Publications by authors named "Dana Kaizerman-Kane"

4 Publications

  • Page 1 of 1

Design Guidelines for Cationic Pillar[n]arenes that Prevent Biofilm Formation by Gram-Positive Pathogens.

ACS Infect Dis 2021 03 3;7(3):579-585. Epub 2021 Mar 3.

School of Chemistry, Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.

Bacterial biofilms are a major threat to human health, causing persistent infections that lead to millions of fatalities worldwide every year. Biofilms also cause billions of dollars of damage annually by interfering with industrial processes. Recently, cationic pillararenes were found to be potent inhibitors of biofilm formation in Gram-positive bacteria. To identify the structural features of pillararenes that result in antibiofilm activity, we evaluated the activity of 16 cationic pillar[5]arene derivatives including that of the first cationic water-soluble pillar[5]arene-based rotaxane. Twelve of the derivatives were potent inhibitors of biofilm formation by Gram-positive pathogens. Structure activity analyses of our pillararene derivatives indicated that positively charged head groups are critical for the observed antibiofilm activity. Although certain changes in the lipophilicity of the substituents on the positively charged head groups are tolerated, dramatic elevation in the hydrophobicity of the substituents or an increase in steric bulk on these positive charges abolishes the antibiofilm activity. An increase in the overall positive charge from 10 to 20 did not affect the activity significantly, but pillararenes with 5 positive charges and 5 long alkyl chains had reduced activity. Surprisingly, the cavity of the pillar[n]arene is not essential for the observed activity, although the macrocyclic structure of the pillar[n]arene core, which facilitates the clustering of the positive charges, appears important. Interestingly, the compounds found to be efficient inhibitors of biofilm formation were nonhemolytic at concentrations that are ∼100-fold of their MBIC (the minimal concentration of a compound at which at least 50% inhibition of biofilm formation was observed compared to untreated cells). The structure-activity relationship guidelines established here pave the way for a rational design of potent cationic pillar[n]arene-based antibiofilm agents.
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http://dx.doi.org/10.1021/acsinfecdis.0c00662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041275PMC
March 2021

Temperature-Dependent and pH-Responsive Pillar[5]arene-Based Complexes and Hydrogen-Bond-Based Supramolecular Pentagonal Boxes in Water.

Chemistry 2020 Sep 10;26(49):11250-11255. Epub 2020 Aug 10.

School of Chemistry, Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel.

Supramolecular systems in water are of paramount importance and those based on hydrogen bonds are both intriguing and scarce. Here, after studying the peculiar host-guest complexes formed between per-dimethylamino-pillar[5]arene (1) and the bis-sulfonates 2 a-c, we describe the formation of the first hydrogen-bond-based supramolecular pentagonal boxes (SPBs), which are stable in water. These pH-responsive SPBs are constructed from 1 as a body, benzene polycarboxylic acids 3 a,b as lid compounds, and 2 a-c as guests. We demonstrate that encapsulation of 2 a-c in pillar[5]arene 1 and in the highly stable water-soluble SPBs, that is, 1(3 a) and 1(3 b) , is both temperature and pH dependent and, quite interestingly, depends, on the nature of the lid compounds used for capping the boxes even at high pH. We also highlight the difference in the H NMR characteristics of 2 b and 2 c in the cavity of 1 and the SPBs.
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http://dx.doi.org/10.1002/chem.202000972DOI Listing
September 2020

pH-Responsive Pillar[6]arene-based Water-Soluble Supramolecular Hexagonal Boxes.

Angew Chem Int Ed Engl 2019 Apr 14;58(16):5302-5306. Epub 2019 Mar 14.

School of Chemistry, Sackler Faculty of Exact sciences, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel.

We describe the preparation of the first water-soluble pH-responsive supramolecular hexagonal boxes (SHBs) based on multiple charge-assisted hydrogen bonds between peramino-pillar[6]arenes 2 with the molecular "lid" mellitic acid (1 a). The interaction between 2 and 1 a, as well as the other "lids" pyromellitic and trimesic acids (1 b and 1 c, respecively) were studied by a combination of experimental and computational methods. Interestingly, the addition of 1 a to the complexes of the protonated form of pillar[6]arene 2, that is, 3, with bis-sulfonate 4 a or 4 b, immediately led to guest escape along with the formation of closed 1 a 2 supramolecular boxes. Moreover, the process of the openning and closing of the supramolecular boxes along with threading and escaping of the guests, respectively, was found to be reversible and pH-responsive. This study paves the way for the easy and modular preparation of different SHBs that may have myriad applications.
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http://dx.doi.org/10.1002/anie.201900217DOI Listing
April 2019

High Exchange Rate Complexes of Xe with Water-Soluble Pillar[5]arenes for Adjustable Magnetization Transfer MRI.

Chemphyschem 2019 01 21;20(2):246-251. Epub 2018 Aug 21.

Molecular Imaging, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Str. 10, 13125, Berlin, Germany.

Macrocyclic host structures for generating transiently bound Xe have been used in various ultra-sensitive NMR and MRI applications for molecular sensing of biochemical analytes. They are based on hyperpolarized nuclei chemical exchange saturation transfer (Hyper-CEST). Here, we tested a set of water-soluble pillar[5]arenes with different counterions in order to compare their potential contrast agent abilities with that of cryptophane-A (CrA), the most widely used host for such purposes. The exchange of Xe with such compounds was found to be sensitive to the type of ions present in solution and can be used for switchable magnetization transfer (MT) contrast that arises from off-resonant pre-saturation. We demonstrate that the adjustable MT magnitude depends on the interplay of saturation parameters and found that the optimum MT contrast surpasses the CrA CEST performance at moderate saturation power. Since modification of such water-soluble pillar[5]arenes is straightforward, these compounds can be considered a promising platform for designing various sensors that may complement the field of Xe HyperCEST-based biosensing MRI.
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http://dx.doi.org/10.1002/cphc.201800618DOI Listing
January 2019