A general supramolecular adjuvant for pesticides based on host-guest recognition.

BACKGROUND: Pesticides are indispensable in agriculture and can effectively improve the yields and quality of crops. Due to their weak water solubility, most pesticides need to be dissolved by adding solubilizing adjuvants. In this work, based on molecular recognition of the macrocyclic host, we developed a novel supramolecular adjuvant, called sulfonated azocalix[4]arene (SAC4A), which significantly improves the water solubility of pesticides. RESULTS: SAC4A presents multiple advantages, including high water solubility, strong binding affinity, universality, and simple preparation. SAC4A showed an average binding constant value of 1.66 × 105 M-1 for 25 pesticides. Phase solubility results indicated that SAC4A increased the water solubility of pesticides by 80-1310 times. The herbicidal, fungicidal, and insecticidal activities of supramolecular formulations were found to be superior to those of technical pesticides, and the herbicidal effects were even better than those of commercial formulations. CONCLUSION: Overall results revealed the potential of SAC4A to improve the solubility and effectiveness of pesticides, providing a new development idea for the application of adjuvants in agriculture. © 2023 Society of Chemical Industry.

Synthesis, Structural Elucidation, and Anti-Inflammatory Activity of a Water-Soluble Derivative of Arctiin.

The poor oral bioavailability of arctiin caused by its low water solubility is the biggest obstacle in developing it as a drug. In this work, a new water-soluble glucuronide derivative of arctiin (arctigenin-4'-O-glucuronide) was synthesized through 2,2,6,6-tetramethylpiperidine 1-oxyl mediated oxidation reaction. Subsequently, its anti-inflammatory effect was evaluated by mice acute lung injury model in vivo. The results showed that the glucuronide derivative of arctiin not only had better water solubility but also displayed improved anti-inflammatory activity in vivo, thus serving as an innovative compound in the drug development of arctiin.

Radiotherapy-Induced Cleavage of Quaternary Ammonium Groups Activates Prodrugs in Tumors.

Cleavage chemistry offers a new chance to activate chemotherapeutic prodrugs in a tumor-selective manner, yet developing spatiotemporally controllable cleavage chemistry with deep tissue penetration is still a great challenge. Herein, we present a novel radiotherapy-triggered cleavage chemistry that enables controlled drug release in tumors. Quaternary ammonium groups are identified as masking groups that can be efficiently removed by hydrated electrons (e-aq ) from water radiolysis. The subsequently released tertiary amines can be anti-cancer toxins or readily release functional molecules via 1,6-elimination. This radiotherapy-induced cleavage works successfully in living cells and tumor-bearing mice, showing remarkable treatment efficacy when the mice are given carfilzomib prodrug and radiotherapy. This strategy provides a new perspective for combinational radiochemotherapy, which is the first-line treatment for over 50 % of cancer patients.

Radiotherapy Reduces N-Oxides for Prodrug Activation in Tumors.

Precisely activating chemotherapeutic prodrugs in a tumor-selective manner is an ideal way to cure cancers without causing systemic toxicities. Although many efforts have been made, developing spatiotemporally controllable activation methods is still an unmet challenge. Here, we report a novel prodrug activation strategy using radiotherapy (X-ray). Due to its precision and deep tissue penetration, X-ray matches the need for altering molecules in tumors through water radiolysis. We first demonstrated that N-oxides can be effectively reduced by hydrated electrons (e-aq) generated from radiation both in tubes and living cells. A screening is performed to investigate the structure-reduction relationship and mechanism of the e-aq-mediated reductions. We then apply the strategy to activate N-oxide prodrugs. The anticancer drug camptothecin (CPT)-based N-oxide prodrug shows a remarkable anticancer effect upon activation by radiotherapy. This radiation-induced in vivo chemistry may enable versatile designs of radiotherapy-activated prodrugs, which are of remarkable clinical relevance, as over 50% of cancer patients take radiotherapy.