Christoph Böttcher

Freie Universität Berlin, Berlín, Berlin, Germany

Are you Christoph Böttcher?

Claim your profile

Publications (146)745.37 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: This report describes the synthesis, structure, and O2-binding properties of core–shell clusters composed of human haemoglobin A (HbA) in the centre and human serum albumins (HSAs) at the periphery (HbA-HSAm) as a potential O2-carrier designed as a red blood cell (RBC) substitute. Protein clusters were prepared by covalent linkage between HbA lysins and HSA cysteine-34 using heterobifunctional cross-linker, succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate. Major products (m = 2, 3, 4) were isolated using gel filtration chromatography. The low isoelectric points (pI = 5.0–5.2) of the clusters were almost identical to that of HSA, proving the wrapping of HbA by negatively charged HSA. The 3D reconstruction of HbA-HSA3 based on transmission electron microscopy images revealed a complete triangular structure. The proposed geometries enabled us to assign a possible spatial arrangement of the HbA centre and HSA periphery. The HbA-HSAm clusters showed higher O2-affinities (P50 = 8–9 Torr) than the native HbA. Clusters prepared under N2 atmosphere showed low O2-affinity (P50 = 26 Torr) resembling human RBC. Moreover, the cluster containing an αα-cross-linked HbA with a bis(3,5-dibromosalicyl)fumarate showed markedly low O2-affinity (P50 = 35 Torr). These HbA-HSAm clusters with various O2-affinities can support a new generation of RBC substitutes that is better tuned to a role in O2 transport.
    06/2015; DOI:10.1039/C5TB00540J
  • [Show abstract] [Hide abstract]
    ABSTRACT: Engineering nanostructures of defined size and morphology is a great challenge in the field of self-assembly. Herein we report on the formation of supramolecular nanostructures of defined morphologies with subtle structural changes for a new series of dendritic amphiphiles. Subsequently, we studied their application as nanocarriers for guest molecules.
    Chemical Communications 03/2015; 51(41). DOI:10.1039/C4CC09513H · 6.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The first highly water-soluble perylene-calix[4]arene-hybrid with the calixarene scaffold acting as a structure determining central platform is presented. In this tetrahedrally shaped amphiphilic architecture the hydrophilic and hydrophobic subunits are oriented ate the opposite side of the calixarene platform. The hydrophobic part contains the two perylenediimide moieties, which enable strong π-π-interactions in self-assembly processes. Two hydrophilic Newkome-type dendrons provide sufficient water solubility at slightly basic conditions. The tetrahedrally shaped amphiphile dis-plays an unprecedented aggregation behavior down to concentrations as low as 10 7 mol L 1. The intriguing self-assembly process of the compound in water as well as under changed polarity conditions, achieved by addition of THF, could be monitored by the complemented use of cryogenic transmission electron microscopy (cryo-TEM), UV/Vis- and fluores-cence spectroscopy. Molecular-dynamics (MD) and molecular modelling simulations helped in understanding the inter-play of supramolecular and optical behavior.
    Journal of the American Chemical Society 02/2015; 137(9). DOI:10.1021/ja512048t · 11.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Competitive binding inhibitors based on multivalent nanoparticles have shown great potential for preventing virus infections. However, general design principles of highly efficient inhibitors are lacking as the quantitative impact of factors such as virus concentration, inhibitor size, steric shielding or multivalency effects in the inhibition process is not known. Based on two complementary experimental inhibition assays we could determine and even predict size-dependent steric shielding and multivalency effects. This allowed us to adapt the Cheng-Prusoff equation for its application to multivalent systems. Our results showed that the particle and volume normalized IC50 value of an inhibitor at very low virus concentrations predominantly depends on its multivalent association constant, which itself exponentially increases with the inhibitor/virus contact area and ligand density. Compared to multivalency effects, the contribution of steric shielding to the IC50 values is only minor and its impact is only noticeable if the multivalent dissociation constant is far below the virus concentration, which means if all inhibitors are bound to the virus. The dependence of the predominant effect, either steric shielding, or multivalency, on the virus concentration has significant implications on the in vitro testing of competitive binding inhibitors and determines optimal inhibitor diameters for the efficient inhibition of viruses.
    Journal of the American Chemical Society 01/2015; DOI:10.1021/ja5114084 · 11.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Photoresponsive polymeric amphiphiles were developed by first synthesizing the polyester chain via Novozym 435 catalyzed step growth, condensation polymerization of poly[ethylene glycol bis(carboxymethyl) ether]diethylester and 2-azidopropan-1,3-diol followed by its grafting with 4'-butyl-4-propargyloxy(azobenzene) and [G2.0] polyglycerol dendron by using ‘Click chemistry’ approach. The resulting polymers were observed to form supramolecular micellar aggregates in the aqueous solution. The critical aggregation concentration (CAC) was determined via fluorescence measurements and using ‘Nile red’ as a probe. The nano-structures formed in the aqueous solution were characterized by dynamic light scattering (DLS) and cryo-TEM measurements. The encapsulation potential of polymeric amphipihiles for Nile red and curcumin as well as their release via trans-cis photoisomerization of the embedded azobenzene moiety was studied, by absorbance and fluorescence spectroscopy techniques. The developed polymeric micellar systems behave as efficient photoresponsive smart nanocarriers.
    RSC Advances 01/2015; 5(60). DOI:10.1039/C5RA08047A · 3.71 Impact Factor
  • Daniel Schöne, Boris Schade, Christoph Böttcher, Beate Koksch
    Beilstein Journal of Organic Chemistry 01/2015; 11:792-803. DOI:10.3762/bjoc.11.89 · 2.80 Impact Factor
  • Changzhu Wu, Christoph Boettcher, Rainer Haag
    [Show abstract] [Hide abstract]
    ABSTRACT: The enormous potential of nanogel scaffolds for protein encapsulation has been widely recognized. However, constructing stable polymeric nanoscale networks in a facile, mild, and controllable fashion still remains a technical challenge. Here, we present a novel nanogel formation strategy using horseradish peroxidase (HRP) catalyzed crosslinking on phenolic derivatized dendritic polyglycerol (dPG) in the presence of H2O2 in an inverse miniemulsion. This “enzymatic nanogelation” approach was efficient to produce stable 200 nm dPG nanogel particles, and was performed under physiological conditions, thus making it particularly beneficial for encapsulating biological proteins. Purification of the nanogels was easy to handle and practical because there was no need for a post-quenching step. Interestingly, the use of dPG resulted in higher HRP laden nanogels than for linear polyethylene glycol (PEG) analogs, which illustrates the benefits of dendritic backbones in nanogels for protein encapsulation. In addition, the mild immobilization contributed to the enhanced thermal stability and reusability of HRP. The nanogel preparation could be easily optimized to achieve the best HRP activity. Furthermore, a second enzyme, Candida antarctica lipase B (CalB), was successfully encapsulated and optimized for activity in dPG nanogels by the same enzymatic methodology, which shows the perspective applications of such techniques for encapsulation of diverse proteins.
    Soft Matter 12/2014; 11(5). DOI:10.1039/C4SM01746C · 4.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Two core-shell nanoparticles with polyglycerol shells and sp3 carbon cores with different flexibilities (soft dendritic polyethylene and hard nanodiamond) were synthesized, their encapsulation capacities were compared, and their ability to transport into tumor cells was investigated. The nanocarrier with a soft core was superior to the hard one.
    12/2014; 3(5). DOI:10.1039/C4TB01858C
  • [Show abstract] [Hide abstract]
    ABSTRACT: Here we report for the first time on a microwave assisted synthesis of polyglycerol dendron functionalized cyclodextrins (CD) with hydrophobic tails. These amphiphilic CDs consist of seven polyglycerol dendrons and fourteen alkyl chains on the primary and secondary rims of the cyclodextrin core, respectively. They self-assemble to form nanostructures in aqueous solutions and efficiently encapsulate hydrophobic aromatic guests. Size and shape of self-assemblies and also their ability to encapsulate guest molecules depend on the generation of conjugated polyglycerol dendrons.
    RSC Advances 11/2014; DOI:10.1039/C4RA11601A · 3.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Supramolecular polymerization for non-wetting surface coatings is described. The self-assembly of low-molecular-weight gelators (LMWGs) with perfluorinated side chains can be utilized to rapidly construct superhydrophobic as well as liquid-infused slippery surfaces within minutes. The lubricated slippery surface exhibits impressive repellency to biological li-quids, such as human serum and blood, and very fast self-healing.
    Advanced Materials 11/2014; 26(43). DOI:10.1002/adma.201401366 · 15.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To gain insight into the factors that affect stability and transport efficiency under dilution conditions, dendronized and hyperbranched multifunctional amphiphilic polymers are synthesized by following the "grafting to" approach using varied amounts of propargylated alkyl chain with perfect and hyperbranched polyglycerol dendrons on the base copolymer of PEG (M¯n: 1000 g mol(-1) ) diethylester and 2-azidopropane-1,3-diol following the "bio-catalytic method" and "click approach". The dendronized and hyperbranched polymeric systems form supramolecular aggregates and exhibit an efficient transport potential for the model dye "Nile red" in the low μm range in the core-shell-type architecture provided with distinct amphiphilicity as required for encapsulation. Cytotoxicity studies show the polymeric systems to be non-toxic over a wide concentration range. The cellular internalization of Nile-red-encapsulated supramolecular micellar structures is also studied using cellular fluorescence micro-scopy and fluorescence-activated cell sorting (FACS) measurements. A comparison of the data for the dendronized polymers (PEG M¯n: 600/1000 g mol(-1) ) with the respective low-molecular-weight amphiphile reveal that these polymeric systems are excellent nanotransporters.
    Macromolecular Rapid Communications 11/2014; 36(2). DOI:10.1002/marc.201400467 · 4.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A covalent core-shell structured protein cluster composed of hemoglobin (Hb) at the center and human serum albumins (HSA) at the periphery, Hb-HSAm, is an artificial O2 carrier that can function as a red blood cell substitute. Here we described the preparation of a novel Hb-HSA3 cluster with antioxidant activities and its O2 complex stable in aqueous H2O2 solution. We used an approach of incorporating a Pt nanoparticle (PtNP) into the exterior HSA unit of the cluster. A citrate reduced PtNP (1.8 nm diameter) was bound tightly within the cleft of free HSA with a binding constant (K) of 1.1×107 M-1, generating a stable HSA-PtNP complex. This platinated protein showed high catalytic activities for dismutations of superoxide radical anions (O2•-) and hydrogen peroxide (H2O2), i.e., superoxide dismutase and catalase activities. Also, Hb-HSA3 captured PtNP into the external albumin unit (K = 1.1×107 M-1), yielding an Hb-HSA3(PtNP) cluster. The association of PtNP caused no alteration of the protein surface net charge and O2 binding affinity. The peripheral HSA-PtNP shell prevents oxidation of the core Hb, which enables the formation of an extremely stable O2 complex, even in H2O2 solution.
    PLoS ONE 10/2014; 9(10):e110541. DOI:10.1371/journal.pone.0110541 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The self-assembly of amphiphilic molecules into fibrous structures has been the subject of numerous studies over past decades due to various current and promising technical applications. Although very different in their head group chemistry many natural as well as synthetic amphiphilic compounds derived from carbohydrates, carbocyanine dyes, or amino acids tend to form fibrous structures by molecular self-assembly in water predominantly twisted ribbons or tubes. Often a transition between these assembly structures is observed, which is a phenomenon already theoretically approached by Wolfgang Helfrich and still focus point in current research. With the development of suitable sample preparation and electron optical imaging techniques, cryogenic transmission electron microscopy (cryo-TEM) in combination with three-dimensional (3D) reconstruction techniques has become a particular popular direct characterization technique for supramolecular assemblies in general. Here we review the recent progress in deriving precise structural information from cryo-TEM data of particularly fibrous structures preferably in three dimensions.
    Advances in Colloid and Interface Science 06/2014; 208. DOI:10.1016/j.cis.2014.01.007 · 8.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of novel functionalised dumbbell-shaped bifullerenes in which two [5.0] pentakis-adducts of C60 are covalently connected by cyclic bismalonates were synthesised. These dimeric compounds, carrying various combinations of hydrophilic and hydrophobic addends, self-assemble in aqueous solution towards supramolecular architectures of different structural complexity as observed by cryogenic transmission electron microscopy (cryo-TEM). The detailed analysis of the image data revealed an unprecedented hierarchical aggregation behaviour. Whereas completely hydrophilic substituted bifullerenes formed profoundly monodisperse populations of small oligomeric elementary micelles consisting of only three or four bifullerene molecules in a supposedly bent conformation, their amphiphilic equivalents underwent a hierarchical two-step assembly process towards larger spherical and even rod-like structures. The data suggest that the hierarchical assembly process is driven by hydrophobic interactions of preformed tetrameric elementary micelles.
    Chemistry - A European Journal 05/2014; 20(20):5961-6. DOI:10.1002/chem.201400153 · 5.70 Impact Factor
  • Hans von Berlepsch, Kai Ludwig, Christoph Böttcher
    [Show abstract] [Hide abstract]
    ABSTRACT: The aggregation behaviour of the cationic pinacyanol chloride in aqueous solution is investigated using absorption and linear dichroism spectroscopies, optical microscopy and cryogenic transmission electron microscopy (cryo-TEM). The investigations are focused on solutions in a concentration range from 50 μM up to 1 mM. At a concentration of 0.7 mM H-aggregates are detected that are characterized by a broad absorption band centred at ∼511 nm. The aggregates possess a tubular architecture with a single-layer wall thickness of ∼2.5 nm and an outer diameter of ∼6.5 nm. Linear dichroism spectroscopy indicates that the molecules are packed with their long axis parallel to the tube axis. These H-aggregates are not stable, but transform into J-aggregates on the time scale of weeks. The kinetics of J-aggregation depends on the dye concentration and the route of sample preparation, but can also be enhanced by shear stress. J-aggregates possess a split absorption spectrum composed of two longitudinally polarized J-bands and one H-band that is polarized perpendicular to the aggregate axis. The J-aggregates are ∼9 nm wide and several micrometer long fibrils consisting of stacked pairs of ribbons with a dumbbell-shaped density cross-section. Upon aging these ribbons laterally stack face-to-face to form tape-like aggregates.
    Physical Chemistry Chemical Physics 04/2014; 16(22). DOI:10.1039/c4cp00967c · 4.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We have synthesized a targeted imaging agent for rheumatoid arthritis based on polysulfated gold nanorods. The CTAB layer on gold nanorods was first replaced with PEG-thiol and then with dendritic polyglycerolsulfate at elevated temperature, which resulted in significantly reduced cytotoxicity compared to polyanionic gold nanorods functionalized by non-covalent approaches. In addition to classical characterization methods, we have established a facile UV-VIS based BaCl2 agglomeration assay to confirm a quantitative removal of unbound ligand. With the help of a competitive surface plasmon resonance-based L-selectin binding assay and a leukocyte adhesion-based flow cell assay, we have demonstrated the high inflammation targeting potential of the synthesized gold nanorods in vitro. In combination with the surface plasmon resonance band of AuNRs at 780 nm, these findings permitted the imaging of inflammation in an in vivo mouse model for rheumatoid arthritis with high contrast using multispectral optoacoustic tomography. The study offers a robust method for otherwise difficult to obtain covalently functionalized polyanionic gold nanorods, which are suitable for biological applications as well as a low-cost, actively targeted, and high contrast imaging agent for the diagnosis of rheumatoid arthritis. This paves the way for further research in other inflammation associated pathologies, in particular, when photothermal therapy can be applied.
    Theranostics 03/2014; 4(6):629-41. DOI:10.7150/thno.8518 · 7.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of antiviral agents is one of the major challenges in medical science. So far, small monovalent molecular drugs that inhibit the late steps in the viral replication cycle, i.e., virus budding, have not worked well which emphasizes the need for alternative approaches. Polyvalently presented viral receptors, however, show potential as good inhibitors of virus-cell binding, which is the first step in the viral infection cycle. By gradually increasing the size of ligand functionalized gold nanoparticles, up to virus-like dimensions, we are now able to quantify the polyvalent enhancement of virus-cell binding inhibition and to identify varying mechanisms of virus inhibition with different efficacies: by employing a new binding assay we found that surface area-normalized polysulfated gold nanoparticles of diameters equal to and larger than the virus diameter (>50 nm) more efficiently inhibit the binding of vesicular stomatitis virus (VSV) to cells than smaller particles. On a per particle basis, larger sized gold nanoparticles were surprisingly shown to inhibit the viral infection up to two orders of magnitude more efficiently than smaller particles, which suggests different mechanisms of virus inhibition. Based on complementary electron microscopic data, we noticed that larger gold nanoparticles act as efficient cross-linkers between virions, whereas smaller gold nanoparticles decorate the surface of individual virus particles. Our systematic study accentuates the need for the design of biodegradable, virus-sized inhibitors capitalizing on polyvalent binding.
    Nanoscale 01/2014; 6(4). DOI:10.1039/c3nr04449a · 6.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An amphiphilic linear ternary block copolymer was synthesised in three consecutive steps via reversible addition–fragmentation chain transfer polymerisation. Oligo(ethylene glycol) monomethyl ether acrylate was engaged as a hydrophilic building block, while benzyl acrylate and 3-tris(trimethylsiloxy)silyl propyl acrylate served as hydrophobic building blocks. The resulting “triphilic” copolymer consists thus of a hydrophilic (A) and two mutually incompatible “soft” hydrophobic blocks, namely, a lipophilic (B) and a silicone-based (C) block, with all blocks having glass transition temperatures well below 0 °C. The triphilic copolymer self-assembles into spherical multicompartment micellar aggregates in aqueous solution, where the two hydrophobic blocks undergo local phase separation into various ultrastructures as evidenced by cryogenic transmission electron microscopy. Thus, a silicone-based polymer block can replace the hitherto typically employed fluorocarbon-based hydrophobic blocks in triphilic block copolymers for inducing multicompartmentalisation.
    Colloid and Polymer Science 11/2013; 291(11). DOI:10.1007/s00396-013-3001-2 · 2.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report a novel nanostructured organosalt, based on sulfonic acid functionalized pyrazinium {[H-pyrazine–SO3H]Cl2} that was synthesized and characterized by several techniques including Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), thermal gravimetric analysis (TGA), differential thermal gravimetric (DTG) analysis, transmission electron microscopy (TEM), mass spectrometry (MS), proton NMR (1H NMR), carbon-13 NMR (13C NMR) and also electron diffraction (ED) patterns. Results proved that the unprecedented sulfonated pyrizinium organosalt is indeed nanostructured and highly crystalline as supported by TEM, ED and XRD studies, having an average nanoparticle size of 50 nm according to TEM micrographs. The novel nano-organocatalyst was proved to be an efficient catalyst in the synthesis of 1,2,4,5-tetrasubstituted imidazoles by a one-pot multi-component condensation of benzil, a broad range of aldehydes, primary amines and ammonium acetate at 90 °C under solvent-free conditions.
    Journal of Materials Chemistry 10/2013; 2(3). DOI:10.1039/C3TA13484A · 7.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We describe the synthesis, structure, and catalytic activity of human serum albumin (HSA) nanotubes (NTs) including gold nanoparticles (AuNPs) as a layered wall component. The NTs were fabricated as an alternating layer-by-layer assembly of AuNP and HSA admixture (a negatively charged part) and poly-L-arginine (PLA, a positively charged part) into a track-etched polycarbonate membrane (400 nm pore diameter), with subsequent dissolution of the tem-plate. SEM images showed the formation of uniform hollow cylinders of (PLA/AuNP-HSA)3 with a 426 ± 12 nm outer diameter and 65 ± 7 nm wall thickness. TEM and EDX measurements revealed high loading of AuNPs in the tubular wall. HSAs bind strongly onto the individual AuNP (K = 1.25 × 109 M-1), generating a core-shell AuNP-HSA conju-gate, which is the requirement of the robust NT formation. Calcination of the (PLA/AuNP-HSA)3 NTs at 500 °C under air yielded red solid NTs composed of thermally fused AuNPs. From the mass decrease by heat treatment, we calcu-lated the weight of the organic components (PLA and HSA) and thereby constructed a six-layer model of the tube. The (PLA/AuNP-HSA)3 NTs serves as a heterogeneous catalyst for reduction of 4-nitrophenol with sodium borohydrate. Furthermore, implantation of the stiff (PLA/AuNP-HSA)3 NTs vertically onto glass plate produced uni-formly cylindrical tube arrays.
    Langmuir 10/2013; 29(46). DOI:10.1021/la403283x · 4.38 Impact Factor

Publication Stats

3k Citations
745.37 Total Impact Points

Institutions

  • 1990–2014
    • Freie Universität Berlin
      • • Institute of Chemistry and Biochemistry
      • • Division of Organic Chemistry
      • • Division of Inorganic Chemistry
      Berlín, Berlin, Germany
  • 2004–2010
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • Department of Chemistry and Pharmacy
      Erlangen, Bavaria, Germany
  • 2009
    • Technische Universität Berlin
      • Department of Chemistry
      Berlín, Berlin, Germany
  • 1997–2008
    • Humboldt University of Berlin
      • Faculty of Mathematics and Natural Sciences I
      Berlín, Berlin, Germany
  • 2007
    • Universiteit Utrecht
      • Department of Infectious Diseases and Immunology
      Utrecht, Utrecht, Netherlands
  • 2003–2005
    • University of Leipzig
      • Institute of Organic Chemistry
      Leipzig, Saxony, Germany
  • 2000
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 1996
    • Waseda University
      Edo, Tōkyō, Japan
    • Fritz Haber Institute of the Max Planck Society
      Berlín, Berlin, Germany