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

The Nontradable Share Reform in the Chinese Stock Market

Nontradable shares (NTS) are an unparalleled feature of the ownership structure of Chinese listed companies and represented a major hurdle to domestic financial market development. After some failed attempts, in 2005 the Chinese authorities have launched a structural reform program aiming at eliminating NTS. In this paper, we evaluate the stock price effects of the actual implementation of this reform in 368 firms. The NTS reform generated a statistically significant 8 percent positive abnormal return over the event window, adjusting prices for the compensation requested by tradable shareholders. Results are consistent with the expectation of improved economic fundamentals such as better corporate governance and enhanced liquidity

Technology Transfers and the Clean Development Mechanism in a North-South General Equilibrium Model

This paper analyzes the potential welfare gains of introducing a technology transfer from Annex I to non-Annex I in order to mitigate greenhouse gas emissions. Our analysis is based on a numerical general equilibrium model for a world economy comprising two regions, North (Annex I) and South (non-Annex I). As our model allows for labor mobility between the formal and informal sectors in the South, we are also able to capture additional aspects of how the transfer influences the Southern economy. In a cooperative equilibrium, a technology transfer from the North to the South is clearly desirable from the perspective of a global social planner, since the welfare gain for the South outweighs the welfare loss for the North. However, if the regions do not cooperate, then the incentives to introduce the technology transfer appear to be relatively weak from the perspective of the North; at least if we allow for Southern abatement in the pre-transfer Nash equilibrium. Finally, by adding the emission reductions associated with the Kyoto agreement to an otherwise uncontrolled market economy, the technology transfer leads to higher welfare in both regions

Marginal Cost versus Average Cost Pricing with Climatic Shocks in Senegal: A Dynamic Computable General Equilibrium Model Applied to Water

The model simulates on a 20-year horizon, a first phase of increase in the water resource availability taking into account the supply policies by the Senegalese government and a second phase with hydrologic deficits due to demand evolution (demographic growth). The results show that marginal cost water pricing (with a subsidy ensuring the survival of the water production sector) makes it possible in the long term to absorb the shock of the resource shortage, GDP, investment and welfare increase. Unemployment drops and the sectors of rain rice, market gardening and drinking water distribution grow. In contrast, the current policy of average cost pricing of water leads the long-term economy in a recession with an agricultural production decrease, a strong degradation of welfare and a rise of unemployment. This result questions the basic tariff (average cost) on which block water pricing is based in Senegal

Cost Effectiveness in River Management: Evaluation of Integrated River Policy System in Tidal Ouse

The River Ouse forms a significant part of Humber river system, which drains about one fifth the land area of England and provides the largest fresh water source to the North Sea from UK. The river quality in the tidal river suffered from sag of dissolved oxygen (DO) during last few decades, deteriorated by the effluent discharges. The Environment Agency (EA) proposed to increase the water quality of Ouse by implementing more potent environmental policies. This paper explores the cost effectiveness of water management in the Tidal Ouse through various options by taking into account the variation of assimilative capacity of river water, both in static and dynamic scope of time. Reduction in both effluent discharges and water abstraction were considered along side with choice of effluent discharge location. Different instruments of environmental policy, the emission tax-subsidy (ETS) scheme and tradable pollution permits (TPP) systems were compared with the direct quantitative control approach. This paper at the last illustrated an empirical example to reach a particular water quality target in the tidal Ouse at the least cost, through a solution of constrained optimisation problem. The results suggested significant improvement in the water quality with less cost than current that will fail the target in low flow year

The Role of Risk Aversion and Lay Risk in the Probabilistic Externality Assessment for Oil Tanker Routes to Europe

Oil spills are a major cause of environmental concern, in particular for Europe. However, the traditional approach to the evaluation of the expected external costs of these accidents fails to take into full account the implications of their probabilistic nature. By adapting a methodology originally developed for nuclear accidents to the case of oil spills, we extend the traditional approach to the assessment of the welfare losses borne by potentially affected individuals for being exposed to the risk of an oil spill. The proposed methodology differs from the traditional approach in three respects: it allows for risk aversion; it adopts an ex-ante rather than an ex-post perspective; it allows for subjective oil spill probabilities (held by the lay public) higher than those assessed by the experts in the field. In order to illustrate quantitatively this methodology, we apply it to the hypothetical (yet realistic) case of an oil spill in the Aegean Sea. We assess the risk premiums that potentially affected individuals would be willing to pay in order to avoid losses to economic activities such as tourism and fisheries, and non-use damages resulting from environmental impacts on the Aegean coasts. In the scenarios analysed, the risk premiums on expected losses for tourism and fisheries turn out to be substantial when measured as a percentage of expected losses; by contrast, they are quite small for the case of damages to the natural environment