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Metal-organic frameworks (MOFs) are known to facilitate energy-efficient separations of important industrial chemical feedstocks. Here, we report how a class of green MOFs-namely CD-MOFs-exhibits high shape selectivity toward aromatic hydrocarbons. CD-MOFs, which consist of an extended porous network of γ-cyclodextrins (γ-CDs) and alkali metal cations, can separate a wide range of benzenoid compounds as a result of their relative orientation and packing within the transverse channels formed from linking (γ-CD)6 body-centered cuboids in three dimensions. Adsorption isotherms and liquid-phase chromatographic measurements indicate a retention order of ortho- > meta- > para-xylene. The persistence of this regioselectivity is also observed during the liquid-phase chromatography of the ethyltoluene and cymene regioisomers. In addition, molecular shape-sorting within CD-MOFs facilitates the separation of the industrially relevant BTEX (benzene, toluene, ethylbenzene, and xylene isomers) mixture. The high resolution and large separation factors exhibited by CD-MOFs for benzene and these alkylaromatics provide an efficient, reliable, and green alternative to current isolation protocols. Furthermore, the isolation of the regioisomers of (i) ethyltoluene and (ii) cymene, together with the purification of (iii) cumene from its major impurities (benzene, n-propylbenzene, and diisopropylbenzene) highlight the specificity of the shape selectivity exhibited by CD-MOFs. Grand canonical Monte Carlo simulations and single component static vapor adsorption isotherms and kinetics reveal the origin of the shape selectivity and provide insight into the capability of CD-MOFs to serve as versatile separation platforms derived from renewable sources.

Messenger RNA (mRNA) vaccine development for preventive and therapeutic applications has evolved rapidly over the last decade. The mRVNA vaccine has proven therapeutic efficacy in various applications, including infectious disease, immunotherapy, genetic disorders, regenerative medicine, and cancer. Many mRNA vaccines have made it to clinical trials, and a couple have obtained FDA approval. This emerging therapeutic approach has several advantages over conventional methods: safety; efficacy; adaptability; bulk production; and cost-effectiveness. However, it is worth mentioning that the delivery to the target site and in vivo degradation and thermal stability are boundaries that can alter their efficacy and outcomes. In this review, we shed light on different types of mRNA vaccines, their mode of action, and the process to optimize their development and overcome their limitations. We also have explored various delivery systems focusing on the nanoparticle-mediated delivery of the mRNA vaccine. Generally, the delivery system plays a vital role in enhancing mRNA vaccine stability, biocompatibility, and homing to the desired cells and tissues. In addition to their function as a delivery vehicle, they serve as a compartment that shields and protects the mRNA molecules against physical, chemical, and biological activities that can alter their efficiency. Finally, we focused on the future considerations that should be attained for safer and more efficient mRNA application underlining the advantages and disadvantages of the current mRNA vaccines. [ABSTRACT FROM AUTHOR]

Gene editing, especially with clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9), has advanced gene function science. Gene editing's rapid advancement has increased its medical/clinical value. Due to its great specificity and efficiency, CRISPR/Cas9 can accurately and swiftly screen the whole genome. This simplifies disease-specific gene therapy. To study tumor origins, development, and metastasis, CRISPR/Cas9 can change genomes. In recent years, tumor treatment research has increasingly employed this method. CRISPR/Cas9 can treat cancer by removing genes or correcting mutations. Numerous preliminary tumor treatment studies have been conducted in relevant fields. CRISPR/Cas9 may treat gene-level tumors. CRISPR/Cas9-based personalized and targeted medicines may shape tumor treatment. This review examines CRISPR/Cas9 for tumor therapy research, which will be helpful in providing references for future studies on the pathogenesis of malignancy and its treatment. [ABSTRACT FROM AUTHOR]

Aedes aegypti mosquitoes carrying self-spreading, virus-blocking Wolbachia bacteria are being deployed to suppress dengue transmission. However, there are challenges in applying this technology in extreme environments. We introduced two Wolbachia strains into Ae. aegypti from Saudi Arabia for a release program in the hot coastal city of Jeddah. Wolbachia reduced infection and dissemination of dengue virus (DENV2) in Saudi Arabian mosquitoes and showed complete maternal transmission and cytoplasmic incompatibility. Wolbachia reduced egg hatch under a range of environmental conditions, with the Wolbachia strains showing differential thermal stability. Wolbachia effects were similar across mosquito genetic backgrounds but we found evidence of local adaptation, with Saudi Arabian mosquitoes having lower egg viability but higher adult desiccation tolerance than Australian mosquitoes. Genetic background effects will influence Wolbachia invasion dynamics, reinforcing the need to use local genotypes for mosquito release programs, particularly in extreme environments like Jeddah. Our comprehensive characterization of Wolbachia strains provides a foundation for Wolbachia-based disease interventions in harsh climates. Author summary: Wolbachia bacteria live inside the cells of many insects including mosquitoes. Wolbachia strains can block the transmission of dengue and other arboviruses transmitted by Aedes mosquitoes and are being introduced around the world for disease control. The success of this strategy relies on the ability of Wolbachia to spread locally by causing cytoplasmic incompatibility (embryo death when infected males mate with uninfected females), on Wolbachia having limited fitness costs in local mosquito hosts, and on Wolbachia persisting in the local mosquito background in the environmental conditions that mosquitoes encounter. Here we comprehensively assess the feasibility of using two Wolbachia strains in releases with Aedes aegypti mosquitoes in the challenging environment of Jeddah, Saudi Arabia. We show effective dengue virus blocking and incompatibility in both strains in the local mosquito genetic background but higher fitness costs for one strain which may offset its ability to maintain higher infection levels under the fluctuating temperatures expected in Jeddah. We find that the Jeddah Ae. aegypti are more resistant to desiccation, highlighting the importance of establishing infections in the local genetic background. These findings directly inform the employment of Wolbachia strategies in Jeddah and emphasize the value of testing the local context. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a zoonotic disease transmitted in humans by the bite of Leishmania-infected phlebotomine sandflies. Each year approximately 58,500 cases of leishmaniasis are diagnosed across the globe, with a mortality rate of nearly seven percent. There are over 20 parasitic strains of Leishmania which are known to cause distinct types of leishmaniasis and pose an endemic threat to humans worldwide. Therefore, it is crucial to develop potential medications and vaccines to combat leishmaniasis. However, the task of developing therapeutic solutions is challenging due to Leishmania's digenetic lifecycle. The challenge is further intensified by cases of resistance against the available drugs. Owing to these challenges, the conventional drug development regimen is further limited by target discovery and ligand suitability for the targets. On the other hand, as an added advantage, the emergence of omics-based tools, such as high-end proteomics, transcriptomics and genomics, has hastened the pace of target discovery and target-based drug development. It is now becoming apparent that multi-omics convergence and an inter-connected systems approach is less time-consuming and more cost-effective for any drug-development process. This comprehensive review is an attempt to summarize the current knowledge on the muti-omics approach in drug development against leishmaniasis. In particular, it elaborates the potential target identification from secreted proteins in various stages of Leishmania infection and also illustrates the convergence of transcriptomic and genomic data towards the collective goal of drug discovery. This review also provides an understanding of the potential parasite's drug targets and drug resistance characteristics of the parasite, which can be used in designing effective and specific therapeutics. [ABSTRACT FROM AUTHOR]

Simple Summary: Aedes aegypti is a mosquito that is responsible for spreading viral diseases including dengue fever, Zika, and chikungunya. Disease spread can be reduced by releasing mosquitoes containing bacteria known as Wolbachia, which inhibit transmission. Before such releases, it is important to collect data about where Ae. aegypti occur in urban landscapes and how populations vary over space and time. In this study, we present a pre-release analysis of mosquito populations using ovitraps (traps that provide a substrate for female mosquitoes to lay eggs), in Jeddah, Saudi Arabia. Our study contains a number of important findings. Firstly, we showed that there was no difference in the numbers of eggs laid between basement and non-basement locations. Secondly, we showed that, for some study sites, there was significant spatial structure to populations, meaning that where numbers of eggs were high (or low) they tended to remain high (or low) on average for many hundreds of meters. We also found that when mosquitoes are present in an area during the dry season, they tend to remain into the wet season; however, regions of high egg production could change between seasons. This suggests that in Jeddah's arid environment, the quality of breeding environments is inconsistent over time. Releases of Aedes aegypti carrying Wolbachia bacteria are known to suppress arbovirus transmission and reduce the incidence of vector-borne diseases. In planning for Wolbachia releases in the arid environment of Jeddah, Saudi Arabia, we collected entomological data with ovitraps across a 7-month period in four locations. Herein, we show that mosquito presence in basements does not differ from that of non-basement areas of buildings. In modelling mosquito presence across the study sites, we found the spatial structure to be statistically significant in one of the four sites, while a significant spatial structure was found for egg production data across three of the four sites. The length scales of the spatial covariance functions fitted to the egg production data ranged from 143 m to 574 m, indicating that high productivity regions can be extensive in size. Rank-correlation analyses indicated that mosquito presence tended to persist from the dry to wet season, but that egg production ranks at locations could reverse. The data suggest that, in Jeddah, the quality of the local environment for breeding can vary over time. The data support the feasibility of dry season releases but with release numbers needing to be flexible depending on local rates of invasion. [ABSTRACT FROM AUTHOR]

In October 2021, a case of acute hepatic failure without any known cause was identified in the United States of America. Upon further investigation, other children aged 1–6 years were reported to have the same liver failure, and some of them were positive for adenovirus 41 type F. On 21 April 2022, the Centers for Disease Control and Prevention (CDC) released an alert after 74 cases were identified in United Kingdom (UK) between 5 and 8 April in children below 10 years of age, some of whom were also found to be positive for SARS-CoV-2. All the patients showed symptoms such as vomiting, diarrhea, jaundice, and abdominal pain. The patients' liver enzymes were remarkably increased. A total of 650 cases had been reported from 33 countries as of 27 May 2022, among which 222 cases were reported in the UK alone. No connection with SARS-CoV-2 or its vaccine has been found so far. However, the suspected cause is adenovirus, including its genomic variations, because its pathogenesis and laboratory investigations have been positively linked. Until further evidence emerges, hygiene precautions could be helpful to prevent its spread. [ABSTRACT FROM AUTHOR]

Herpes labialis, caused by herpes simplex virus type 1, is usually characterized by painful skin or mucosal lesions. Penciclovir (PV) tablets are found to be effective against herpes labialis but suffer from poor oral bioavailability. This study aimed to combine the benefits of PV and lavender oil (LO), which exhibits anesthetic activity, in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for the treatment of herpes labialis. Toward this purpose, LO (oil), Labrasol:Labrafil M1944 CS in the ratio of 6:4 (surfactant mixture), and Lauroglycol-FCC (co-surfactant, selected based on the solubility of PV) were evaluated as the independent factors using a distance quadratic mixture design. The formulation was optimized for the minimum globule size and maximum stability index and was determined to contain 14% LO, 40.5% Labrasol:Labrafil 1944 (6:4), and 45.5% Lauroglycol-FCC. The optimized PV-LOSNEDDS was embedded in chitosan hydrogel and the resulting formulations coded by (O3) were prepared and evaluated. The rheological studies demonstrated a combined pseudoplastic and thixotropic behavior with the highest flux of PV permeation across sheep buccal mucosa. Compared to a marketed 1% PV cream, the O3 formulation exhibited a significantly higher and sustained PV release, nearly twice the PV permeability, and a relative bioavailability of 180%. Overall, results confirm that the O3 formulation can provide an efficient delivery system for PV to reach oral mucosa and subsequent prolonged PV release. Thus, the PV-LO-SNEDDS embedded oral gel is promising and can be further evaluated in clinical settings to establish its therapeutic use in herpes labialis. [ABSTRACT FROM AUTHOR]

The comment has corrected highly debatable information, in which we claimed that the SA binds only to the hemagglutinin proteins rather than the S protein, especially for SARS-CoV-2 and MERS-CoV. The hemagglutinin is known as the main envelop glycoprotein of influenza B virus, inducing receptor binding, while neuraminidase works as a separate glycoprotein. Sialic acid (SA) is the glycoprotein that is densely projected on the surface of different mammalian cells including lung epithelial cells. Development of a Colorimetric Tool for SARS-CoV-2 and Other Respiratory Viruses Detection Using Sialic Acid Fabricated Gold Nanoparticles. [Extracted from the article]

Since the advent of mechanically interlocked molecules (MIMs), many approaches to templating their formation using various different noncovalent bonding interactions have been introduced and explored. In particular, employing radical-pairing interactions between BIPY.+ units, the radical cationic state of 4,4′-bipyridinium (BIPY2+) units, in syntheses is not only a convenient but also an attractive source of templation because of the unique properties residing in the resulting catenanes and rotaxanes. Herein, we report a copper-mediated procedure that enables the generation, in the MIM-precursors, of BIPY.+ radical cations, while the metal itself, which is oxidized to CuI, catalyzes the azide-alkyne cycloaddition reactions that result in the efficient syntheses of two catenanes and one rotaxane, assisted by radical-pairing interactions between the BIPY.+ radical cations. This procedure not only provides a fillip for making and investigating the properties of Coulombically challenged catenanes and rotaxanes, but it also opens up the possibility of synthesizing artificial molecular machines which operate away from equilibrium. [ABSTRACT FROM AUTHOR]

Covalent and supramolecular polymerizations, both of which offer their own unique advantages, have emerged as popular strategies for making artificial materials. Herein, we describe a concurrent covalent and supramolecular polymerization strategy-namely, one which utilizes 1) a bis-azide-functionalized diazaperopyrenium dication that undergoes polymeriation covalently with a bis-alkyne-functionalized biphenyl derivative in one dimension as a result of a rapid and efficient β-cyclodextrin(CD)-accelerated, cucurbit[6]uril(CB)-templated azide-alkyne cycloaddition, while 2) the aromatic core of the dication is able to dimerize in a criss-cross fashion by dint of π-π interactions, enabling simultaneous supramolecular assembly, resulting in an extended polymer network in an orthogonal dimension. [ABSTRACT FROM AUTHOR]

Sialic acid that presents on the surface of lung epithelial cells is considered as one of the main binding targets for many respiratory viruses, including influenza and the current coronavirus (SARS-CoV-2) through the viral surface protein hemagglutinin. Gold nanoparticles (Au NPs) are extensively used in the diagnostic field owing to a phenomenon known as 'surface plasmonic resonance' in which the scattered light is absorbed by these NPs and can be detected via UV-Vis spectrophotometry. Consequently, sialic acid conjugated Au NPs (SA-Au NPs) were utilized for their plasmonic effect against SARS-CoV-2, influenza B virus, and Middle-East respiratory syndrome-related coronavirus (MERS) in patients' swab samples. The SA-Au NPs system was prepared by a one-pot synthesis method, through which the NPs solution color changed from pale yellow to dark red wine color, indicting its successful preparation. In addition, the SA-Au NPs had an average particle size of 30 ± 1 nm, negative zeta potential (−30 ± 0.3 mV), and a UV absorbance of 525 nm. These NPs have proven their ability to change the color of the NPs solutions and patients' swabs that contain SARS-CoV-2, influenza B, and MERS viruses, suggesting a rapid and straightforward detection tool that would reduce the spread of these viral infections and accelerate the therapeutic intervention. [ABSTRACT FROM AUTHOR]

Multidrug resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) is a superbug pathogen that causes serious diseases. One of the main reasons for the lack of the effectiveness of antibiotic therapy against infections caused by this resistant pathogen is the recalcitrant nature of MRSA biofilms, which results in an increasingly serious situation worldwide. Consequently, the development of innovative biofilm inhibitors is urgently needed to control the biofilm formation by this pathogen. In this work, we thus sought to evaluate the biofilm inhibiting ability of some promising antibiofilm agents such as zinc oxide nanoparticles (Zno NPs), proteinase K, and hamamelitannin (HAM) in managing the MRSA biofilms. Different phenotypic and genotypic methods were used to identify the biofilm producing MDR MRSA isolates and the antibiofilm/antimicrobial activities of the used promising agents. Our study demonstrated strong antibiofilm activities of ZnO NPs, proteinase K, and HAM against MRSA biofilms along with their transcriptional modulation of biofilm (intercellular adhesion A, icaA) and quorum sensing (QS) (agr) genes. Interestingly, only ZnO NPs showed a powerful antimicrobial activity against this pathogen. Collectively, we observed overall positive correlations between the biofilm production and the antimicrobial resistance/agr genotypes II and IV. Meanwhile, there was no significant correlation between the toxin genes and the biofilm production. The ZnO NPs were recommended to be used alone as potent antimicrobial and antibiofilm agents against MDR MRSA and their biofilm-associated diseases. On the other hand, proteinase-K and HAM can be co-administrated with other antimicrobial agents to manage such types of infections. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a significant human pathogen, it possesses almost all of the known antimicrobial resistance mechanisms. Quorum sensing (QS) is an intercellular communication system that orchestrates bacterial virulence and its targeting is an effective approach to diminish its pathogenesis. Repurposing of drugs is an advantageous strategy, in this study we aimed to repurpose the anti-diabetic drugs sitagliptin, metformin and vildagliptin as anti-QS in P. aeruginosa. The effects of sub-inhibitory concentrations of the tested drugs on the expression of QS-encoding genes and QS-regulated virulence factors were assessed. The protective activity of tested drugs on P. aeruginosa pathogenesis was evaluated in vivo on mice. In silico analysis was performed to evaluate the interference capabilities of the tested drugs on QS-receptors. Although the three drugs reduced the expression of QS-encoding genes, only sitagliptin inhibited the P. aeruginosa virulence in vitro and protected mice from it. In contrast, metformin showed significant in vitro anti-QS activities but failed to protect mice from P. aeruginosa. Vildagliptin did not show any in vitro or in vivo efficacy. Sitagliptin is a promising anti-QS agent because of its chemical nature that hindered QS-receptors. Moreover, it gives an insight to consider their similar chemical structures as anti-QS agents or even design new chemically similar anti-QS pharmacophores. [ABSTRACT FROM AUTHOR]

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans; the second-largest and most deadly outbreak to date occurred in Saudi Arabia. The dromedary camel is considered a possible host of the virus and also to act as a reservoir, transmitting the virus to humans. Here, we studied evolutionary relationships for 31 complete genomes of betacoronaviruses, including eight newly sequenced MERS-CoV genomes isolated from dromedary camels in Saudi Arabia. Through bioinformatics tools, we also used available sequences and 3D structure of MERS-CoV spike glycoprotein to predict MERS-CoV epitopes and assess antibody binding affinity. Phylogenetic analysis showed the eight new sequences have close relationships with existing strains detected in camels and humans in Arabian Gulf countries. The 2019-nCov strain appears to have higher homology to both bat coronavirus and SARS-CoV than to MERS-CoV strains. The spike protein tree exhibited clustering of MERS-CoV sequences similar to the complete genome tree, except for one sequence from Qatar (KF961222). B cell epitope analysis determined that the MERS-CoV spike protein has 24 total discontinuous regions from which just six epitopes were selected with score values of >80%. Our results suggest that the virus circulates by way of camels crossing the borders of Arabian Gulf countries. This study contributes to finding more effective vaccines in order to provide long-term protection against MERS-CoV and identifying neutralizing antibodies. [ABSTRACT FROM AUTHOR]

Wolbachia (Hertig 1936) (Rickettsiales: Ehrlichiaceae) has emerged as a valuable biocontrol tool in the fight against dengue by suppressing the transmission of the virus through mosquitoes. Monitoring the dynamics of Wolbachia is crucial for evaluating the effectiveness of release programs. Mitochondrial (mtDNA) markers serve as important tools for molecular tracking of infected mitochondrial backgrounds over time but require an understanding of the variation in release sites. In this study, we investigated the mitochondrial lineages of Aedes aegypti (Linnaeus 1762) in Jeddah, Saudi Arabia, which is a prospective release site for the "wAlbBQ" Wolbachia-infected strain of this mosquito species. We employed a combination of comprehensive mitogenomic analysis (including all protein-coding genes) and mtDNA marker analysis (cox1 and nad5) using data collected from Jeddah. We combined our mitogenome and mtDNA marker data with those from previous studies to place mitochondrial variation in Saudi Arabia into a broader global context. Our findings revealed the presence of 4 subclades that can be broadly categorized into 2 major mitochondrial lineages. Ae. aegypti mosquitoes from Jeddah belonged to both major lineages. Whilst mitogenomic data offered a higher resolution for distinguishing Jeddah mosquitoes from the wAlbBQ strain, the combination of cox1 and nad5 mtDNA markers alone proved to be sufficient. This study provides the first important characterization of Ae. aegypti mitochondrial lineages in Saudi Arabia and offers essential baseline information for planning future molecular monitoring efforts during the release of Wolbachia-infected mosquitoes., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America.)

Leishmaniasis is a zoonotic disease transmitted in humans by the bite of Leishmania -infected phlebotomine sandflies. Each year approximately 58,500 cases of leishmaniasis are diagnosed across the globe, with a mortality rate of nearly seven percent. There are over 20 parasitic strains of Leishmania which are known to cause distinct types of leishmaniasis and pose an endemic threat to humans worldwide. Therefore, it is crucial to develop potential medications and vaccines to combat leishmaniasis. However, the task of developing therapeutic solutions is challenging due to Leishmania 's digenetic lifecycle. The challenge is further intensified by cases of resistance against the available drugs. Owing to these challenges, the conventional drug development regimen is further limited by target discovery and ligand suitability for the targets. On the other hand, as an added advantage, the emergence of omics-based tools, such as high-end proteomics, transcriptomics and genomics, has hastened the pace of target discovery and target-based drug development. It is now becoming apparent that multi-omics convergence and an inter-connected systems approach is less time-consuming and more cost-effective for any drug-development process. This comprehensive review is an attempt to summarize the current knowledge on the muti-omics approach in drug development against leishmaniasis. In particular, it elaborates the potential target identification from secreted proteins in various stages of Leishmania infection and also illustrates the convergence of transcriptomic and genomic data towards the collective goal of drug discovery. This review also provides an understanding of the potential parasite's drug targets and drug resistance characteristics of the parasite, which can be used in designing effective and specific therapeutics.

SGLT2 inhibitors are a novel class of FDA approved anti-diabetes drugs. They act by blocking the SGLT2 protein, which prevents glucose reabsorption, leading in enhance glucose excretion and lower blood glucose levels. In diabetic patients, SGLT2 inhibitors have been linked to urinary tract infections (UTIs). Therefore, the development of novel SGLT2 inhibitors with no adverse effects is a need of time. With this purpose, in this study, 48164natural compounds from ZINC database were screened targeting both the SGLT2 and FimH protein using insilico approaches. FimH has been discovered as a promising target for preventing and treating UTIs. The hit compounds ZINC69481892, ZINC1612996, and ZINC4039265 exhibited strong binding with both SGLT2 and FimH with binding energies values of -9.88, -8.96, and -10.57 kcal/mol for SGLT2, and -7.86, -7.01, and -8.92 kcal/mol for FimH, which is higher than that of controls (-6.78 kcal/mol (Empaglifozolin for SGLT2) and -5.14 kcal/mol (Heptyl α-d-mannopyranoside for FimH)). Hits were found to bind with key residues of both SGLT2 and FimH protein. In addition, physiochemical properties showed that these compounds have good drug-likeness properties. Therefore, we anticipate that if these compounds are investigated further, might be potential SGLT2 inhibitors with less uropathogenic adverse effects., Competing Interests: There are no conflicts of interest., (© 2022 Biomedical Informatics.)

Although ibuprofen is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs), it exhibits poor solubility in aqueous and physiological environments as a free acid. In order to improve its oral bioavailability and rate of uptake, extensive research into the development of new formulations of ibuprofen has been undertaken, including the use of excipients as well as ibuprofen salts, such as ibuprofen lysinate and ibuprofen, sodium salt. The ultimate goals of these studies are to reduce the time required for maximum uptake of ibuprofen, as this period of time is directly proportional to the rate of onset of analgesic/anti-inflammatory effects, and to increase the half-life of the drug within the body; that is, the duration of action of the effects of the drug. Herein, we present a pharmaceutical cocrystal of ibuprofen and the biocompatible metal-organic framework called CD-MOF. This metal-organic framework (MOF) is based upon γ-cyclodextrin (γ-CD) tori that are coordinated to alkali metal cations (e.g., K + ions) on both their primary and secondary faces in an alternating manner to form a porous framework built up from (γ-CD) 6 cubes. We show that ibuprofen can be incorporated within CD-MOF-1 either by (i) a crystallization process using the potassium salt of ibuprofen as the alkali cation source for production of the MOF or by (ii) absorption and deprotonation of the free-acid, leading to an uptake of 23-26 wt % of ibuprofen within the CD-MOF. In vitro viability studies revealed that the CD-MOF is inherently not affecting the viability of the cells with no IC 50 value determined up to a concentration of 100 μM. Bioavailability investigations were conducted on mice, and the ibuprofen/CD-MOF pharmaceutical cocrystal was compared to control samples of the potassium salt of ibuprofen in the presence and absence of γ-CD. From these animal studies, we observed that the ibuprofen/CD-MOF-1 cocrystal exhibits the same rapid uptake of ibuprofen as the ibuprofen potassium salt control sample with a peak plasma concentration observed within 20 min, and the cocrystal has the added benefit of a 100% longer half-life in blood plasma samples and is intrinsically less hygroscopic than the pure salt form.

A strategy for creating foldameric oligorotaxanes composed of only positively charged components is reported. Threadlike components-namely oligoviologens-in which different numbers of 4,4'-bipyridinium (BIPY(2+)) subunits are linked by p-xylylene bridges, are shown to be capable of being threaded by cyclobis(paraquat-p-phenylene) (CBPQT(4+)) rings following the introduction of radical-pairing interactions under reducing conditions. UV/vis/NIR spectroscopic and electrochemical investigations suggest that the reduced oligopseudorotaxanes fold into highly ordered secondary structures as a result of the formation of BIPY(•+) radical cation pairs. Furthermore, by installing bulky stoppers at each end of the oligopseudorotaxanes by means of Cu-free alkyne-azide cycloadditions, their analogous oligorotaxanes, which retain the same stoichiometries as their progenitors, can be prepared. Solution-state studies of the oligorotaxanes indicate that their mechanically interlocked structures lead to the enforced interactions between the dumbbell and ring components, allowing them to fold (contract) in their reduced states and unfold (expand) in their fully oxidized states as a result of Coulombic repulsions. This electrochemically controlled reversible folding and unfolding process, during which the oligorotaxanes experience length contractions and expansions, is reminiscent of the mechanisms of actuation associated with muscle fibers.

Polyaromatic compounds are well-known to intercalate DNA. Numerous anticancer chemotherapeutics have been developed upon the basis of this recognition motif. The compounds have been designed such that they interfere with the role of the topoisomerases, which control the topology of DNA during the cell-division cycle. Although many promising chemotherapeutics have been developed upon the basis of polyaromatic DNA intercalating systems, these candidates did not proceed past clinical trials on account of their dose-limiting toxicity. Herein, we discuss an alternative, water-soluble class of polyaromatic compounds, the 2,9-diazaperopyrenium dications, and report in vitro cell studies for a library of these dications. These investigations reveal that a number of 2,9-diazaperopyrenium dications show similar activities as doxorubicin toward a variety of cancer cell lines. Additionally, we report the solid-state structures of these dications, and we relate their tendency to aggregate in solution to their toxicity profiles. The addition of bulky substituents to these polyaromatic dications decreases their tendency to aggregate in solution. The derivative substituted with 2,6-diisopropylphenyl groups proved to be the most cytotoxic against the majority of the cell lines tested. In the solid state, the 2,6-diisopropylphenyl-functionalized derivative does not undergo π···π stacking, while in aqueous solution, dynamic light scattering reveals that this derivative forms very small (50-100 nm) aggregates, in contrast with the larger ones formed by dications with less bulky substituents. Alteration of the aromaticitiy in the terminal heterocycles of selected dications reveals a drastic change in the toxicity of these polyaromatic species toward specific cell lines.