Jeffery T Davis

Loyola University Maryland, Baltimore, Maryland, United States

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Publications (74)567.7 Total impact

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    ABSTRACT: The ability to modulate the physical properties of a supramolecular hydrogel may be beneficial for biomaterial and biomedical applications. We find that guanosine (G 1), when combined with 0.5 equiv of potassium borate, forms a strong, self-supporting hydrogel with elastic moduli > 10 kPa. The counter-cation in the borate salt (MB(OH)4) significantly alters the physical properties of the hydrogel. The gelator combination of G 1 and KB(OH)4 formed the strongest hydrogel, while the weakest system was obtained with LiB(OH)4, as judged by 1H NMR and rheology. Data from powder XRD, 1H double-quantum solid-state magic-angle spinning (MAS) NMR and small-angle neutron scattering (SANS) were consistent with a structural model that involves formation of borate dimers and G4•K+ quartets by G 1 and KB(OH)4. Stacking of these G4•M+ quartets into G4-nanowires gives a hydrogel. We found that the M+ cation helps stabilize the anionic guanosine-borate (GB) diesters, as well as the G4-quartets. Supplementing the standard gelator mixture of G 1 and 0.5 equiv of KB(OH)4 with additional KCl or KNO3 increased the strength of the hydrogel. We found that thioflavin T fluoresces in the presence of G4•M+ precursor structures. This fluorescence response for thioflavin T was the greatest for the K+ GB system, presumably due to the enhanced interaction of the dye with the more stable G4•K+ quartets. The fluorescence of thioflavin T increased as a function of gelator concentration with an increase that correlated with the system's gel point, as measured by solution viscosity.
    Journal of the American Chemical Society 04/2015; 137(17). DOI:10.1021/jacs.5b02753 · 11.44 Impact Factor
  • Jeffery T Davis
    Nature Chemistry 09/2014; 6(10):852-3. DOI:10.1038/nchem.2072 · 23.30 Impact Factor
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    ABSTRACT: Supramolecular hydrogels derived from natural products have promising applications in diagnostics, drug delivery and tissue engineering. We studied formation of a long-lived hydrogel made by mixing guanosine (G 1) with 0.5 equiv of KB(OH)4. This ratio of borate anion to ligand is crucial for gelation as it links two molecules of G 1, which facilitates cation-templated assembly of G4•K+-quartets. The guanosine-borate (GB) hydrogel, characterized by cryo-TEM, CD and 11B MAS NMR, is stable in water that contains physio-logically relevant concentrations of K+. Further, non-covalent interactions, such as electrostatics and π-stacking and hy-drogen bonding, enable incorporation of a cationic dye and nucleosides into the GB hydrogel.
    Journal of the American Chemical Society 08/2014; 136(36). DOI:10.1021/ja507506c · 11.44 Impact Factor
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    ABSTRACT: Prodigiosin is the parent compound of the tripyrrolic natural products known as the prodigiosenes. Some of these natural products and their synthetic analogs show anti-cancer, immunosuppressive and antimicrobial actions, amongst other biological activities. One mechanism put forth to explain their biological activity is that since prodigiosenes are typically protonated at physiological pH they can alter intracellular pH via HCl co-transport (or Cl−/OH− exchange) across cell membranes. In this study we synthesized a series of prodigiosene analogs with different –O-aryl substituents attached to the B-ring of the tripyrrolic skeleton. NMR studies showed that these analogs can exist as a mixture of two stable α and β conformers in acidic solution, and that both conformers can bind anions in solution. We found that the electronic nature of the O-aryl substituent on the B-ring influences the rate at which these prodigiosenes catalyze transmembrane anion transport, i.e. the prodigiosenes with the higher pKa had greater Cl−/NO3− exchange rates. Four of the synthetic prodigiosenes were tested for their in vitro anti-cancer activities in the NCI60 human tumour panel. Despite their promising in vitro anti-cancer activity (GI50 values ranging from 18 to 74 nM), there was no evidence that this activity is influenced by the extent of protonation of these synthetic prodigiosenes.
    Organic & Biomolecular Chemistry 08/2014; 12(38). DOI:10.1039/C4OB01399A · 3.49 Impact Factor
  • Gretchen Marie Peters, Jeffery T. Davis
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    ABSTRACT: Nucleoside analogues are used as drugs. Due to their hydrophilicity, nucleosides are poorly permeable to membranes and transporter proteins are required for efficient uptake. One approach towards improving membrane permeability of nucleosides is to use synthetic transporters. We describe ways to control transport of nucleosides across a liquid membrane. Hexanoylguanosine 1 selectively extracts and transports cytidines across a CHCl3 membrane. Transport catalysed by G 1 was influenced by the nucleoside's sugar, with a selectivity of dC 4 > rC 3 > araC 5. Selective transport could be modulated by adding compounds to the aqueous source phase or to the organic phase. Addition of K+2,6-DNP–8 to CHCl3 containing G 1 switched off transport of rC 3 and dC 4 due to formation of a G-quartet assembly. A lipophilic G 1·C 2 base pair could not transport dC 4, but did catalyse transport of dG 7 across the CHCl3 barrier. We propose that transport occurs because of formation of a base triple G 1·C 2·dG 7. Addition of Na2B4O79 to a source phase containing rC 3, dC 4 and araC 5 shuts down transport of rC 3 by G 1, due to formation of borate esters. These results indicate that one can control the selective transport of nucleosides.
    Supramolecular Chemistry 04/2014; 26(3-4). DOI:10.1080/10610278.2013.872782 · 2.13 Impact Factor
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    ABSTRACT: Analogues of the tripyrrolic natural product prodigiosin bearing an additional methyl and a carbonyl group at the C-ring were synthesised and evaluated. In vitro anticancer activity screening (NCI) and the study of modes of action (copper-mediated cleavage of double-stranded DNA and transmembrane transport of chloride anions) showed that the presence of the methyl group is not detrimental to activity. Furthermore, although the presence of an ester conjugated to the prodigiosene C-ring seems to decrease both pKa and chloride transport efficiency compared to the natural product, these analogues still exhibit a high rate of chloride transport. All analogues exhibit good in vitro anticancer activity and reduced toxicity compared to the natural product: compare an acute systemic toxicity of 100 mg kg(-1) in mice vs. 4 mg kg(-1) for prodigiosin, pointing towards a larger therapeutic window than for the natural product.
    Organic & Biomolecular Chemistry 05/2013; 11(23). DOI:10.1039/c3ob40477c · 3.49 Impact Factor
  • Soheila Bahmanjah, Ning Zhang, Jeffery T Davis
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    ABSTRACT: We report that the amphiphilic natural product, monoacylglycerol 1, functions as a transmembrane Cl(-)/NO(3)(-) anion transporter. The 1,2-diol group is crucial for the transport function since diacylglycerol and triacylglycerol analogs are not anion transporters. Furthermore, adding another hydrogen bond donor to the glycerol head-group and perfluorination of the acyl tail gave synthetic analogs with improved Cl(-) membrane transport properties.
    Chemical Communications 03/2012; 48(37):4432-4. DOI:10.1039/c2cc18148g · 6.72 Impact Factor
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    ABSTRACT: We report the first implementation of the multiple-quantum magic-angle-spinning method to obtain high-resolution (39)K NMR spectra for bio-organic solids. The observed spectral resolution in the isotropic dimension is nearly at the sub-ppm level, which approaches the intrinsic resolution limit determined primarily by quadrupole relaxation. We show that high-resolution solid-state (39)K NMR spectroscopy can be used as a new means of probing K(+) ions in biomolecular systems.
    Journal of the American Chemical Society 08/2011; 133(49):19570-3. DOI:10.1021/ja2052446 · 11.44 Impact Factor
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    ABSTRACT: A new series of structurally simple compounds containing thiourea groups have been shown by a combination of ion-selective electrode and (13)C NMR techniques to be potent chloride-bicarbonate exchange agents that function at low concentration in POPC and POPC/cholesterol membranes.
    Chemical Science 02/2011; 2(2-2):256-260. DOI:10.1039/C0SC00503G · 8.60 Impact Factor
  • Jeffery T Davis, Oluyomi Okunola, Roberto Quesada
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    ABSTRACT: Anions cannot diffuse passively through biological membranes and membrane-bound proteins mainly govern the transmembrane movement of these charged species. The use of synthetic compounds that are able to facilitate the transmembrane transport of anions is a fascinating and burgeoning topic. The study of facilitated anion transport across lipid bilayers is an emerging field in supramolecular and bioorganic chemistry. In this critical review we describe the recent research progress in this area, focusing on literature published during the years 2007-2009. An overview of the assays that are used in the transmembrane transport of anions is also included (158 references).
    Chemical Society Reviews 10/2010; 39(10):3843-62. DOI:10.1039/b926164h · 30.43 Impact Factor
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    ABSTRACT: Easy-to-make tripodal tris-thiourea receptors based upon tris(2-aminoethyl)amine are capable of chloride/bicarbonate transport and as such represent a new class of bicarbonate transport agent.
    Chemical Communications 09/2010; 46(34):6252-4. DOI:10.1039/c0cc01684e · 6.72 Impact Factor
  • Jeffery T Davis
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    ABSTRACT: A systematic study that combines both theory and experiment now provides direct evidence for the existence of anion-pi interactions in compounds that facilitate the transport of anions across phospholipid membranes. This study offers new insight into the factors that affect the strength, selectivity and functional relevance of anion-pi interactions.
    Nature Chemistry 07/2010; 2(7):516-7. DOI:10.1038/nchem.723 · 23.30 Impact Factor
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    ABSTRACT: The sphingolipid, ceramide 1, facilitates transport of Cl(-) and HCO(3)(-) anions across lipid bilayers under conditions where large transmembrane pores are not formed. Ceramide's 1,3-diol unit is essential for both binding and transporting these anions.
    Chemical Communications 06/2010; 46(22):3950-2. DOI:10.1039/c0cc00493f · 6.72 Impact Factor
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 04/2010; 33(17). DOI:10.1002/chin.200217061
  • [Show abstract] [Hide abstract]
    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 03/2010; 30(10). DOI:10.1002/chin.199910223
  • Jeffery T. Davis
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    ABSTRACT: Abstract The red-colored prodiginines, exemplified by prodigiosin 1, are secondary metabolites produced by a number of microorganisms, including the bacterium Serratia marcescens. These tripyrrole natural products and their synthetic analogs have received renewed attention over the past deacade, primarily because of their promising immunosuppressive and anticancer activities. One of the hallmarks of prodiginin chemistry is the ability of the monoprotonated ligand to bind anions, including the essential chloride and bicarbonate ions. The resulting lipophilic ion pair is then able to diffuse across the hydrophobic barrier presented by phospholipid bilayers. Thus, prodiginines have been found to be potent transmembrane anion transporters and HCl cotransporters. In this chapter, the author reviews what is known about the solid-state structure of prodiginins and their anion complexes, the solution conformation of prodiginines, and the biochemcal evidence for the ability to bind anions and to transport HCl across cell membranes. Recent progress in making synthetic models of prodiginines and recent results on the ability of prodigiosin to transport HCO 3 − across lipid membranes are discussed. Graphical Abstract
  • Jeffery T. Davis
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    ABSTRACT: Synthetic ion channels and pores not only represent models of natural transmembrane ion channels, but also have potential applications in the areas of drug delivery, biosensors, antimicrobial agents and other molecular devices. In this presentation, synthetic derivatives of natural products that combine both molecular recognition and membrane soluble features are utilized for the development of synthetic ion channels. Progress in this area of using various natural products, such as nucleosides, bile acids, sphingolipids and prodigiosins as transmembrane transporters of ions and small molecules will be discussed.
    61st American Chemical Society Southeast Regional Meeting; 10/2009
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    Ling Ma, William A Harrell, Jeffery T Davis
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    ABSTRACT: The use of a bis-urea lithocholamide linker within a guanosine-sterol dimer resulted in formation of large and stable ion channels. The channels were longer-lived than those formed by the corresponding bis-carbamate.
    Organic Letters 05/2009; 11(7):1599-602. DOI:10.1021/ol9002477 · 6.32 Impact Factor
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    ABSTRACT: Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl(-)/HCO(3)(-) exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems.
    Nature Chemistry 05/2009; 1(2):138-44. DOI:10.1038/nchem.178 · 23.30 Impact Factor
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    ABSTRACT: Using solid-state (23)Na NMR and quantum chemical calculations we have found that the Na(+) ion bound to a calix[4]arene-guanosine conjugate dimer resides slightly above the G-quartet plane and simultaneously coordinates to a water molecule in a square-pyramidal (penta-coordination) geometry.
    Chemical Communications 05/2009; DOI:10.1039/b900442d · 6.72 Impact Factor

Publication Stats

3k Citations
567.70 Total Impact Points

Institutions

  • 1997–2014
    • Loyola University Maryland
      • Department of Chemistry
      Baltimore, Maryland, United States
  • 1995–2014
    • University of Maryland, College Park
      • Department of Chemistry and Biochemistry
      Maryland, United States
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2005
    • Universiteit Twente
      • Institute for Nanotechnology (MESA+)
      Enschede, Overijssel, Netherlands
  • 2003
    • Queen's University
      • Department of Chemistry
      Kingston, Ontario, Canada
  • 2000
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy