Publications by authors named "Jana Hildebrandt"

9 Publications

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Automated Quantum Dots Purification via Solid Phase Extraction.

Nanomaterials (Basel) 2022 Jun 9;12(12). Epub 2022 Jun 9.

Fraunhofer Institute for Microengineering and Microsystems IMM, 55129 Mainz, Germany.

The separation of colloidal nanocrystals from their original synthesis medium is an essential process step towards their application, however, the costs on a preparative scale are still a constraint. A new combination of approaches for the purification of hydrophobic Quantum Dots is presented, resulting in an efficient scalable process in regard to time and solvent consumption, using common laboratory equipment and low-cost materials. The procedure is based on a combination of solvent-induced adhesion and solid phase extraction. The platform allows the transition from manual handling towards automation, yielding an overall purification performance similar to one conventional batch precipitation/centrifugation step, which was investigated by thermogravimetry and gas chromatography. The distinct miscibility gaps between surfactants used as nanoparticle capping agents, original and extraction medium are clarified by their phase diagrams, which confirmed the outcome of the flow chemistry process. Furthermore, the solubility behavior of the Quantum Dots is put into context with the Hansen solubility parameters framework to reasonably decide upon appropriate solvent types.
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http://dx.doi.org/10.3390/nano12121983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230973PMC
June 2022

Novel Nickel(II), Palladium(II), and Platinum(II) Complexes with , Bidendate Cinnamic Acid Ester Derivatives: An In Vitro Cytotoxic Comparison to Ruthenium(II) and Osmium(II) Analogues.

Int J Mol Sci 2022 Jun 15;23(12). Epub 2022 Jun 15.

Institut für Anorganische und Analytische Chemie Friedrich-Schiller Universität Jena, Humboldtstraße 8, 07743 Jena, Germany.

(1) Background: Since the discovery of cisplatin's cytotoxic properties, platinum(II) compounds have attracted much interest in the field of anticancer drug development. Over the last few years, classical structure-activity relationships (SAR) have been broken by some promising new compounds based on platinum or other metals. We focus on the synthesis and characterization of 17 different complexes with β-hydroxydithiocinnamic acid esters as , bidendate ligands for nickel(II), palladium(II), and platinum(II) complexes. (2) Methods: The bidendate compounds were synthesized and characterized using classical methods including NMR spectroscopy, MS spectrometry, elemental analysis, and X-ray crystallography, and their cytotoxic potential was assessed using in vitro cell culture assays. Data were compared with other recently reported platinum(II), ruthenium(II), and osmium(II) complexes based on the same main ligand system. (3) Results: SAR analyses regarding the metal ion (M), and the alkyl-chain position (P) and length (L), revealed the following order of the effect strength for in vitro activity: M > P > L. The highest activities have Pd complexes and ortho-substituted compounds. Specific palladium(II) complexes show lower IC values compared to cisplatin, are able to elude cisplatin resistance mechanisms, and show a higher cancer cell specificity. (4) Conclusion: A promising new palladium(II) candidate (Pd3) should be evaluated in further studies using in vivo model systems, and the identified SARs may help to target platinum-resistant tumors.
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http://dx.doi.org/10.3390/ijms23126669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224311PMC
June 2022

Highly Cytotoxic Osmium(II) Compounds and Their Ruthenium(II) Analogues Targeting Ovarian Carcinoma Cell Lines and Evading Cisplatin Resistance Mechanisms.

Int J Mol Sci 2022 Apr 29;23(9). Epub 2022 Apr 29.

Institut für Anorganische und Analytische Chemie Friedrich-Schiller Universität Jena, Humboldtstraße 8, 07743 Jena, Germany.

(1) Background: Ruthenium and osmium complexes attract increasing interest as next generation anticancer drugs. Focusing on structure-activity-relationships of this class of compounds, we report on 17 different ruthenium(II) complexes and four promising osmium(II) analogues with cinnamic acid derivatives as O,S bidentate ligands. The aim of this study was to determine the anticancer activity and the ability to evade platin resistance mechanisms for these compounds. (2) Methods: Structural characterizations and stability determinations have been carried out with standard techniques, including NMR spectroscopy and X-ray crystallography. All complexes and single ligands have been tested for cytotoxic activity on two ovarian cancer cell lines (A2780, SKOV3) and their cisplatin-resistant isogenic cell cultures, a lung carcinoma cell line (A549) as well as selected compounds on three non-cancerous cell cultures in vitro. FACS analyses and histone γH2AX staining were carried out for cell cycle distribution and cell death or DNA damage analyses, respectively. (3) Results: IC50 values show promising results, specifically a high cancer selective cytotoxicity and evasion of resistance mechanisms for Ru(II) and Os(II) compounds. Histone γH2AX foci and FACS experiments validated the high cytotoxicity but revealed diminished DNA damage-inducing activity and an absence of cell cycle disturbance thus pointing to another mode of action. (4) Conclusion: Ru(II) and Os(II) compounds with O,S-bidentate ligands show high cytotoxicity without strong effects on DNA damage and cell cycle, and this seems to be the basis to circumvent resistance mechanisms and for the high cancer cell specificity.
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http://dx.doi.org/10.3390/ijms23094976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102668PMC
April 2022

Synthesis, characterization and biological investigation of platinum(ii) complexes with asparagusic acid derivatives as ligands.

Dalton Trans 2019 Jan;48(3):936-944

Institut für Anorganische und Analytische Chemie Friedrich-Schiller-Universität Jena, Humboldstraße 8, 07743 Jena, Germany.

After more than 50 years of platinum-based anticancer research only three compounds are in clinical use worldwide. The use of the well-known lead compound of this class of anticancer agents, cisplatin, is limited by its side effects and varying resistance mechanisms. Therefore, we report on platinum(ii) compounds with asparagusic acid derivatives as ligands which show interesting anticancer results on cisplatin resistant cell lines.
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http://dx.doi.org/10.1039/c8dt02553cDOI Listing
January 2019

Diselenolane-mediated cellular uptake.

Chem Sci 2018 Feb 17;9(7):1860-1866. Epub 2018 Jan 17.

Department of Organic Chemistry , University of Geneva , Geneva , Switzerland . Email: ; http://www.unige.ch/sciences/chiorg/matile/ ; Tel: +41 22 379 6523.

The emerging power of thiol-mediated uptake with strained disulfides called for a move from sulfur to selenium. We report that according to results with fluorescent model substrates, cellular uptake with 1,2-diselenolanes exceeds uptake with 1,2-dithiolanes and epidithiodiketopiperazines with regard to efficiency as well as intracellular localization. The diselenide analog of lipoic acid performs best. This 1,2-diselenolane delivers fluorophores efficiently to the cytosol of HeLa Kyoto cells, without detectable endosomal capture as with 1,2-dithiolanes or dominant escape into the nucleus as with epidithiodiketopiperazines. Diselenolane-mediated cytosolic delivery is non-toxic (MTT assay), sensitive to temperature but insensitive to inhibitors of endocytosis (chlorpromazine, methyl-β-cyclodextrin, wortmannin, cytochalasin B) and conventional thiol-mediated uptake (Ellman's reagent), and to serum. Selenophilicity, the extreme CSeSeC dihedral angle of 0° and the high but different acidity of primary and secondary selenols might all contribute to uptake. Thiol-exchange affinity chromatography is introduced as operational mimic of thiol-mediated uptake that provides, in combination with rate enhancement of DTT oxidation, direct experimental evidence for existence and nature of the involved selenosulfides.
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http://dx.doi.org/10.1039/c7sc05151dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892345PMC
February 2018

Platinum(ii) O,S complexes as potential metallodrugs against Cisplatin resistance.

Dalton Trans 2016 Nov;45(47):18876-18891

Institut für Anorganische und Analytische Chemie Friedrich-Schiller-Universität Jena Humboldtstraße 8, 07743 Jena, Germany.

We report on platinum(ii) complexes with different cinnamic acid derivatives as ligands with cytotoxic activity against Cisplatin resistant ovarian cancer cell line subcultures of SKOV3 and A2780. A typical mechanism of action for platinum(ii) complexes as Cisplatin itself is binding to the DNA and inducing double-strand breaks. We examined the biological behavior of these potential drugs with 9-methylguanine using NMR spectroscopic methods and their DNA damage potential including γH2AX-foci analyses. X-ray diffraction methods have been used to elucidate the molecular structures of the platinum(ii) complexes. Interactions with the model protein lysozyme have been evaluated by different techniques including UV-Vis absorption spectroscopy, fluorescence and X-ray crystallography.
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http://dx.doi.org/10.1039/c6dt01388kDOI Listing
November 2016

Unusual mode of protein binding by a cytotoxic π-arene ruthenium(ii) piano-stool compound containing an O,S-chelating ligand.

Dalton Trans 2016 Aug;45(31):12283-7

Department of Chemical Sciences, University of Naples Federico II, Italy. and Institute of Biostructures and Bioimages, Naples, Italy.

A new pseudo-octahedral π-arene ruthenium(ii) piano-stool compound, containing an O,S-bidentate ligand (compound 1) and showing significant cytotoxic activity in vitro, was synthesized and characterized. In solution stability and interaction with the model protein bovine pancreatic ribonuclease (RNase A) were investigated by using UV-Vis absorption spectroscopy. Its crystal structure and that of the adduct formed upon reaction with RNase A were obtained by X-ray crystallography. The comparison between the structure of purified compound 1 and that of the fragment bound to RNase A reveals an unusual mode of protein binding that includes ligand exchange and alteration of coordination sphere geometry.
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http://dx.doi.org/10.1039/c6dt02380kDOI Listing
August 2016

Platinum(II) Complexes with O,S Bidentate Ligands: Biophysical Characterization, Antiproliferative Activity, and Crystallographic Evidence of Protein Binding.

Inorg Chem 2015 Sep 17;54(17):8560-70. Epub 2015 Aug 17.

Institute of Inorganic and Analytical Chemistry, Friedrich-Schiller-University Jena , Humboldtstraße 8, 07743 Jena, Germany.

We recently characterized a series of novel platinum(II) compounds bearing a conserved O,S binding moiety as a bifunctional ligand and evaluated their solution behavior and antiproliferative properties in vitro against a representative cancer cell line. On the whole, those platinum compounds showed an appreciable stability in mixed dimethyl sulfoxide-aqueous buffers and promising in vitro cytotoxic effects; yet they manifested a rather limited solubility in aqueous media making them poorly suitable for further pharmaceutical development. To overcome this drawback, four new derivatives of this series were prepared and characterized based on a careful choice of substituents on the O,S bidentate ligand. The solubility and stability profile of these novel compounds in a reference buffer was determined, as well as the ligands' log P(o/w) value (P(o/w) = n-octanol-water partition coefficient) as an indirect measure for the complexes' lipophilicity. The antiproliferative properties were comparatively evaluated in a panel of three cancer cell lines. The protein binding properties of the four platinum compounds were assessed using the model protein hen egg white lysozyme (HEWL), and the molecular structures of two relevant HEWL-metallodrug adducts were solved. Overall, it is shown that a proper choice of the substituents leads to a higher solubility and enables a selective fine-tuning of the antiproliferative properties. The implications of these results are thoroughly discussed.
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http://dx.doi.org/10.1021/acs.inorgchem.5b01238DOI Listing
September 2015

Making nonsymmetrical bricks: synthesis of insoluble dipolar sexiphenyls.

Org Lett 2014 Jun 14;16(11):2838-41. Epub 2014 May 14.

Department of Chemistry & IRIS Adlershof, Humboldt-Universität zu Berlin , Brook-Taylor-Strasse 2, 12489 Berlin, Germany.

A versatile synthesis of nonsymmetrical, terminally substituted p-sexiphenyl (6P) derivatives has been developed. The synthesis makes use of a nonsymmetrical starting material as well as modular functionalization using Suzuki cross-coupling to yield a soluble precursor, which finally is converted to the insoluble target 6P derivatives. These derivatives display similar electronic and optical properties to the parent 6P, yet the permanent dipole along their molecular axis allows for tuning of their self-assembly on various substrate surfaces.
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http://dx.doi.org/10.1021/ol5009087DOI Listing
June 2014
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