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Chemical Structure| 1137725-46-2 Chemical Structure| 1137725-46-2

Structure of 1137725-46-2

Chemical Structure| 1137725-46-2

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Green, Kevin A ; Kulkarni, Anuja S ; Jankoski, Penelope E ; Newton, Thomas B ; Derbigny, Blaine ; Clemons, Tristan D , et al.

Abstract: The self-assembly of Janus-type amphiphilic hybrid block copolymers composed of hydrophilic/hydrophobic layers has shown promise for drug encapsulation and delivery. Saccharides have previously been incorporated to improve the biocompatibility of self-assembled structures; however, glycopolymer block copolymers have been less explored, and their structure−property relationships are not well understood. In this study, novel glycopolymer-branched poly(lactic acid) (PLA) block copolymers were synthesized via thiol−ene coupling and their composition-dependent morphologies were elucidated. Stability as a function of pH, dye uptake capabilities, and cytotoxicity were evaluated. Systems with a hydrophilic weight ratio of 30% were found to produce bilayer nanoparticles, while systems with a hydrophilic weight ratio of 60% form micelles upon self-assembly in aqueous media. Regardless of composition and morphology, all systems exhibited uptake of both hydrophobic (curcumin, DL % from 4.25 to 11.55) and hydrophilic (methyl orange, DL % from 4.08 to 5.88) dye molecules with release profiles dependent on composition. Furthermore, all of the nanoparticles exhibited low cytotoxicity, confirming their potential for biomedical applications.

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Jessica L. Lawson ; Ram Prasad Sekar ; ryelle R. E Wright ; Grant Wheeler ; Jillian Yanes ; Jordan Estridge , et al.

Abstract: Synthetic polymers—chemically versatile and affordable materials—are promising nanocarriers for the intracellular delivery of nucleic acids. Lipophilic polycations with incorporated hydrophilic co-monomers effectively complex and deliver bulky nu- cleic acid payloads such as plasmids (pDNA). The spatial distribution of lipophilic cations and neutral, hydrophilic repeat units governs the pDNA binding, serum stability, pDNA delivery efficiency, and cytocompatibility of polymer–pDNA complexes, 1 or polyplexes. Yet, investigators have focused predominantly on block and statistical copolymers while largely ignoring gradient copolymers, where the density of lipophilic cations diminishes gradually along polymer backbones. Seeking to obtain gradient copolymers that combine the colloidal stability of block copolymers with the high trans-fection efficacy of statistical copolymers, we synthesized length- and compositionally- equivalent gradient copolymers (G1–G3) via reversible addition fragmentation chain transfer polymerization (in addition to equivalent statistical (S) and block (B) copolymer references). We mapped microstructure-dependent differences in polymer–pDNA, pDNA loading per polyplex, pDNA conformational changes, and binding thermodynamics via static light scattering, circular dichroism spectroscopy, and isothermal titration calorime- try, respectively. B exhibited vastly different binding profiles compared to the other four copolymers while having the highest pDNA loading capacity. Further, we discovered that subtle modulation of gradient steepness is an effective strategy to negotiate trade- offs among pDNA delivery efficiency, cytotoxicity, and colloidal stability in serum. For instance, G1 overcame the colloidal instability of S polyplexes in serum, while maintaining comparable transfection efficiency. Similarly, G1 showed the highest TxV value (from Pareto front analysis), indicating that lipophilic cation distribution in copolymer microstructure promotes cell viability along with high transfection. Microstructural con- trasts did not elicit differences in complement activation, while S triggered the highest hemolysis. Our work demonstrates that the spatial distribution of lipophilic cations is an effective, albeit underutilized, design handle to improve the physical properties and biological performance of polymeric gene carriers.

Keywords: gene therapy ; gradient copolymers ; block copolymers ; statistical copolymers ; microstructure ; pDNA delivery

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Product Details of [ 1137725-46-2 ]

CAS No. :1137725-46-2
Formula : C9H13NO2S3
M.W : 263.40
SMILES Code : CC(SC(SCC)=S)(C#N)CCC(O)=O
MDL No. :MFCD27978407
InChI Key :KEWSCDNULKOKTG-UHFFFAOYSA-N
Pubchem ID :58283676

Safety of [ 1137725-46-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Application In Synthesis of [ 1137725-46-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1137725-46-2 ]

[ 1137725-46-2 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 6066-82-6 ]
  • [ 1137725-46-2 ]
  • [ 1195771-65-3 ]
YieldReaction ConditionsOperation in experiment
79% With dicyclohexyl-carbodiimide; In chloroform; at 0 - 20℃; for 23h; To a solution of CEPA (1.00 g, 3.79 mmol) in CHCl3 (20 mL) at 0 C were added NHS (524 mg, 4.55 mmol) and DCC (940 mg, 4.55 mmol). The reaction mixture was stirred at 0 C for 1 h and then at room temperature for 22 hrs. The by-product, dicyclohexylurea (DCU) was filtered off and the filtrate was concentrated in vacuo. The crude product was purified by flash column chromatography using ethyl acetate and hexane (3: 1 to 1: 1) as the eluents, and the resulting product NHS-CEPA was obtained (1.08 g, 79.0%) as a yellow powder. 1H-NMR (400 MHz, CDCl3, ppm):delta= 3.36 (2H, q, J= 8.0 Hz, -CH2-S), 2.97-2.90 (2H, m, -CH2-), 2.85 (4H, s, -CH2-CH2-), 2.71-2.48 (2H, m, -CH2-), 1.89 (3H, s, -CH3), 1.38 (3H, t, J= 8.0 Hz, -CH3).
 

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