10 research outputs found
Disclosing gate-opening/closing events inside a flexible metal-organic framework loaded with CO2 by reactive and essential dynamics
We have combined reactive molecular dynamics simulations with principal component analysis to provide a clearer view of the interactions and motion of the CO2 molecules inside a metal-organic framework and the movements of the MOF components that regulate storage, adsorption, and diffusion of the guest species. The tens-of-nanometer size of the simulated model, the capability of the reactive force field tuned to reproduce the inorganic-organic material confidently, and the unconventional use of essential dynamics have effectively disclosed the gate-opening/closing phenomenon, possible coordinations of CO2 at the metal centers, all the diffusion steps inside the MOF channels, the primary motions of the linkers, and the effects of their concerted rearrangements on local CO2 relocations
Stability and potential degradation of the α′,β′-epoxyketone pharmacophore on ZnO nanocarriers: insights from reactive molecular dynamics and density functional theory calculations
We investigate the structure and dynamics of a zinc oxide nanocarrier loaded with Carfilzomib, an epoxyketone proteasome inhibitor developed for treating multiple myeloma. We demonstrate that, even though both bare and functionalized zinc oxide supports have been used for drug delivery, their interactions with the reactive functional groups of the ligands could be detrimental. This is because pharmacophores like α′,β′-epoxyketones should preserve the groups required for the drug activity and be capable of leaving the vehicle at the target site. Earlier studies showed that even when ZnO is functionalized with oleic acid surfactants, the drug could reach parts of the surface and remain stably adsorbed. Herein, we have used reactive molecular dynamics simulations and quantum chemistry calculations to explore the potential interactions of the Carfilzomib functional groups with the typical surfaces of ZnO supports. We have found that Carfilzomib can adsorb on the (0001)Zn-terminated polar surface through the carbonyl oxygens and the epoxyketone moiety. These strong connections could prevent the drug release and induce the epoxy ring opening with its consequential inactivation. Therefore, regulating the dosage to maintain the desired level of drug bioavailability is paramount. These findings emphasize the need for appropriate carrier functionalizations to efficiently entrap, transport, and release the cargo at the target sites and the crucial role played by predictive/descriptive computational techniques to complement and drive experiments to the most appropriate selections of the materials to optimize drug delivery
FT-IR Spectroscopic Analysis in tandem with chemometric tools for the characterization of Cecal Content of Mice: Effects of High Fat Diet and Beer
Metabolite profiles associated with the gut microbiota offer valuable insights into the influence of
lifestyle and dietary factors on both health and diseases in animal models and in humans. In recent
years, infrared spectroscopy has been demonstrated to be a valuable tool to investigate fecal and
cecal content [1-5]. This study focuses on investigating the metabolite composition of mice cecal
content using a fast and novel Fourier-transform infrared spectroscopy (FT-IR) method that involves
the deposition of samples onto polypropylene sheets, enabling efficient analysis and characterization
of metabolites and offering advantages such as requiring small sample quantities and minimal
preparation steps [6]. Experimental procedures included extracting the cecal content, preparing the
sample, and depositing it onto polypropylene sheets before and after filtration in 3 kDa microfiltration
units. The FT-IR spectra were acquired using a high-resolution FT-IR spectrometer equipped with
an attenuated total reflection (ATR) accessory. Preliminary results of principal component analysis
(PCA) of the FT-IR spectra demonstrate the feasibility and efficiency of the method to characterize
low molecular weight (LMW) metabolites and biomolecules in mice cecal content. Distinctive spectral
features corresponding to various metabolites were observed in four groups of mice reared for 10
weeks in the following conditions: they were fed with standard diet (19% proteins, 6% fibers, 7%
minerals and vitamins moisture, 64% carbohydrates and 4% fats), high-fat diet (26% proteins, 6 %
fibers, 7% minerals and vitamins moisture, 26% carbohydrates and 35% fats); standard diet + 0.23%
beer; high-fat diet + 0.23% beer. Our findings suggest diet-induced variations in the high and low
molecular weight metabolite profiles and showcase the potential of the developed method for
studying the impact of diet on gut metabolism. Further analysis and the interpretation of FT-IR
spectra will be conducted using also other complementary techniques to identify specific metabolites
and elucidate their variations among the different diet groups. FT-IR method with the deposition on
polypropylene sheets provides a valuable tool for the efficient, low-cost, and reliable characterization
of cecal content metabolites, eventually contributing to the understanding of the effects of healthy
lifestyles on gut composition and metabolism
Exploring the Interaction of Water with Open Metal Sites in MIL-101(Cr) by 1H NMR Relaxometry and ReaxFF Molecular Dynamics Simulations
In this work, we investigated the state of water in the metal-organic framework MIL-101(Cr) by combining 1H magic angle spinning (MAS) NMR, NMR relaxometry, and molecular dynamics (MD) simulations based on a reactive force field. The MD simulations indicated that water molecules are coordinated to the open metal sites and are organized in shells. Through 1H T2 and T1 relaxation measurements at the fixed Larmor frequency of 21 MHz, water in the intergrain spaces was distinguished from that in the intragrain mesopores of MIL-101(Cr). 1H MAS NMR measurements showed that water in the mesopores is structurally ordered, as revealed by the presence of 1H-1H residual dipolar interaction. The 1H NMR relaxometric behavior of water located in the intergrain spaces of MIL-101(Cr) as a function of the magnetic field strength, determined by fast field cycling NMR relaxometry, was interpreted extending an existing model, generally applied to paramagnetic aqua ions in solution, to the case of Cr3+ ions fixed on the surface of the metal-organic framework. The model predicts the exchange of water between the first and second shell of a Cr3+ ion, giving access to the water residence time in the first shell that would be difficult to determine using other techniques. In the temperature interval of 25-70 °C, water residence times in the range of tens of nanoseconds were found and a limited accessibility of water to the open metal sites located on the external grain surface was observed