Imprinted Polymers for Selective Adsorption of Cholesterol from Gastrointestinal Fluids

Abstract

A series of highly cross-linked terpolymers of methacryloylated cholesterol or bile acid methyl esters, methacrylic acid, and ethyleneglycol dimethacrylate were prepared in the presence or absence of cholesterol acting as a template molecule. The polymers were freed from cholesterol by washing and the resulting adsorbents tested for cholesterol rebinding in the chromatographic mode using methanol−water as mobile phase or in the batch mode using an intestinal mimicking fluid of concentrated bile acids in water. The polymers prepared in polar solvents, favoring the apolar association of the template and the apolar face of the amphiphilic monomers, exhibited selective rebinding of cholesterol as compared to a nonimprinted blank polymer prepared identically but without cholesterol. The strongest rebinding was seen for the polymer prepared using 3β-methacryloyl-cholesterol as the functional monomer. Using a physiologically relevant intestinal-mimicking solution of cholesterol (1 mM), these polymers adsorbed ca. 17 mg cholesterol per gram dry adsorbent, whereas a nonimprinted blank polymer adsorbed ca. 13 mg. The imprinted polymers showed the highest uptake of cholesterol as compared to other adsorbents (<13 mg/g) that were expected to show high affinity for cholesterol.

Imidazolium-based functional monomers for the imprinting of the anti-inflammatory drug naproxen: Comparison of acrylic and sol–gel approaches

“…The preparation of molecularly imprinted polymers (MIP) typically involves three steps: first, a monomer-template [M-T] complex is formed via self-assembly; next, the M-T complex is polymerized with an excess of cross-linker to form a rigid polymer; finally, the template is removed, leaving behind binding cavities which are complementary in shape and functional group to the template [2]. The vast majority of MIP is based on the use of organic acrylate-type polymers: a standard procedure using a methacrylate monomer, with a nearly optimal ratio to the template molecule and crosslinker, is described in numerous works [2][3][4][5][6][7][8]. The broad applicability of methacrylic acid (MAA) as a functional monomer in MIP production is related to the fact that the carboxylic acid group serves well as a hydrogen bond and proton donor as well as a hydrogen bond acceptor [9].…”

Addictive evaluation of cholic acid-verticinone ester, a potential cough therapeutic agent with agonist action of opioid receptor

“…Then treatment of 3 with verticinone in CH 2 Cl 2 , followed by esterification, gave the compound 5α,14α-cevanin-6-O-20β-hydroxy-3β-yl-3α-tertbutyldimethylsilyloxy-7α,12α-dihydroxy-5β-cholan-24-oate, 4. In this reaction, 4-dimethylaminopyridine (DMAP) was used as a catalyst and N,N′-dicyclohexylcarbodiimide (DCC) as a dehydration agent [13] . Finally, the deprotection reaction of 4 in 5% HF [14] aqueous solution gave the desired 5α,14α-cevanin-6-O-20β-hydroxy-3β-yl-3α,7α,12α-trihydroxy-5β-cholan-24-oate, 5.…”

Phytosterol Recognition via Rationally Designed Molecularly Imprinted Polymers

“…Reagents, conditions, and yield: (i) n-propynylmagnesium bromide, THF, 0 °C, 1 h, 13%; (ii) Pd/CaCO3, Pb, quinoline, H2, EtOAc, 3 h, 99%; (iii) triethylorthopropionate, propionic acid, xylene, reflux, 1 h, 100% crude; (iv) LiAlH4, THF, 22 °C, 2 h, 98%; (v) (a) MsCl, pyridine, 22 °C, 2 h, 100% crude, (b) LiAlH4, THF, 22 °C, 21 h, 100% crude; (vi) p-TsOH, dioxane/H2O, reflux, 1 h, 73%. Nomenclature: (22S)-6β-methoxy-3α,5-cyclo-26,27-dinor-5α-cholest-23-yn-22-ol (6), (22R,23Z)-6β-methoxy-3α,5-cyclo-26,27-dinor-5α-cholest-23-en-22-ol (13), (22E,24S)-ethyl-6β-methoxy-24-methyl-3α,5-cyclo-5α-cholest-22-en-26-oate (14), (22E,24S)-6β-methoxy-24-methyl-3α,5-cyclo-5α-cholest-22-en-26-ol (15), and (22E,24R)-6β-methoxy-24-methyl-3α,5-cyclo-5α-cholest-22-ene (brassicasterol imethyl ether) (16). (12) (14), (22E,24S)-6β-methoxy-24-methyl-3α,5-cyclo-5α-cholest -22-en-26-ol (15), and (22E,24R)-6β-methoxy-24-methyl-3α,5-cyclo-5α-cholest-22-ene (brassicasterol i-methyl ether) (16).…”

“…Nomenclature: (22S)-6β-methoxy-3α,5-cyclo-26,27-dinor-5α-cholest-23-yn-22-ol (6), (22R,23Z)-6β-methoxy-3α,5-cyclo-26,27-dinor-5α-cholest-23-en-22-ol (13), (22E,24S)-ethyl-6β-methoxy-24-methyl-3α,5-cyclo-5α-cholest-22-en-26-oate (14), (22E,24S)-6β-methoxy-24-methyl-3α,5-cyclo-5α-cholest-22-en-26-ol (15), and (22E,24R)-6β-methoxy-24-methyl-3α,5-cyclo-5α-cholest-22-ene (brassicasterol imethyl ether) (16). (12) (14), (22E,24S)-6β-methoxy-24-methyl-3α,5-cyclo-5α-cholest -22-en-26-ol (15), and (22E,24R)-6β-methoxy-24-methyl-3α,5-cyclo-5α-cholest-22-ene (brassicasterol i-methyl ether) (16).…”

“…Such MIPs can exhibit a 'molecular memory' for the template or structurally related molecular analogues [11][12][13]. To date, most studies involving sterol-related molecularly imprinted polymers, usually involving non-covalent self-assembly approaches, have focused on cholesterol [14][15][16][17][18][19][20][21][22][23] or estradiol [24][25][26][27]. The focus of this investigation was to explore an alternative method for the generation of a covalently imprinted MIP based on the use of the cleavable stigmasterol methacrylate as template, in silico determination of optimal co-monomer-template ratios, batch binding studies with several sterol analogues, and molecular modeling of the binding interactions.…”