Jacobs University Bremen gGmbH Campus Ring 1 D-28759 Bremen
The group is working in two different areas. One area is focused on the use of boron clusters as new entities for drugs and in supramolecular chemistry. The clusters have unique properties which are not found in organic or other inorganic molecules. They are the first anions which bind strongly to supramolecular hosts such as cyclodextrins and cucurbiturils. Due to the unusual properties of the cluster, their interaction with biological membranes is unexpected. The necessary methods for synthesizing derivatives of these clusters are being pursued.
The other area deals with the development of new dyes for ocular surgery. The aim is to develop better dyes, especially for visualization of the internal limiting membrane. This work includes synthesis, testing for toxicity in vitro, staining in suitable models, and collaboration with ophthalmologists for eventual application in the clinic.
- Lipids for boron neutron capture therapy
Lipids are being developed for treatment of cancer by boron neutron capture therapy (BNCT). These lipids carry the promise to be superior to low-molecular weight compounds. The lipids are synthesized in the group and then are tested for toxicity and biodistribution in suitable models.
Luyi Wang (PhD student), Project: Development and testing of boron-containing lipids
- Boron cluster compounds as enzyme inhibitors
Boron clusters have recently been identified as new and unusual pharmacophores in medicinal chemistry. They have been described as inhibitors of acetylcholinesterase, HIV protease, and cyclic oxygenase. In this project, suitable synthetic methods for greater chemical versatility are being developed, and analogs of known enzyme inhibitors are synthesized and tested.
Arsen Galustyan (PhD student), Project: Synthesis and testing of enzyme inhibitors containing boron clusters as pharmacophores
- Molecular dynamics of boron clusters in water
In collaboration with Prof. Roccatano, molecular dynamics studies of boron clusters in water are being pursued. These studies are aimed at understanding the unusual properties of ionic boron clusters and their interaction with biological interfaces.
- Action of boron clusters on lipid membranes
We have recently shown that boron clusters strongly influence membranes both in their structure and their integrity. These observations are being investigated with respect to improvement of liposomes as drug delivery agents.
- Gas phase dimerization of boron clusters
In mass spectrometry, boron clusters can dimerize. The structure of these dimers is being explored through quantum-mechanical computations in collaboration with Prof. Heine and Dr. Vankova.
Lei Liu (PhD student), Project: Elucidation of dimer structures and dimerization pathways of iodinated dodecaborates
Toxicity of chemicals on eyes
- Validation of a cornea model
Toxicity of chemicals on the eye cornea must be known, when the chemicals are marketed. This is presently done in animals. In a BMBF-financed project, a recently developed cornea model is being validated as replacement of animal tests.
Melinda Bartok (PhD student), Project: Validation and improvement of a cornea model
- Combination toxicity
In eye surgery, pathological membranes formed on the retina are removed in order to restore the sight. Clinically, it was found that the removal of the internal limiting membrane leads to even better and permanent restoration of the visual acuity. Dyes are being used to stain these membranes for better visualization. We investigate whether combinations of dyes, which give superior staining of membranes, can be used safely.
Melinda Bartok (PhD student), Project:Combination toxicity of dyes for ocular surgery
Assaf, K. I., A. Hennig, S. Peng, D.-S. Guo, D. Gabel and W. M. Nau (2017). “Hierarchical host-guest assemblies formed on dodecaborate-coated gold nanoparticles.” Chem. Commun. 53: 4616-4619.
Assaf, K. I., D. Gabel, W. Zimmermann and W. M. Nau (2016). “High-affinity host-guest chemistry of large-ring cyclodextrins.” Org. Biomol. Chem. 14: 7702-7706.
Assaf, K. I., O. Suckova, N. Al Danaf, V. von Glasenapp, D. Gabel and W. M. Nau (2016). “Dodecaborate-Functionalized Anchor Dyes for Cyclodextrin-Based Indicator Displacement Applications.” Org Lett 18: 932-935.
Assaf, K. I., M. S. Ural, F. Pan, T. Georgiev, S. Simova, K. Rissanen, D. Gabel and W. M. Nau (2015). “Water Structure Recovery in Chaotropic Anion Recognition: High-Affinity Binding of Dodecaborate Clusters to gamma-Cyclodextrin.” Angew. Chem. Int. Ed. Engl. 54: 6852-6856.
Awad, D., M. Bartok, F. Mostaghimi, I. Schrader, N. Sudumbrekar, T. Schaffran, C. Jenne, J. Eriksson, M. Winterhalter, J. Fritz, K. Edwards and D. Gabel (2015). “Halogenated Dodecaborate Clusters as Agents to Trigger Release of Liposomal Contents.” ChemPlusChem 80: 656-664.
Bartok, M., D. Gabel, M. Zorn-Kruppa and M. Engelke (2015). “Development of an in vitro ocular test system for the prediction of all three GHS categories.” Toxicol In Vitro 29: 72-80.
Bartok, M., R. Tandon, G. Alfaro-Espinoza, M. S. Ullrich and D. Gabel (2015). “Reduction of cytotoxicity of benzalkonium chloride and octenidine by Brilliant Blue G.” Excli Journal 14: 123-132.
Gabel, D. (2015). “Boron clusters in medicinal chemistry: perspectives and problems.” Pure & Applied Chemistry 87: 173-179.
Tandon, R., M. Bartok, M. Zorn-Kruppa, J. M. Brandner, D. Gabel and M. Engelke (2015). “Assessment of the eye irritation potential of chemicals: A comparison study between two test methods based on human 3D hemi-cornea models.” Toxicol In Vitro 30: 561-568.
Assaf KI, Ural MS, Pan F, Georgiev T, Simova S, Rissanen K, Gabel D, Nau WM (2015) Water Structure Recovery in Chaotropic Anion Recognition: High-Affinity Binding of Dodecaborate Clusters to gamma-Cyclodextrin. Angew Chem Int Ed Engl 54: 6852-6856
Awad D, Bartok M, Mostaghimi F, Schrader I, Sudumbrekar N, Schaffran T, Jenne C, Eriksson J, Winterhalter M, Fritz J, Edwards K, Gabel D (2015) Halogenated Dodecaborate Clusters as Agents to Trigger Release of Liposomal Contents. ChemPlusChem 80: 656-664
Bartok M, Gabel D, Zorn-Kruppa M, Engelke M (2015) Development of an in vitro ocular test system for the prediction of all three GHS categories. Toxicology in Vitro 29: 72-80
Bartok M, Tandon R, Alfaro-Espinoza G, Ullrich MS, Gabel D (2015) Reduction of cytotoxicity of benzalkonium chloride and octenidine by Brilliant Blue G. Excli Journal 14: 123-132
Fan P, Stolte S, Gabel D (2014) Interaction of organic compounds and boron clusters with new silica matrices containing the phosphatidylcholine headgroup. Anal Methods 6: 3045-3055
Sander A, Wosniok W, Gabel D (2014) Case numbers for a randomized clinical trial of boron neutron capture therapy for Glioblastoma multiforme. Appl Radiat Isot 88: 16-19
Schaffran T, Jiang N, Bergmann M, Küstermann E, Süss R, Schubert R, Wagner FM, Awad D, Gabel D (2014) Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy. Int J Nanomed 9: 3583—3590
Awad D, Schrader I, Bartok M, Sudumbrekar N, Mohr A, Gabel D (2013) Brilliant Blue G as protective agent against trypan blue toxicity in human retinal pigment epithelial cells in vitro. Graefes Arch Clin Exp Ophthalmol 251: 1735-1740
Engelke M, Zorn-Kruppa M, Gabel D, Reisinger K, Rusche B, Mewes KR (2013) A human hemi-cornea model for eye irritation testing: quality control of production, reliability and predictive capacity. Toxicology in vitro : an international journal published in association with BIBRA 27: 458-468
Mohr A, Bruinsma M, Oellerich S, Frank H, Gabel D, Melles GR (2013) Dyes for eyes: hydrodynamics, biocompatibility and efficacy of ‘heavy’ (dual) dyes for chromovitrectomy. Ophthalmologica Journal international d’ophtalmologie International journal of ophthalmology Zeitschrift fur Augenheilkunde 230 Suppl 2: 51-58
Wöhrle D, Tsaryova O, Semioshkin A, Gabel D, Suvorova O (2013) Synthesis and photochemical properties of phthalocyanine zinc(II) complexes containing o-carborane units. J Organomet Chem 747: 98-105
Zeonjuk LL, Vankova N, Knapp C, Gabel D, Heine T (2013) On the gas-phase dimerization of negatively charged closo-dodecaborates: a theoretical study. Phys Chem Chem Phys 15: 10358-10366
Fan, P., J. Neumann, S. Stolte, J. Arning, D. Ferreira, K. Edwards and D. Gabel (2012). “Interaction of dodecaborate cluster compounds on hydrophilic column materials in water.” Journal of Chromatography A 1256(0): 98-104.
Himmelspach, A., M. Finze, A. Vöge and D. Gabel (2012). “Cesium and Tetrabutylammonium Salt of the Ethynyl-closo-dodecaborate Dianion.” Zeitschrift für anorganische und allgemeine Chemie 638(3-4): 512-519.
Karki, K., D. Gabel and D. Roccatano (2012). “Structure and dynamics of dodecaborate clusters in water.” Inorganic Chemistry 51(9): 4894-4896.
Vöge, A. and D. Gabel (2012). Boron derivatives for application in nonlinear optics. Boron Science. New Technologies and Applications, CRC Press: 295-318.
Vöge, A. and D. Gabel (2012). Boron in weakly coordinating ions and ionic liquids. Boron Science. New Technologies and Applications, CRC Press: 807-826.
P. Farras, N. Vankova, L.L. Zeonjuk, J. Warneke, T. Dulcks, T. Heine, C. Vinas, F. Teixidor and D. Gabel(2012) From an icosahedron to a plane: flattening dodecaiodo-dodecaborate by successive stripping of iodine, Chemistry, 18: 13208-13212.
Warneke, J., Dülcks, T., Knapp, C. and Gabel, D. (2011) Collision-induced gas-phase reactions of perhalogenated closo-dodecaborate clusters – a comparative study. Phys. Chem. Chem. Phys. 13, 5712–5721
Mebs, S., Kalinowski, R., Grabowsky, S., Förster, D., Kickbusch, R., Justus, E., Morgenroth, W., Paulmann, C., Luger, P., Gabel, D. and Lentz, D. (2011) Charge Transfer via the Dative N- B Bond and Dihydrogen Contacts. Experimental and Theoretical Electron Density Studies of Four Deltahedral Boranes. Journal of Physical Chemistry A 115, 1385-1395.
Awad, D., Schrader, I., Bartok, M., Mohr, A. and Gabel, D. (2011) Comparative toxicology of trypan blue, brilliant blue G, and their combination together with polyethylene glycol on human pigment epithelial cells. Investigative Ophthalmology Visual Science 52, 4085-90.
Schütz, C., Brochhausen, C., Altieri, S., Bartholomew, K., Bortolussi, S., Enzmann, F., Gabel, D., Hampel, G., Kirkpatrick, C.J., Kratz, J.V., Minouchehr, S., Schmidberger, H. and Otto, G. (2011) Boron Determination in Liver Tissue by Combining Quantitative Neutron Capture Radiography (QNCR) and Histological Analysis for BNCT Treatment Planning at the TRIGA Mainz. Radiat Res 176, 388-96
Dr. Bohumir Grüner, Institute for Inorganic Chemistry, Czech Academy of Science: Recognition of chiral boron clusters
Prof. Dr. Werner Nau, Dr. Khaleel Assaf, Jacobs University Bremen: Supramolecular chemistry of boron clusters
Collaboration in 2011/2012:
Prof. Dr. Wolfgang Weigand, University of Jena: Iron-sulfur clusters
Prof. Dr. Rolf Schubert, Prof. Dr. Regine Süss, University of Freiburg: Cellular fate of boron lipids
Prof. Dr. Clara Viñas, Prof. Dr. Francesc Teixidor, Institute for Materials, CSIC, Barcelona: Quantum chemical calculations of boron clusters
Prof. Dr. Thomas Heine, Jacobs University: Quantum chemical calculations of boron clusters
Prof. Dr. Danilo Roccatano, Jacobs University: Molecular dynamics of aqueous solutions of boron clusters
Prof. Dr. Katarina Edwards, University of Uppsala: Chromatography of boron clusters
Dr. Thomas Dülcks, University of Bremen: Mass spectrometry of boron clusters