Uncovering the Pathway of Serine Octamer Magic Number Cluster Formation during Electrospray Ionization: Experiments and Simulations.

Electrospray ionization (ESI) of serine (Ser) solution generates Ser8H+ as an abundant magic number cluster. ESI clustering of most other solutes yields nonspecific stoichiometries. It is unclear why Ser8H+ dominates in the case of Ser, and how Ser8H+ forms during ESI. Even the location of Ser8H+ formation is contentious (in solution, in ESI droplets, or elsewhere). Here we unravel key aspects of the l-Ser8H+ formation pathway. Harsh ion sampling conditions promote the collision-induced dissociation (CID) of regular ESI analytes. Unexpectedly, Ser8H+ was seemingly resistant against CID during ion sampling, despite its extremely low tandem mass spectrometry (MS/MS) stability. This unusual behavior reveals that Ser8H+ forms during ion sampling. We propose the following pathway: (1) Nonspecific Ser clusters are released when ESI droplets evaporate to dryness. These initial clusters cover a wide size range, from a few Ser to hundreds or thousands of monomers. (2) The clusters undergo dissociation during ion sampling, mostly via successive loss of neutral monomers. For any source activation voltage, there is a subpopulation of clusters for which this CID cascade tends to terminate at the octamer level, culminating in Ser8H+-dominated product distributions. Mobile proton molecular dynamics simulations were used to model the entire pathway. Ser8H+ structures formed in these simulations were consistent with ion mobility experiments. The most compact structures resembled the model of [Scutelnic, V. J. Am. Chem. Soc. 2018, 140, 7554-7560], with numerous intermolecular salt bridges and H-bonds. Our findings illustrate how the interplay of association and dissociation reactions across phase boundaries can culminate in magic number clusters.

Synthesis of green benzamide-decorated UiO-66-NH2 for biomedical applications.

Metal-organic frameworks (MOFs) biocompatible systems can host enzymes/bacteria/viruses. Herein we synthesized a series of fatty acid amide hydrolase (FAAH)-decorated UiO-66-NH2 based on Citrus tangerine leaf extract for drug delivery and biosensor applications. Five chemically manipulated FAAH-like benzamides were localized on the UiO-66-NH2 surface with physical interactions. Comprehensive cellular and molecular analyses were conducted on HEK-293, HeLa, HepG2, PC12, MCF-7, and HT-29 cell lines (cytotoxicity assessment after 24 and 48 h). MTT results proved above 95 and 50% relative cell viability in the absence and presence of the drug, respectively. A complete targeted drug-releasing capability of nanocarriers was demonstrated after capping with leaf extract from Citrus tangerine, with a stimuli-responsive effect in acidic media. Targeted delivery was complete to the nucleus and cytoplasm of HT-29 cell, but merely to the cytoplasm of HeLa cell lines. Nanocarrier could be targeted for drug delivery to the cytoplasm of the HeLa cell line and to both the nucleus and cytoplasm of HT-29 cell lines. MOF-based nanocarriers proved authentic in vivo towards kidney and liver tissues with targeted cancerous cells efficiently. Besides, FAAH-like molecules revealed optical biosensor potential with high selectivity (even ˂5 nM LOD) towards ssDNA, sgRNA, and Anti-cas9 proteins.