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Uncaging carbon disulfide. Delivery platforms for potential pharmacological applications: a mechanistic approach.

ABSTRACT: We describe the kinetics of the formation and decay of a series of dithiocarbamates under physiological conditions. The goal is to provide a toolbox of compounds that release CS2 by well-defined kinetics in such media. Carbon disulfide is a known environmental toxin, but there is fragmentary evidence suggesting that CS2 may have bioregulatory and/or therapeutic roles in mammalian biology. Further investigation of such roles will require methodologies for controlled delivery of this bioactive small molecule to specific targets. Reported here are mechanistic and computational studies of CS2 release from a series of dithiocarbamate anions (DTCs), where R2N represents several different secondary amido groups. The various DTCs under physiologically relevant conditions show a tremendous range of reactivities toward CS2 dissociation with decay lifetimes ranging from ?2 s for imidazolidyldithiocarbamate (ImDTC-) to ?300 s for diisopropyldithiocarbamate (DIDTC-) to >24 h for pyrrolidinyldithiocarbamate (PDTC-) in pH 7.4 phosphate buffer solution at 37 °C. Thus, by making the correct choice of these tools, one can adjust the flux of CS2 in a biological experiment, while the least reactive DTCs could serve as controls for evaluating the potential effects of the dithiocarbamate functionality itself. Kinetics studies and density functional calculations are used to probe the mechanism of DTC- decay. In each case, the rate of CS2 dissociation is acid dependent; however, the DFT studies point to a mechanistic pathway for ImDTC- that is different than those for DIDTC-. The role of general acid catalysis is also briefly probed.

SUBMITTER: DeMartino AW

PROVIDER: S-EPMC5633850 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

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Uncaging carbon disulfide. Delivery platforms for potential pharmacological applications: a mechanistic approach.

DeMartino Anthony W AW Souza Maykon Lima ML Ford Peter C PC

Chemical science 20170904 10

We describe the kinetics of the formation and decay of a series of dithiocarbamates under physiological conditions. The goal is to provide a toolbox of compounds that release CS<sub>2</sub> by well-defined kinetics in such media. Carbon disulfide is a known environmental toxin, but there is fragmentary evidence suggesting that CS<sub>2</sub> may have bioregulatory and/or therapeutic roles in mammalian biology. Further investigation of such roles will require methodologies for controlled delivery ...[more]

PMID: 29081951

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Project description:In recent years, researchers focused their attention on mesoporous silica nanoparticles (MSNs) owing to the considerable advancements of the characterization methods, especially electron microscopy methods, which allowed for a clear visualization of the pore structure and the materials encapsulated within the pores, along with the X-ray diffraction (small angles) methods and specific surface area determination by Brunauer-Emmett-Teller (BET) technique. Mesoporous silica gained important consideration in biomedical applications thanks to its tunable pore size, high surface area, surface functionalization possibility, chemical stability, and pore nature. Specifically, the nature of the pores allows for the encapsulation and release of anti-cancer drugs into tumor tissues, which makes MSN ideal candidates as drug delivery carriers in cancer treatment. Moreover, the inner and outer surfaces of the MSN provide a platform for further functionalization approaches that could enhance the adsorption of the drug within the silica network and the selective targeting and controlled release to the desired site. Additionally, stimuli-responsive mesoporous silica systems are being used as mediators in cancer therapy, and through the release of the therapeutic agents hosted inside the pores under the action of specific triggering factors, it can selectively deliver them into tumor tissues. Another important application of the mesoporous silica nanomaterials is related to its ability to extract different hazardous species from aqueous media, some of these agents being antibiotics, pesticides, or anti-tumor agents. The purpose of this paper is to analyze the methods of MSN synthesis and related characteristics, the available surface functionalization strategies, and the most important applications of MSN in adsorption as well as release studies. Owing to the increasing antibiotic resistance, the need for developing materials for antibiotic removal from wastewaters is important and mesoporous materials already proved remarkable performances in environmental applications, including removal or even degradation of hazardous agents such as antibiotics and pesticides.

Dataset Information

Uncaging carbon disulfide. Delivery platforms for potential pharmacological applications: a mechanistic approach.

Publications

Uncaging carbon disulfide. Delivery platforms for potential pharmacological applications: a mechanistic approach.

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