Synthesis of Highly pH‐Responsive Glucose Poly(orthoester)

Abstract

AbstractpH‐Responsive polymers have great potential in biomedical applications, including the selective delivery of preloaded drugs to tissues with low pH values. These polymers usually contain acid‐labile linkages such as esters and acetals/ketals. However, these linkages are only mildly pH‐responsive with relatively long half‐lives (t1/2). Orthoester linkages are more acid‐labile, but current methods suffer from synthetic challenges and are limited to the availability of monomers. To address these limitations, a sugar poly(orthoester) was synthesized as a highly pH‐responsive polymer. The synthesis was achieved by using 2,3,4‐tri‐O‐acetyl‐α‐D‐glucopyranosyl bromide as a difunctional AB monomer and tetra‐n‐butylammonium iodide (TBAI) as an effective promoter. Under optimal conditions, polymers with molecular weights of 6.9 kDa were synthesized in a polycondensation manner. The synthesized glucose poly(orthoester), wherein all sugar units were connected through orthoester linkages, was highly pH‐responsive with a half‐life of 0.9, 0.6, and 0.2 hours at pH 6, 5, and 4, respectively.

Two‐Step Functionalization of Oligosaccharides Using Glycosyl Iodide and Trimethylene Oxide and Its Applications to Multivalent Glycoconjugates

“…Several groups have observed orthoester formation during glycosylation studies 15b. 19b, 20a, 25 Common methods to circumvent this side reaction include introducing a Lewis acid or applying heat to the reaction 20b. 26 Initially, we followed the method reported by Stachulsky et al.,15b utilizing NIS and triflic acid, but only 20–30 % yield of 4 was obtained.…”

“…Following the published protocol, [32,38] compounds 20 and 24 [32] were reacted with sodium ascorbate, aminoguanidine, CuSO 4 •5H 2 O, and tris(3-hydroxypropyltriazolylmethyl)amine ligand (THPTA) in PBS buffer pH 7.4 containing 5 % DMSO, under O 2 -free conditions overnight. After desalting, purification, and lyophilization procedures, the trimeric globotriaose-PADRE conjugate (25) was obtained as a fluffy white solid in 75 % yield, and was analyzed by MALDI-TOF MS and analytical HPLC (see the Supporting Information, Figure S2 and S3). The biological activity of this construct is currently under investigation.…”

“…C 18 reverse phase R f = 0. 40 H,OCH),8 H,8 H,12 124.9, 103.1, 101.9, 100.1, 78.4, 77.2, 75.3, 74.6, 74.2, 72.7, 71.9, 70.7, 70.6, 68.9, 68.7, 68.4, 67.6, 66.2, 63.2, 60.3, 60.2, 59.8, 46.9, 29.4, 23.1 Trivalent-globobotriaose/PADRE click conjugate (25) The procedure for synthesizing compound 25 was modified from previous publications. [32,38] To a 10 mL flame-dried round-bottomed flask was added 500 mL of compound 24 (1.4 mg) and 1.5 mL compound 20 (4.…”

Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment

“…In the acidic environment of tumors, the chemotherapeutic drug chlorine (triphenylphosphine) gold (I) (TPPGC) could be released due to the degradation of benzoic acid imine linker, which gave rise to the damage of mitochondria of cancer cells and their apopsis [ 34 ]. Other types of functional group include hydrazone bond [ 35 , 36 ], glycerol ester groups [ 37 ], acetal [ 38 , 39 ], cis-acotinyl [ 40 ], orthoester [ 41 , 42 ], and silyl ether [ 43 ], which are unstable under acidic conditions. These chemical bonds could be hydrolyzed rapidly under weak acidic conditions, thereby causing the changes of the chemical structures ( Table 1 ).…”

Light-Driven Polarity Switching of the Chromatographic Stationary Phase with Photoreversibility

“…Smart materials can be responsive to external stimuli, such as electric field, , light, − pH, − pressure, − and temperature, − to achieve predictable and reversible change in inherent structures and functions. Among these stimuli, light is highly advantageous to provide a superior spatial and temporal control in operation .…”