Theoretical investigation on the fluorescent sensing mechanism for recognizing formaldehyde: TDDFT calculation and excited-state nonadiabatic dynamics

Inspired by the activity-based sensing method, the hydrazine-modified naphthalene derivative(Naph1) was synthesized and used as a fluorescent probe to detect formaldehyde(FA) in living cells. Through the condensation reaction between the probe Naph1 and analyte FA, researchers observed a ~14 folds enhancement of fluorescent signal around 510 nm in an experiment, realizing the high selectivity and sensitivity detection of FA. However, a theoretical understanding of the sensing mechanism was not provided in the experimental work. Given this, the light-up fluorescent detecting mechanism was in-depth unveiled by performing the time-dependent density functional theory(TDDFT) and the complete active space self-consistent field(CASSCF) theoretical calculations on excited-state intramolecular proton transfer(ESIPT)and non-adiabatic excited-state dynamics simulation. The deactivation channel of S_1/T_2 intersystem crossing(ISC) was turned off to successfully recognize FA. Insight into the ESIPT-based fluorescent detecting mechanism indicated that ESIPT was essential to light-up fluorescent probes. This work would provide a new viewpoint to develop ESIPT-based fluorescent probes for detecting reactive carbon species in vivo or vitio.

Identification of marine natural product Pretrichodermamide B as a STAT3 inhibitor for efficient anticancer therapy

The Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)regulates the expression of various critical mediators of cancer and is considered as one of the central communication nodes in cell growth and survival.Marine natural products(MNP)represent great resources for discovery of bioactive lead compounds,especially anti-cancer agents.Through the medium-throughput screening of our in-house MNP library,Pretrichodermamide B,an epidithiodiketopiperazine,was identified as a JAK/STAT3 signaling inhibitor.Further studies identified that Pretrichodermamide B directly binds to STAT3,preventing phosphorylation and thus inhibiting JAK/STAT3 signaling.Moreover,it suppressed cancer cell growth,in vitro,at low micromolar concentrations and demonstrated efficacy in vivo by decreasing tumor growth in a xenograft mouse model.In addition,it was shown that Pretrichodermamide B was able to induce cell cycle arrest and promote cell apoptosis.This study demonstrated that Pretrichodermamide B is a novel STAT3 inhibitor,which should be considered for further exploration as a promising anti-cancer therapy.