Methane diffusion mechanism in catenated metal–organic frameworks

In this work, molecular dynamics simulations were performed to investigate the gas diffusion mechanism in catenated metal–organic frameworks (MOFs), for which methane was adopted as a probe and two catenated IRMOFs with interwoven structure, IRMOF-11 and IRMOF-13, were considered. This work reveals that the diffusion pathways of methane molecules in catenated MOFs are mainly governed by the strong confinement in catenation regions, leading to a 3D diffusion along the sheets formed by the A-regions (xy-direction) as well as from one A-region to another by crossing a B-region (z-direction). In addition, the present work shows that the effect of catenation on methane diffusivity is very large, much larger than that on hydrogen diffusivity at room temperature, and that both adsorption selectivity and dynamic selectivity of gas mixtures may be enhanced largely in catenated MOFs, indicating that catenation is a good strategy to improve the overall performance of a material as a membrane in separation applications.     

Molecular simulations of adsorption and separation of acetylene and methane and their binary mixture on MOF-5, HKUST-1 and MOF-505 metal–organic frameworks

In this work, the adsorption of acetylene and its binary mixture with methane on MOF-5, HKUST-1 and MOF-505 was studied using Grand Canonical Monte Carlo molecular simulations. The preferred adsorption sites of acetylene and methane molecules into metal–organic frameworks (MOFs) were investigated. The simulated adsorption isotherms of acetylene on MOF-5 and MOF-505 agreed well with the experimental ones without any reparameterisation of the potential parameters but for HKUST-1 the interaction parameters of the acetylene and copper ion were reparameterised. Comparisons of the calculated adsorption isotherms of acetylene in the studied MOFs showed that the MOF-5 had the lowest adsorption capacity. Our results revealed that guest molecules were most adsorbed on the entrance windows of the octagon pore of HKUST-1, while the preferred adsorption sites were large pores and on the metal ion cluster of MOF-505 and MOF-5, respectively. Adsorption of binary mixtures of methane and acetylene on MOF-5, HKUST-1 and MOF-505 revealed that acetylene adsorption is higher than that of methane. Finally, the results showed that C₂H₂/CH₄ selectivity values on HKUST-1 are significantly higher than on MOF-505 and MOF-5. The preferred adsorption sites of acetylene and methane in an equimolar binary mixture were calculated and discussed.     

Molecular simulations in metal–organic frameworks for diverse potential applications

As a new class of intriguing nanoporous materials, metal–organic frameworks (MOFs) have been considered for diverse potential applications. The number of MOFs synthesised to date is extremely large; thus, experimental testing alone is economically expensive and practically formidable. With rapidly growing computational resources, molecular simulation has become an indispensable tool to characterise, screen and design MOFs. Our research group has conducted comprehensive simulation studies in MOFs for carbon capture, hydrocarbon separation, alcohol adsorption and biofuel purification, water treatment, bio- and chiral separation and drug loading; furthermore, mechanical moduli, structural transition and thermal conductivity have also been examined. These systematic simulation studies are summarised in this review to demonstrate that simulation at a molecular level can secure the quantitative interpretation of experimental observation, provide the microscopic insight from bottom-up and facilitate the development of new MOFs.     

Semi-analytical mean-field model for predicting breathing in metal–organic frameworks

A new semi-analytical mean-field model is proposed to rationalise breathing of MIL-53 type materials. The model is applied on two case studies, the guest-induced breathing of MIL-53(Cr) with CO₂ and CH₄, and the phase transformations for MIL-53(Al) upon xenon adsorption. Experimentally, MIL-53(Cr) breathes upon CO₂ adsorption, which was not observed for CH₄. This result could be ascribed to the stronger interaction of carbon dioxide with the host matrix. For MIL-53(Al) a phase transition from the large pore phase could be enforced to an intermediate phase with volumes of about 1160–1300 Å³, which corresponds well to the phase observed experimentally upon xenon adsorption. Our thermodynamic model correlates nicely with the adsorption pressure model proposed by Coudert et al. Furthermore the model can predict breathing behaviour of other flexible materials, if the user can determine the free energy of the empty host, the interaction energy between a guest molecule and the host matrix and the pore volume accessible to the guest molecules. This will allow to generate the osmotic potential from which the equilibria can be deduced and the anticipated experimentally observed phase may be predicted.     

Continuous fractional component Monte Carlo simulations of high-density adsorption in metal–organic frameworks

The continuous fractional component Monte Carlo method, which was designed to overcome difficulties with insertions and deletions of molecules, is modified to include configurational bias Monte Carlo methods and is further extended to binary systems. The modified method is shown to correctly predict adsorption of Ar in silicalite, Xe and Kr in HKUST-1, and enantiomers in a homochiral metal–organic framework. The modified method is also found to be approximately an order of magnitude more efficient in inserting and deleting molecules than traditional configurational bias grand canonical Monte Carlo simulations in dense systems.     

Computational exploration of metal–organic frameworks: examples of advances in crystal structure predictions and electronic structure tuning

The purpose of this article is to consider some recent developments in the area of the computational chemistry of metal–organic frameworks (MOFs), and more specifically on their crystal structure prediction and electronic structures. We intend here to illustrate how computational approaches might be powerful tool for the discovery of new families of hybrid frameworks, helping to understand their often complex energy landscapes. Also, MOFs have attracted a lot of attention due to their potential use for photocatalysis and optoelectronic, making it necessary to develop strategies to control their electronic structures. We will show how recent computational studies in this area have allowed a better understanding of their electronic properties and their potential tunability, highlighting when they have given successful guidelines for the discovery of novel MOFs with targeted properties.     

Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage,metastatic tumor burden,and doxorubicin–cyclophosphamide chemotherapy

Abnormal accumulation of myeloid-derived suppressor cells (MDSC) is an important mechanism of tumor immune evasion. Cyclophosphamide (CTX) has also been shown in non-tumor bearing animals to cause transient surges in MDSC. Knowledge of MDSC is primarily based on preclinical work, and to date only few published studies have involved cancer patients. The goal of this study was to test the hypothesis that circulating MDSC levels correlate with clinical cancer stage, CTX-based chemotherapy, and metastatic tumor burden. Whole blood was collected from 106 newly diagnosed solid tumor patients (stages I–IV). Percentages of circulating MDSC (Lin^−/Lo, HLA DR−, CD33⁺CD11b⁺) were determined prior to initiation of systemic therapy. In 17 early stage breast cancer patients receiving doxorubicin–cyclophosphamide chemotherapy every 14 days (ddAC) blood was collected on day 1 of each cycle. Circulating MDSC were significantly increased in cancer patients of all stages relative to healthy volunteers. A significant correlation between circulating MDSC and clinical cancer stage was also observed. Moreover, among stage IV patients, those with extensive metastatic tumor burden had the highest percent and absolute number of MDSC. Significant increases in circulating MDSC were observed with ddAC when compared with pretreatment levels. Circulating MDSC levels correlate with clinical cancer stage, ddAC, and metastatic tumor burden. This information must be incorporated into the design of future trials exploring immune-based therapeutic strategies. Pharmacologic modulation of MDSC should also be tested in future clinical trials.     

Fabrication of an organic–inorganic nanocomposite carrier for enzyme immobilization based on metal–organic coordination

An organic–inorganic nanocomposite which combined mesoporous silica SBA-15 and chitosan using a carboxyl functionalized ionic liquid as the bridging agent (SBA@CS) was successfully fabricated, and was used to immobilize porcine pancreas lipase (PPL) by physical adsorption, cross-linking and metal–organic coordination, respectively. The as-prepared carriers were characterized by scanning electron microscopy, Fourier transform infrared and energy-dispersive X-ray spectroscopy. Compared with immobilization onto the pure mesoporous silicon material SBA-15, all the batches of PPL immobilized onto organic–inorganic nanocomposites showed higher activity, improved stability and reusability as well as better resistance to pH and temperature changes. Among the immobilized PPLs, immobilization based on Co²⁺ coordination (SBA@CS-Co-PPL) produced the best enzymatic properties. The maximum immobilization efficiency and specific activity of 79.6% and 1975.8 U g⁻¹ were obtained with SBA@CS-Co, separately. More importantly, the activity of immobilized enzyme can still maintain 84.0% after 10 times of reuse. These results demonstrated that thus prepared organic–inorganic nanocomposite could be an ideal carrier for enzyme immobilization by metal–organic coordination.     

The synthesis and anticancer effects of a range of natural and unnatural hop β-acids on breast cancer cells

The β-acids derived from hops (Humulus lupulus L.) are polyphenols classified as lupulones. As part of our on-going interest in the pharmacognosy of these natural products we were keen to investigate the anticancer activity of lupulone 1 as well as individual lupulone congeners. To achieve this we undertook the synthesis of natural as well as unnatural lupulone derivatives and evaluated them for their anticancer activity against the breast cancer cell lines MCF-7 and MDA-MB-231.The results of our investigations revealed that all of the novel unnatural lupulone derivatives that were synthesised were found to be more toxic to MDA-MB-231 cell lines at 72 h than the parent lupulone 1 itself (except for the α-substituent R¹ was CH₃). Further investigations confirmed that the novel lupulone derivatives were very efficient at killing cancer cells by apoptosis but appear to do so in a time-dependant process. This outcome may be of great significance as MDA-MB-231 cell lines are characterised by an aggressive phenotype with a propensity to invade other tissue, to form metastases as well as an ability to become insensitive to chemotherapeutic agents.     

Analysis of the cytotoxic effects of ruthenium–ketoconazole and ruthenium–clotrimazole complexes on cancer cells

Ruthenium-based compounds have intriguing anti-cancer properties, and some of these novel compounds are currently in clinical trials. To continue the development of new metal-based drug combinations, we coupled ruthenium (Ru) with the azole compounds ketoconazole (KTZ) and clotrimazole (CTZ), which are well-known antifungal agents that also display anticancer properties. We report the activity of a series of 12 Ru–KTZ and Ru–CTZ compounds against three prostate tumor cell lines with different androgen sensitivity, as well as cervical cancer and lymphoblastic lymphoma cell lines. In addition, human cell lines were used to evaluate the toxicity against non-transformed cells and to establish selectivity indexes. Our results indicate that the combination of ruthenium and KTZ/CTZ in a single molecule results in complexes that are more cytotoxic than the individual components alone, displaying in some cases low micromolar CC₅₀ values and high selectivity indexes. Additionally, all compounds are more cytotoxic against prostate cell lines with lower cytotoxicity against non-transformed epidermal cell lines. Some of the compounds were found to primarily induce cell death via apoptosis yet weakly interact with DNA. Our studies also demonstrate that the cytotoxicity induced by our Ru-based compounds is not directly related to their ability to interact with DNA.     

DHEAS prevents pro-metastatic and proliferative effects of 17ß-estradiol on MCF-7 breast cancer cells

It is generally assumed that circulating dehydroepiandrosterone sulfate (DHEAS) can be desulfated and further metabolized to estrogen, which is of concern for all patients with estrogen-responsive breast cancer. We addressed this issue by comparing the effects of DHEAS, its desulfated form DHEA, and 17ß-estradiol on human metastatic, estrogen-responsive MCF-7 breast cancer cells.Physiological concentrations of DHEAS promoted phosphorylation of Erk1/2, whereas DHEA and 17ß-estradiol failed to stimulate Erk1/2 phosphorylation, indicating that the sulfated steroid acts as an autonomous hormone. Exposure of MCF-7 cells to 17ß-estradiol stimulated cell proliferation and the expression of pro-metastatic and pro-invasive elements such as claudin-1, matrix metalloproteinase 9 (MMP9), and the CC chemokine ligand 2 (CCL2). In contrast, treatment with DHEAS did not stimulate these responses but prevented all of the actions of 17ß-estradiol, and as a consequence cell migration and invasion were completely inhibited.The results of this study not only challenge the assumption that DHEAS poses a danger as an endogenous source of estrogen, they rather favor the idea that keeping DHEAS levels within a physiological range might be supportive in treating estrogen-responsive breast cancer.     

Combined chemotherapy of platinum and fluorouracil promotes T cell–mediated antitumor immunity

The two-drug combined chemotherapy of platinum and fluorouracil has been reported to efficiently kill tumor cells as the first-line treatment for advanced gastric cancer.However,the effect of these drugs on T cells remains unclear.Here,we showed that T cells including CD4+T cells and CD8+T cells of the patients with advanced gastric cancer after platinum and fluorouracil chemotherapy exhibited enhanced ex vivo proliferation ability as compared to that before chemotherapy.In addition,platinum and fluorouracil also promoted the differentiation of human T cells into Th1 and Th9 subtypes and cytotoxic T lymphocytes(CTLs)in vitro and in vivo.Accordingly,the combination therapy greatly suppressed tumor growth with increased tumor infiltration of Th1,Th9,and CTL cells in a mouse tumor model.Moreover,in activated T cells,long-term treatment with these two drugs further facilitates T cell activation along with promoted nuclear factor-κB(NF-κB)activation.Our findings demonstrate a previously unidentified function of platinum and fluorouracil combination chemotherapy in promoting T cell–mediated antitumor immunity.     

New perspectives in triple-negative breast cancer therapy based on treatments with TGFβ1 siRNA and doxorubicin

Molecular and Cellular Biochemistry - Alzheimer’s disease (AD) is a public health issue worldwide. Berberine (Ber) acts as the neuroprotective role in an animal experiment of AD. MicroRNA-188...     

Estrogen-independent effects of ER-α36 in ER-negative breast cancer

Estrogen receptor-alpha 36 (ER-α36) is a variant of ER-α that has been found to be expressed in conventional ER (ER-α66)-negative breast cancer cell lines and human breast cancer samples. In this study, we found that, using immunohistochemical study, ER-α36 expression was significantly higher in ER-negative tumors than in ER-positive tumors although the expression was not associated with other clinicopathological characteristics. We then constructed an ER-α36-specific microRNA hairpin vector and established stable ER-α36 knockdown cells, and found that the knockdown cells were more sensitive to paclitaxel; the c-Jun N-terminal kinase pathway appeared to be involved in the mechanism. Downregulation of ER-α36 also resulted in decreased migration and invasion. These changes were estrogen independent. Our findings indicated that target ER-α36 may be a strategy for treating ER-negative breast cancers.