Modeling Kinetics and Thermodynamics of Guest Encapsulation into the [ML] 12- Supramolecular Organometallic Cage

Altres ajuts: Acord transformatiu CRUE-CSICThe encapsulation of molecular guests into supramolecular hosts is a complex molecular recognition process in which the guest displaces the solvent from the host cavity, while the host deforms to let the guest in. An atomistic description of the association would provide valuable insights on the physicochemical properties that guide it. This understanding may be used to design novel host assemblies with improved properties (i.e., affinities) toward a given class of guests. Molecular simulations may be conveniently used to model the association processes. It is thus of interest to establish efficient protocols to trace the encapsulation process and to predict the associated magnitudes Δ G and Δ G ⧧. Here, we report the calculation of the Gibbs energy barrier and Gibbs binding energy by means of explicit solvent molecular simulations for the [GaL] 12- metallocage encapsulating a series of cationic molecules. The Δ G ⧧ for encapsulation was estimated by means of umbrella sampling simulations. The steps involved were identified, including ion-pair formation and naphthalene rotation (from L ligands of the metallocage) during the guest's entrance. The Δ G values were computed using the attach-pull-release method. The results reveal the sensitivity of the estimates on the force field parameters, in particular on atomic charges, showing that higher accuracy is obtained when charges are derived from implicit solvent quantum chemical calculations. Correlation analysis identified some indicators for the binding affinity trends. All computed magnitudes are in very good agreement with experimental observations. This work provides, on one side, a benchmarked way to computationally model a highly charged metallocage encapsulation process. This includes a nonstandard parameterization and charge derivation procedure. On the other hand, it gives specific mechanistic information on the binding processes of [GaL] 12- at the molecular level where key motions are depicted. Taken together, the study provides an interesting option for the future design of metal-organic cages

A Tetraferrocenyl-Resorcinarene Cavitand as a Redox-Switchable Host of Ammonium Salts

Tetraannulation of a resorcinarene-octaamino cavitand with ferrocenecarboxaldehyde allows the preparation of a tetrabenzimidazole-resorcinarene cavitand with four ferrocenyl moieties directly linked to the C2 atom of the imidazole units. Oxidation of the four ferrocenyl moieties produces important structural modifications of the molecule, as indicated by DFT calculations performed for the neutral and tetraoxidized forms of the cavitand. By means of 1H NMR spectroscopic analysis, the encapsulating properties of the new tetraferrocenyl-resorcinarene cavitand toward a series of ammonium salts were evaluated, and a clear cutoff point in binding affinity with respect to size was observed. Cyclic voltammetric studies allowed us to estimate the relative association constants for the neutral and oxidized forms of the cavitand, thus indicating that the guest was bound to the neutral (reduced) state of the cavitand and was released from the oxidized form. These redox-addressable conformational and binding properties of the resorcinarene-tetraferrocenyl cavitand constitute all the necessary features of a redox-switchable molecular gripper. By means of mass-spectrometric analysis, we could unambiguously confirm the molar stoichiometry of the host–guest complex (1:1) and assess the strong guest encapsulation, as indicated by triggering the covalent coupling between host and guest in the gas phase.MEC of Spain (CTQ2011-24055/BQU and CTQ2014-54071-P) and the Universitat Jaume I (P11B2014-02

Treatment of osteolytic solitary painful osseous metastases with radiofrequency ablation or cryoablation: a retrospective study by propensity analysis

The present study aimed to measure the improvement in pain relief and quality of life in patients with osteolytic solitary painful bone metastasis treated by cryoablation (CA) or radiofrequency ablation (RFA). Fifty patients with solitary osteolytic painful bone metastases were retrospectively studied and selected by propensity analysis. Twenty-five patients underwent CA and the remaining twenty-five underwent RFA. Pain relief, in terms of complete response (CR), the number of patients requiring analgesia and the changes in self-rated quality of life (QoL) were measured following the two treatments. Thirty-two percent of patients treated by CA experienced a CR at 12 weeks versus 20% of patients treated by RFA. The rate of CR increased significantly with respect to baseline only in the group treated by CA. In both groups there was a significant change in the partial response with respect to baseline (36% in the CA group vs. 44% in the RFA group). The recurrence rate in the CA and RFA groups was 12% and 8%, respectively. The reduction in narcotic medication requirements with respect to baseline was only significant in the group treated by CA. A significant improvement in self-rated QoL was observed in both groups. The present study seems to suggest that CA only significantly improves the rate of CR and decreases the requirement of narcotic medications. Both CA and RFA led to an improvement in the self-rated QoL of patients after the treatments. However, the results of the present study should be considered as preliminary and to serve as a framework around which future trials may be designed

Treatment of Solitary Painful Osseous Metastases with Radiotherapy, Cryoablation or Combined Therapy: Propensity Matching Analysis in 175 Patients

aim of this study was to identify outcomes in pain relief and quality of life in patients with a solitary painful osseous metastasis treated by radiotherapy, cryoablation or the combination using a propensity score matching study design

Is it really advantageous to operate proximal femoral fractures within 48 h from diagnosis? – A multicentric retrospective study exploiting COVID pandemic-related delays in time to surgery

Objectives: Hip fractures in the elderly are common injuries that need timely surgical management. Since the beginning of the pandemic, patients with a proximal femoral fracture (PFF) experienced a delay in time to surgery. The primary aim of this study was to evaluate a possible variation in mortality in patients with PFF when comparing COVID-19 negative versus positive. Methods: This is a multicentric and retrospective study including 3232 patients with PFF who underwent surgical management. The variables taken into account were age, gender, the time elapsed between arrival at the emergency room and intervention, pre-operative American Society of Anesthesiology score, pre-operative cardiovascular and respiratory disease, and 10-day/1-month/6-month mortality. For 2020, we had an additional column, “COVID-19 swab positivity.” Results: COVID-19 infection represents an independent mortality risk factor in patients with PFFs. Despite the delay in time-to-surgery occurring in 2020, no statistically significant variation in terms of mortality was detected. Within our sample, a statistically significant difference was not detected in terms of mortality at 6 months, in patients operated within and beyond 48 h, as well as no difference between those operated within or after 12/24/72 h. The mortality rate among subjects with PFF who tested positive for COVID-19 was statistically significantly higher than in patients with PFF who tested. COVID-19 positivity resulted in an independent factor for mortality after PFF. Conclusion: Despite the most recent literature recommending operating PFF patients as soon as possible, no significant difference in mortality was found among patients operated before or after 48 h from diagnosis