Matthew J Panzner

University of Akron, Akron, Ohio, United States

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Publications (53)205.03 Total impact

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    ABSTRACT: Mercury(II) metallation of Pseudomonas aeruginosa azurin has been characterized structurally and biochemically. The X-ray crystal structure at 1.5Å of mercury(II) metallated azurin confirms the coordination of mercury at the copper binding active site and a second surface site. These findings are further validated by NMR, Matrix-assisted laser desorption/ionization spectrometry (MALDI), and UV-visible spectroscopic methods indicating copper displacement from the wild-type protein. Bioinformatic analysis has identified homologous human protein domains computationally, and compared them to the structure of azurin, providing a model for human mercury interactions. Study of the mercury-azurin adduct, in combination with other known examples of protein-heavy metal interactions, could provide further insight into the chemical mechanisms of toxicological interactions, leading toward a global understanding of the biological speciation of toxic heavy metals.
    Journal of inorganic biochemistry. 09/2014; 141C:152-160.
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    ABSTRACT: A hydroxybenzohydrazide-based Schiff base ligand was conveniently synthesized. Upon addition of Zn(2+) cations, the ligand exhibited a high tendency to form a binuclear structure with a 2 : 2 ligand-to-zinc ratio, which was accompanied by a large fluorescence turn-on (λem = 507 nm, ϕfl ≈ 0.28). The reactivity of the zinc complex was examined using different phosphate anions, which reveals a higher response to acid pyrophosphate anions. Detailed spectroscopic studies show that the pyrophosphate response is based on the ligand displacement mechanism.
    Dalton Transactions 08/2014; · 3.81 Impact Factor
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    ABSTRACT: Medium-sized cyclic oligomeric phosphazenes [PCl2N]m (where m = 5-9) that were prepared from the reaction of PCl5 and NH4Cl in refluxing chlorobenzene have been isolated by a combination of sublimation/extraction and column chromatography from the predominant products [PCl2N]3 and [PCl2N]4. The medium-sized rings [PCl2N]m have been characterized by electrospray ionization-mass spectroscopy (ESI-MS), their (31)P chemical shifts have been reassigned, and their T1 relaxation times have been obtained. Crystallographic data has been recollected for [PCl2N]5, and the crystal structures of [PCl2N]6, and [PCl2N]8 are reported. Halogen-bonding interactions were observed in all the crystal structures of cyclic [PCl2N]m (m = 3-5, 6, 8). The crystal structures of [P(OPh)2N]7 and [P(OPh)2N]8, which are derivatives of the respective [PCl2N]m, are also reported. Comparisons of the intermolecular forces and torsion angles of [PCl2N]8 and [P(OPh)2N]8 with those of three other octameric rings are described. The comparisons show that chlorophosphazenes should not be considered prototypical, in terms of solid-state structure, because of the strong influence of halogen bonding.
    Inorganic chemistry. 08/2014;
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    ABSTRACT: Multiple biophysical methods demonstrate that silver effectively metallates Pseudomonas aeruginosa apo-azurin in solution. X-ray crystallography of the silver-modified protein reveals that silver binds to azurin at the traditional copper mediated active site with nearly identical geometry. Cyclic voltammetry indicates that the silver adduct is redox inert. Our results suggest that a potential mechanism for the microbial toxicity of silver is the deactivation of copper oxidoreductases by the effective binding and structural mimicry by silver without the corresponding function.
    Journal of inorganic biochemistry 07/2013; 128C:11-16. · 3.25 Impact Factor
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    ABSTRACT: The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multi-functional, shell crosslinked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least two-to-four days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg Ag+ delivered over 5 doses at 12-hour intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence.
    ACS Nano 05/2013; · 12.03 Impact Factor
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    ABSTRACT: Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH(2)Cl(2) (organic):PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery.
    Molecular Pharmaceutics 10/2012; · 4.57 Impact Factor
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    ABSTRACT: Many anticancer drugs have been established clinically, but their efficacy can be compromised by nonspecific toxicity and an inability to reach the desired cancerous intracellular spaces. In order to address these issues, researchers have explored the use of folic acid as a targeted moiety to increase specificity of chemotherapeutic drugs. To expand upon such research, we have conjugated folic acid to functionalized poly(ethylene glycol) and subsequently decorated the surface of l-tyrosine polyphosphate (LTP) nanoparticles. These nanoparticles possess the appropriate size (100-500 nm) for internalization as shown by scanning electron microscopy and dynamic light scattering. Under simulated physiological flow, LTP nanoparticles decorated with folic acid (targeted nanoparticles) show a 10-fold greater attachment to HeLa, a cervical cancer cell line, compared to control nanoparticles and to human dermal fibroblasts. The attachment of these targeted nanoparticles progresses at a linear rate, and the strength of this nanoparticle attachment is shown to withstand shear stresses of 3.0 dyn/cm(2). These interactions of the targeted nanoparticles to HeLa are likely a result of a receptor-ligand binding, as a competition study with free folic acid inhibits the nanoparticle attachment. Finally, the targeted nanoparticles encapsulated with a silver based drug show increased efficacy in comparison to nondecorated (plain) nanoparticles and drug alone against HeLa cells. Thus, targeted nanoparticles are a promising delivery platform for developing anticancer therapies that overexpress the folate receptors (FRs).
    Molecular Pharmaceutics 09/2012; · 4.57 Impact Factor
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    ABSTRACT: We develop a mathematical model of nanoparticles depositing onto and penetrating into a biofilm grown in a parallel-plate flow cell. We carry out deposition experiments in a flow cell to support the modeling. The modeling and the experiments are motivated by the potential use of polymer nanoparticles as part of a treatment strategy for killing biofilms infecting the deep passages in the lungs. In the experiments and model, a fluid carrying polymer nanoparticles is injected into a parallel-plate flow cell in which a biofilm has grown over the bottom plate. The model consists of a system of transport equations describing the deposition and diffusion of nanoparticles. Standard asymptotic techniques that exploit the aspect ratio of the flow cell are applied to reduce the model to two coupled partial differential equations. We perform numerical simulations using the reduced model. We compare the experimental observations with the simulation results to estimate the nanoparticle sticking coefficient and the diffusion coefficient of the nanoparticles in the biofilm. The distributions of nanoparticles through the thickness of the biofilm are consistent with diffusive transport, and uniform distributions through the thickness are achieved in about four hours. Nanoparticle deposition does not appear to be strongly influenced by the flow rate in the cell for the low flow rates considered.
    Annals of Biomedical Engineering 08/2012; · 3.23 Impact Factor
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    ABSTRACT: Silver N-heterocyclic carbene complexes have been shown to have great potential as antimicrobial agents, affecting a wide spectrum of both Gram-positive and Gram-negative bacteria. A new series of three silver carbene complexes (SCCs) based on 4,5,6,7-tetrachlorobenzimidazole has been synthesized, characterized, and tested against a panel of clinical strains of bacteria. The imidazolium salts and their precursors were characterized by elemental analysis, mass spectrometry, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction. The silver carbene complexes, SCC32, SCC33, and SCC34 were characterized by elemental analysis, (1)H and (13)C NMR spectroscopy, and single crystal X-ray diffraction. These complexes proved highly efficacious with minimum inhibitory concentrations (MICs) ranging from 0.25 to 6 μg mL(-1). Overall, the complexes were effective against highly resistant bacteria strains, such as methicillin-resistant Staphylococcus aureus (MRSA), weaponizable bacteria, such as Yersinia pestis, and pathogens found within the lungs of cystic fibrosis patients, such as Pseudomonas aeruginosa, Alcaligenes xylosoxidans, and Burkholderia gladioli. SCC33 and SCC34 also showed clinically relevant activity against a silver-resistant strain of Escherichia coli based on MIC testing.
    Dalton Transactions 03/2012; 41(21):6500-6. · 3.81 Impact Factor
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    ABSTRACT: Open chain Cbz-L-aa(1)-L-Pro-Bt (Bt=benzotriazole) sequences were converted into either the corresponding trans- or cis-fused 2,5-diketopiperazines (DKPs) depending on the reaction conditions. Thermodynamic tandem cyclization/epimerization afforded selectively the corresponding trans-DKPs (69-75%). Complementarily, tandem deprotection/cyclization led to the cis-DKPs (65-72%). A representative set of proline-containing cis- and trans-DKPs has been prepared. A mechanistic investigation, based on chiral HPLC, kinetics, and computational studies enabled a rationalization of the results.
    Chemistry 02/2012; 18(9):2632-8. · 5.93 Impact Factor
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    ABSTRACT: A class of shape-persistent metallodendrimer has been developed through a self-assembly strategy, in which 〈tpy-RuII-tpy〉 or 〈tpy-FeII-tpy〉 connectivity is utilized, as branching moieties or nodes. These metallomacromolecules were fully characterized by 1H and 13C NMR, traveling wave ion mobility mass spectrometry (TWIM MS), single crystal X-ray, UV-vis absorption, photoluminescence, and cyclic voltammetry. Significant increase in the drift times of the same charge states was observed with increasing generation of these complexes, which is in line with the change of molecular size. Moreover, the photophysical properties (molar extinction coefficients) and electrochemical stability of the complexes were noticeably different depending on size and metal ion center.
    New Journal of Chemistry 01/2012; 36(2):484-491. · 2.97 Impact Factor
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    ABSTRACT: Silver carbenes may represent novel, broad-spectrum antimicrobial agents that have low toxicity while providing varying chemistry for targeted applications. Here, the bactericidal activity of four silver carbene complexes (SCCs) with different formulations, including nanoparticles (NPs) and micelles, was tested against a panel of clinical strains of bacteria and fungi that are the causative agents of many skin and soft tissue, respiratory, wound, blood, and nosocomial infections. MIC, MBC and multidose experiments were conducted against a broad range of bacteria and fungi. Time-release and cytotoxicity studies of the compounds were also carried out. Free SCCs and SCC NPs were tested against a panel of medically important pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter baumannii (MRAB), Pseudomonas aeruginosa, Burkholderia cepacia and Klebsiella pneumoniae. All four SCCs demonstrated strong efficacy in concentration ranges of 0.5-90 mg/L. Clinical bacterial isolates with high inherent resistance to purified compounds were more effectively treated either with an NP formulation of these compounds or by repeated dosing. Overall, the compounds were active against highly resistant bacterial strains, such as MRSA and MRAB, and were active against the biodefence pathogens Bacillus anthracis and Yersinia pestis. All of the medically important bacterial strains tested play a role in many different infectious diseases. The four SCCs described here, including their development as NP therapies, show great promise for treating a wide variety of bacterial and fungal pathogens that are not easily killed by routine antimicrobial agents.
    Journal of Antimicrobial Chemotherapy 01/2012; 67(1):138-48. · 5.34 Impact Factor
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    ABSTRACT: The X-ray crystal structure, NMR binding studies, and enzyme activity of silver(I) metallated hen egg white lysozyme are presented. Primary bonding of silver is observed through His15 with secondary bonding interactions coming from nearby Arg14 and Asp87. A covalently bound nitrate completes a four coordinate binding pocket.
    Chemical Communications 12/2011; 47(46):12479-81. · 6.38 Impact Factor
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    ABSTRACT: Ethane-sulfonic acid-based buffers like 2-[4-(2-hy-droxy-eth-yl)-piperazin-1-yl]ethane-sulfonic acid (HEPES) are commonly used in biological experiments because of their ability to act as non-coordinating ligands towards metal ions. However, recent work has shown that some of these buffers may in fact coordinate metal ions. The title complex, {[Ag(C(8)H(17)N(2)O(4)S)]·3H(2)O}(n), is a metal-organic framework formed from HEPES and a silver(I) ion. In this polymeric complex, each Ag atom is primarily coordinated by two N atoms in a distorted linear geometry. Weaker secondary bonding inter-actions from the hy-droxy and sulfate O atoms of HEPES complete a distorted seesaw geometry. The crystal structure is stabilized by O-H⋯O hydrogen-bonding interactions.
    Acta Crystallographica Section E Structure Reports Online 09/2011; 67(Pt 9):m1178-9. · 0.35 Impact Factor
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    ABSTRACT: Phosphazene polymers are classically synthesized by the high-temperature, ring-opening polymerization (ROP) of [PCl(2)N](3) to give [PCl(2)N](n), followed by functionalization of [PCl(2)N](n) with different side groups. We investigated the interactions of [PCl(2)N](3) with Lewis acids because Lewis acids have been used to induce the high-temperature ROP of [PCl(2)N](3). The reactions of [PCl(2)N](3) with MX(3) (M = group 13, X = halides), under strict anaerobic conditions gave adducts [PCl(2)N](3)·MX(3). Adducts were characterized by X-ray crystallography and multinuclear and variable-temperature NMR studies, and mechanistic understanding of their fluxional behavior in solution was achieved. The properties of the [PCl(2)N](3)·MX(3) adducts at or near room temperature strongly suggests that such adducts are not involved directly as intermediates in the high-temperature ROP of [PCl(2)N](3).
    Inorganic Chemistry 08/2011; 50(18):8937-45. · 4.59 Impact Factor
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    ABSTRACT: Chemotherapy employs toxic chemicals to kill rapidly dividing cells. Examples of FDA approved antineoplastic drugs include cisplatin, doxorubicin, and paclitaxel. Since most of these drugs are nonspecific, they also damage normal tissues as well as the aberrant tumors. As a result, non-specific therapies have multiple side effects, which include myelosuppression, mucositis, alopecia, nephrotoxicity, and genotoxcity. In order to minimize these issues, researchers have begun to conjugate antineoplastic chemicals with targeting moieties or encapsulate drugs into nanoparticles decorated with compounds, peptides, or proteins that recognize specific cellular receptors, which are upregulated by the neoplastic cells. The targeting moieties aid in the accumulation of these drugs within the blood vessels of carcinomas, while keeping concentrations low in the systemic circulation. Thus, targeted delivery systems are able to minimize the unwanted side effects and increase the efficacy of chemotherapies.
    ASME 2011 Summer Bioengineering Conference; 06/2011
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    ABSTRACT: Bis(1,3-dimethylimidazol-2-ylidene)silver(I) nitrate and bis(4,5-dichloro-1,3-dimethylimidazol-2-ylidene)silver(I) nitrate were prepared by reacting the corresponding imidazolium nitrate salts with silver oxide. Bis(1,3-dimethylimidazol-2-ylidene)gold(I) nitrate and bis(4,5-dichloro-1,3-dimethylimidazol-2-ylidene)gold(I) nitrate salts were prepared via transmetallation of their silver precursors with chloro dimethylsulfide gold. The anticancer properties were determined using NCI-H460 lung cancer cells. Efficacy was established by comparison of the gold and silver compounds with cisplatin.Graphical abstractTwo silver(I)-N-heterocyclic carbene (NHC) complexes were prepared by reacting corresponding imidazolium nitrate salts with silver oxide. Two gold(I)-NHC compounds were prepared via transmetallation of their silver precursors with chloro dimethylsulfide gold. Anticancer properties were determined using NCI-H460 lung cancer cells. Efficacy was established by comparison of the compounds with cisplatin.Research highlights► Synthesis of two silver(I) N-heterocyclic carbene complexes. ► Synthesis of two gold(I) N-heterocyclic carbene complexes. ► Anticancer activity of test compounds against H460 lung cancer cells. ► Efficacy not superior to cisplatin.
    Journal of Organometallic Chemistry 01/2011; 696(5):1066-1071. · 2.00 Impact Factor
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    ABSTRACT: Due to the properties of silver as an antimicrobial, our research group has synthesized many different silver carbene complexes. Two new silver N-heterocyclic carbene complexes derived from 4,5-dichloroimidazole and theobromine bearing methyl benzoate substituents were synthesized by in situ carbene formation using silver acetate as the base in the reaction. The new compounds were fully characterized by several methods including NMR spectroscopy and X-ray crystallography. Preliminary antimicrobial efficacy studies against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli were conducted. The results of this study demonstrated antimicrobial efficacy of the two complexes comparable to silver nitrate, showing their potential for use in the treatment of bacterial infections.
    Inorganica Chimica Acta 12/2010; 364(1):125-131. · 1.69 Impact Factor
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    ABSTRACT: The reactions of HCl, PCl(5), and a crown ether (12-crown-4 or 18-crown-6) in CHCl(3) under anaerobic conditions give complexes of the superacid HPCl(6): [H(12-crown-4)][PCl(6) ] and [H(18-crown-6)(2)][PCl(6)]. The crystal structures indicate that the proton lies roughly in the center of the 12-crown-4 molecule in [H(12-crown-4)][PCl(6) ] whereas it lies between two oxygen atoms of two different 18-crown-6 molecules in [H(18-crown-6)(2)][PCl(6)].
    Journal of the American Chemical Society 11/2010; · 10.68 Impact Factor
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    ABSTRACT: The binding interactions between SQ2 squaraine dye and cucurbit[8]uril (CB8) effectively removes the aggregation of SQ2 in aqueous solution by forming a 1 : 1 inclusion complex. The resulting SQ2.CB8 complex exhibits highly selective fluorescence quenching by Hg(2+) ions, as a result of the synergetic binding between CB8, SQ2 and metal cation.
    Chemical Communications 06/2010; 46(23):4073-5. · 6.38 Impact Factor

Publication Stats

370 Citations
205.03 Total Impact Points

Institutions

  • 2003–2014
    • University of Akron
      • Department of Chemistry
      Akron, Ohio, United States
  • 2012
    • University of California, Berkeley
      • College of Chemistry
      Berkeley, CA, United States
  • 2006
    • Middle East Technical University
      • Department of Chemistry
      Ankara, Ankara, Turkey
    • Case Western Reserve University
      • Department of Chemistry
      Cleveland, OH, United States
  • 2004
    • Bharathidasan University
      Tiruchchināppalli, Tamil Nādu, India