells and a dynamic range from pH 6 to 9 were prepared by incorporating a polymerizable pH sensitive fluorophore in the hydrogel. Non-enzymatic glucose sensors comprising a boronic acid-appended fluorescence quencher together with an aminopyrene fluorophore were prepared in a matter of hours in multiwell plates. The sensors showed good reproducibility in response to solutions of glucose at physiological pH. Dried glucose sensors rehydrated with analyte solution performed similarly to freshly prepared hydrogels. The loaded plates are designed for use in high throughput screening applications. Plates were prepared using the redox initiator system metabisulfite/persulfate/iron(II) to generate hydrogels of N,N-dimethylacrylamide crosslinked with N,N′-methylenebisacrylamidein situ.

Remote-controlled delivery of CO via photoactive CO-releasing materials on a fiber optical device

Co-reporter:Steve Gläser, Ralf Mede, Helmar Görls, Susanne Seupel, Carmen Bohlender, Ralf Wyrwa, Sina Schirmer, Sebastian Dochow, Gandra Upendar Reddy, Jürgen Popp, Matthias Westerhausen and Alexander Schiller

Dalton Transactions 2016 - vol. 45(Issue 33) pp:NaN13233-13233

Publication Date(Web):2016/07/08

DOI:10.1039/C6DT02011A

Although carbon monoxide (CO) delivery materials (CORMAs) have been generated, remote-controlled delivery with light-activated CORMAs at a local site has not been achieved. In this work, a fiber optic-based CO delivery system is described in which the photoactive and water insoluble CO releasing molecule (CORM) manganese(I) tricarbonyl [(OC)3Mn(μ3-SR)]4 (R = nPr, 1) has been non-covalently embedded into poly(L-lactide-co-D/L-lactide) and poly(methyl methacrylate) non-woven fabrics via the electrospinning technique. SEM images of the hybrid materials show a porous fiber morphology for both polymer supports. The polylactide non-woven fabric was attached to a fiber optical device. In combination with a laser irradiation source, remote-controlled and light-triggered CO release at 405 nm excitation wavelength was achieved. The device enabled a high flexibility of the spatially and timely defined application of CO with the biocompatible hybrid fabric in aqueous media. The rates of liberated CO were adjusted with the light intensity of the laser. CO release was confirmed via ATR-IR spectroscopy, a portable electrochemical CO sensor and a heterogeneous myoglobin assay.