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Eric E Simanek

Publications and source records attributed to Eric E Simanek.

13 recordsLinked to original sources
PubMed2006

A divergent route to diversity in macromolecules.

[reaction: see text] A synthetic route for obtaining functional group diversity in macromolecules is described. The route relies on the differential reactivity of substituted dichlorotriazines. Treatment of a triamine core with substituted dichlorotriazines cleanly yields tris(monochlorotriazines). Subsequent S(N)Ar reactions with amine nucleophiles bearing the functional group of interest yield diversity. If the substituent on the dichlorotriazine is a protected nucleophile, deprotection of the functionalized core allows for iterative reactions and the synthesis of star, dendritic, and hybrid macromolecules.

Catalysis↗
PubMed2006

Melamine-based organoclay to sequester atrazine.

Sequestration of aqueous atrazine by organoclays prepared from the surfactant 6-piperazin-1-yl-N,N'-bis-(1,1,3,3-tetramethyl-butyl)-(1,3,5)triazine-2,4-diamine and Gonzales bentonite was assessed using 14C-labeled atrazine. Organoclays with varying ratios of surfactant to clay were evaluated with respect to their ability to sequester atrazine from an aqueous solution. Organoclays containing 100-200 g kg-1 surfactant on a total weight basis provided the most efficient adsorption of atrazine, with apparent KOC values exceeding 5000 l kg-1 at these loading fractions. Less than 12% of sequestered atrazine was released during four sequential day long washings, supporting our expectation that the majority of the reaction of atrazine with the surfactant lead to irreversible chemical bond formation through nucleophilic aromatic substitution.

Adsorption↗
PubMed2004

In vitro and in vivo evaluation of a melamine dendrimer as a vehicle for drug delivery.

Cell-based and acute and subchronic in vivo toxicity profiles of a dendrimer based on melamine reveal that this class of molecules warrants additional study as vehicles for drug delivery. In cell culture, a substantial decrease in viability was observed at 0.1 mg/mL. For the acute studies, mice were administered 2.5, 10, 40 and 160 mg/kg of dendrimer via i.p. injection. At 160 mg/kg, 100% mortality was seen 6-12 h after injection. For the other cohorts, blood chemistry work revealed no renal damage was taking place at 48 h. Liver enzyme activity nearly doubled for the mice treated at 40 mg/kg suggesting hepatotoxicity. For the subchronic studies, three i.p. injections of 2.5-40 mg/kg of dendrimers were administered at 3-week intervals. No mortality was observed. Forty-eight hours following the last administration, blood chemistry revealed no renal damage, but liver damage was indicated by elevated serum enzyme activity at the highest dose. Histopathological data further confirms that doses up to 10 mg/kg show no hepatic damage at subchronic doses. However, subchronic doses at 40 mg/kg lead to extensive liver necrosis.

Animals↗
PubMed2004

Cytotoxicity, hemolysis, and acute in vivo toxicity of dendrimers based on melamine, candidate vehicles for drug delivery.

A small library of dendrimers was prepared from a common precursor that is available in 5 g scale in five linear steps at 56% overall yield. The precursor is a generation three dendrimer that displays 48 peripheral sites by incorporating AB4 surface groups. Manipulation of these sites provided six dendrimers that vary in the chemistry of the surface group (amine, guanidine, carboxylate, sulfonate, phosphonate, and PEGylated) that were evaluated for hemolytic potential and cytotoxicity. Cationic dendrimers were found to be more cytotoxic and hemolytic than anionic or PEGylated dendrimers. The PEGylated dendrimer was evaluated for acute toxicity in vivo. No toxicity--neither mortality nor abnormal blood chemistry based on blood urea nitrogen levels or alanine transaminase activity--was observed in doses up to 2.56 g/kg i.p. and 1.28 g/kg i.v.

Animals↗
PubMed2004

Removal of atrazine from water using covalent sequestration.

Monochlorotriazines including atrazine and its major metabolites, deethylatrazine and deisopropylatrazine, are susceptible to nucleophilic aromatic substitution. Competitive reactions to rank the relative reactivity of nucleophiles with atrazine reveal that constrained secondary amines are the most reactive. When the nucleophile is attached to a solid support, atrazine can be sequestered from solution. As proof of concept, polystyrene resins displaying constrained secondary amines are shown to sequester atrazine, deethylatrazine, and deisopropylatrazine from water. Sequestration can be followed spectrophotometrically or using a liquid chromatography mass spectrometry protocol. The kinetics of sequestration are similar to that of granulated charcoal. Evidence for covalent bond formation comes from control experiments with unreactive herbicides and degradation analysis of the solid support. Using both (1)H NMR spectroscopy and mass spectrometry, covalent adducts are identified in ratios close to what is calculated theoretically. This method for sequestration is effective at removing atrazine from pond water.

Atrazine↗
PubMed2003

Chemoselective building blocks for dendrimers from relative reactivity data.

Competition reactions for the substitution of monochlorotriazines with different amines provide relative reactivity data that can be used to identify new groups for the chemoselective syntheses of dendrimers based on melamine. Target 1 is prepared using a one-pot per generation strategy without protecting group manipulations or functional group interconversions.

Amines↗
PubMed2003

Evaluation of multivalent dendrimers based on melamine: kinetics of thiol-disulfide exchange depends on the structure of the dendrimer.

The rate of thiol-disulfide exchange of dansyl groups mediated by dithiothreitol depends on the structure of the dendrimer. In general, the rate of exchange decreases as the size of the dendrimer increases. Dendrimers with disulfides attached near the core undergo exchange more slowly than dendrimers with disulfides near the periphery. Exchange is a bimolecular (noncooperative) process between dansyl-linked disulfides and dithiothreitol. No evidence for intramolecular macrocylization (cooperative) exchange is observed. Mass spectrometry is used to follow exchange in two dendrimers, providing qualitative and quantitative information about this process. Mathematical models suggest that the rates for exchange for all disulfides of a dendrimer are similar, but increase as the exchange reaction progresses.

Computer Simulation↗
PubMed2003

Thiol-disulfide exchange yields multivalent dendrimers of melamine.

[reaction: see text] Thiol-disulfide exchange can be used to prepare multivalent conjugates of a small molecule or octapeptide displayed on dendrimers based on melamine. Exchange of four or eight thiopyridyl groups by captopril occurs at room temperature in methanol almost quantitatively. Exchange using the peptide requires higher temperatures and guanidinium chloride in DMF. While exchange on the tetravalent scaffold with four peptides is almost quantitative, sterics retard formation of the octavalent conjugate: the hexavalent conjugate forms readily.

Biomimetic Materials↗
PubMedDate not supplied

Synthesis and characterization of covalently linked single-stranded DNA oligonucleotide-dendron conjugates.

A solution-phase synthesis and characterization of covalent DNA-dendron conjugates is presented. Thiol-terminated 12-base oligonucleotides were added to second- and third-generation triazine-based dendrons via thiol/disulfide exchange chemistry. Single-stranded DNA oligonucleotides were successfully attached to dendrons at the core, the periphery, and both. Proof of structure for these architectures is derived primarily from mass spectrometry and polyacrylamide gel electrophoresis and complemented by labeling analysis using Ellman's reagent and degradation analysis using a reducing agent.

Coloring Agents↗
PubMedDate not supplied

Reduction of drug toxicity using dendrimers based on melamine.

Dendrimers based on melamine can reduce the organ toxicity of solubilized cancer drugs administered by intraperitoneal injection. Methotrexate and 6-mercaptopurine, both FDA approved anticancer drugs, are known hepatotoxins. The solubility of these molecules can be increased by mixing them with a dendrimer based on melamine. C3H mice were administered subchronic doses of methotrexate or 6-mercaptopurine with and without a solubilizing dendrimer. Forty-eight hours after dosing, the mice were sacrificed and serum was collected for biochemical analyses. The levels of alanine transaminase, ALT, were used to probe liver damage. When the drugs are encapsulated by the dendrimer, a significant reduction in hepatotoxicity is observed: ALT levels from the rescued groups (drug + dendrimer) were 27% (methotrexate) and 36% (6-mercaptopurine) lower than those of animals treated with the drug alone.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Toward the next-generation drug delivery vehicle: synthesis of a dendrimer with four orthogonally reactive groups.

The synthesis of a dendrimer based on melamine that displays multiple copies of four orthogonally reactive groups, three on the surface and one on the interior, is described. The three groups on the surface are nucleophilic and include four free hydroxyl groups, four hydroxyl groups masked as tert-butyldiphenylsilyl (TBDPS) ethers, and 16 amines masked as tert-butoxycarbonyl (BOC) groups. The core of the dendrimer displays two electrophilic monochlorotriazines. The dendrimer is available in seven linear steps (eight total steps) at 55% overall yield for the longest linear sequence.

Amines↗