Now showing items 1-20 of 2382

    • MicroRNAs and Cancer

      Maher, S.G.; Bibby, B.A.S.; Moody, Hannah L.; Reid, G. (2015)
      MicroRNAs are a relatively new class of small, noncoding RNA species that represent a cornerstone of cell biology, with diverse roles ranging from embryonic development to aging. miRNAs function to regulate posttranscriptional gene expression, are critical to the normal function of cells, and as such are frequently dysregulated during disease processes. In this chapter, we discuss the biogenesis and mechanism of action of miRNA and their role in cancer initiation, promotion, and progression. In addition, we discuss the most recently identified dual roles of miRNA in epigenetic gene regulation; how they are both regulators and regulated. Finally, we discuss the emerging roles of miRNA as epigenetic anti-cancer therapeutics, the current research examining inhibition of oncogenic miRNAs, and studies now establishing the potential of replacing lost, tumor-suppressive miRNA.
    • MicroRNA-31 Regulates Chemosensitivity in Malignant Pleural Mesothelioma

      Moody, Hannah L.; Lind, M.; Maher, S.G. (2017-09-15)
      Malignant pleural mesothelioma (MPM) is associated with an extremely poor prognosis, and most patients initially are or rapidly become unresponsive to platinum-based chemotherapy. MicroRNA-31 (miR-31) is encoded on a genomic fragile site, 9p21.3, which is reportedly lost in many MPM tumors. Based on previous findings in a variety of other cancers, we hypothesized that miR-31 alters chemosensitivity and that miR-31 reconstitution may influence sensitivity to chemotherapeutics in MPM. Reintroduction of miR-31 into miR-31 null NCI-H2452 cells significantly enhanced clonogenic resistance to cisplatin and carboplatin. Although miR-31 re-expression increased chemoresistance, paradoxically, a higher relative intracellular accumulation of platinum was detected. This was coupled to a significantly decreased intranuclear concentration of platinum. Linked with a downregulation of OCT1, a bipotential transcriptional regulator with multiple miR-31 target binding sites, we subsequently identified an indirect miR-31-mediated upregulation of ABCB9, a transporter associated with drug accumulation in lysosomes, and increased uptake of platinum to lysosomes. However, when overexpressed directly, ABCB9 promoted cellular chemosensitivity, suggesting that miR-31 promotes chemoresistance largely via an ABCB9-independent mechanism. Overall, our data suggest that miR-31 loss from MPM tumors promotes chemosensitivity and may be prognostically beneficial in the context of therapeutic sensitivity.
    • The RAC1 target NCKAP1 plays a crucial role in progression of BRAF/PTEN -driven melanoma in mice

      Swaminathan, Karthic; Campbell, A.; Papalazarou, V.; Jaber-Hijazi, F.; Nixon, C.; McGhee, E.; Strathdee, D.; Sansom, O.J.; Machesky, L.M. (2020)
      BRAF V600E is the most common driver mutation in human cutaneous melanoma and is frequently accompanied by loss of the tumor suppressing phosphatase PTEN. Recent evidence suggests a co-operative role for RAC1 activity in BRAF V600E -driven melanoma progression and drug resistance. However, the underlying molecular mechanisms and the role of RAC1 downstream targets are not well explored. Here, we examine the role of the NCKAP1 subunit of the pentameric cytoskeletal SCAR/WAVE complex, a major downstream target of RAC1, in a mouse model of melanoma driven by BRAF V600E; PTEN loss. The SCAR/WAVE complex is the major driver of lamellipodia formation and cell migration downstream of RAC1 and depends on NCKAP1 for its integrity. Targeted deletion of Nckap1 in the melanocyte lineage delayed tumor onset and progression of a mutant Braf ; Pten loss driven melanoma mouse model. Nckap1 depleted tumors displayed fibrotic stroma with increased collagen deposition concomitant with enhanced immune infiltration. Nckap1 loss slowed proliferation and tumor growth, highlighting a role in cell cycle progression. Altogether, we propose that NCKAP1-orchestrated actin polymerization is essential for tumor progression and maintenance of tumor tissue integrity in a mutant Braf ; Pten loss driven mouse model for melanoma.
    • Effect of Education on Myopia: Evidence from the United Kingdom ROSLA 1972 Reform

      Plotnikov, D.; Williams, C.; Atan, D.; Davies, N.M.; Ghorbani Mojarrad, Neema; Guggenheim, J.A. (2020-09-04)
      Cross-sectional and longitudinal studies have consistently reported an association between education and myopia. However, conventional observational studies are at risk of bias due to confounding by factors such as socioeconomic position and parental educational attainment. The current study aimed to estimate the causal effect of education on refractive error using regression discontinuity analysis. Methods: Regression discontinuity analysis was applied to assess the influence on refractive error of the raising of the school leaving age (ROSLA) from 15 to 16 years introduced in England and Wales in 1972. For comparison, a conventional ordinary least squares (OLS) analysis was performed. The analysis sample comprised 21,548 UK Biobank participants born in a nine-year interval centered on September 1957, the date of birth of those first affected by ROSLA. Results: In OLS analysis, the ROSLA 1972 reform was associated with a −0.29 D (95% confidence interval [CI]: −0.36 to −0.21, P < 0.001) more negative refractive error. In other words, the refractive error of the study sample became more negative by −0.29 D during the transition from a minimum school leaving age of 15 to 16 years of age. Regression discontinuity analysis estimated the causal effect of the ROSLA 1972 reform on refractive error as −0.77 D (95% CI: −1.53 to −0.02, P = 0.04). Conclusions: Additional compulsory schooling due to the ROSLA 1972 reform was associated with a more negative refractive error, providing additional support for a causal relationship between education and myopia.
    • Preclinical Anticancer Activity of an Electron-Deficient Organoruthenium(II) Complex

      Soldevila-Barreda, Joan J.; Azmanova, Maria; Pitto-Barry, Anaïs; Cooper, Patricia A.; Shnyder, Steven D.; Barry, Nicolas P.E. (2020-06-04)
      Ruthenium compounds have been shown to be promising alternatives to platinum(II) drugs. However, their clinical success depends on achieving mechanisms of action that overcome Pt-resistance mechanisms. Electron-deficient organoruthenium complexes are an understudied class of compounds that exhibit unusual reactivity in solution and might offer novel anticancer mechanisms of action. Here, we evaluate the in vitro and in vivo anticancer properties of the electron-deficient organoruthenium complex [(p-cymene)Ru(maleonitriledithiolate)]. This compound is found to be highly cytotoxic: 5 to 60 times more potent than cisplatin towards ovarian (A2780 and A2780cisR), colon (HCT116 p53+/+ and HCT116 p53−/−), and non-small cell lung H460 cancer cell lines. It shows no cross-resistance and is equally cytotoxic to both A2780 and A2780cisR cell lines. Furthermore, unlike cisplatin, the remarkable in vitro antiproliferative activity of this compound appears to be p53-independent. In vivo evaluation in the hollow-fibre assay across a panel of cancer cell types and subcutaneous H460 non-small cell lung cancer xenograft model hints at the activity of the complex. Although the impressive in vitro data are not fully corroborated by the in vivo follow-up, this work is the first preclinical study of electron-deficient half-sandwich complexes and highlights their promise as anticancer drug candidates.
    • Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumour drug accumulation and limiting bioavailability and toxicity in normal tissues

      Ingram, N.; McVeigh, L.E.; Abou-Saleh, R.H.; Maynard, J.; Peyman, S.A.; McLaughlan, J.R.; Fairclough, M.; Marston, G.; Valleley, E.M.A.; Jimenez-Macias, J.L.; et al. (2020)
      Most cancer patients receive chemotherapy at some stage of their treatment which makes improving the efficacy of cytotoxic drugs an ongoing and important goal. Despite large numbers of potent anti-cancer agents being developed, a major obstacle to clinical translation remains the inability to deliver therapeutic doses to a tumor without causing intolerable side effects. To address this problem, there has been intense interest in nanoformulations and targeted delivery to improve cancer outcomes. The aim of this work was to demonstrate how vascular endothelial growth factor receptor 2 (VEGFR2)-targeted, ultrasound-triggered delivery with therapeutic microbubbles (thMBs) could improve the therapeutic range of cytotoxic drugs. Methods: Using a microfluidic microbubble production platform, we generated thMBs comprising VEGFR2-targeted microbubbles with attached liposomal payloads for localised ultrasound-triggered delivery of irinotecan and SN38 in mouse models of colorectal cancer. Intravenous injection into tumor-bearing mice was used to examine targeting efficiency and tumor pharmacodynamics. High-frequency ultrasound and bioluminescent imaging were used to visualise microbubbles in real-time. Tandem mass spectrometry (LC-MS/MS) was used to quantitate intratumoral drug delivery and tissue biodistribution. Finally, 89Zr PET radiotracing was used to compare biodistribution and tumor accumulation of ultrasound-triggered SN38 thMBs with VEGFR2 targeted SN38 liposomes alone. Results: ThMBs specifically bound VEGFR2 in vitro and significantly improved tumor responses to low dose irinotecan and SN38 in human colorectal cancer xenografts. An ultrasound trigger was essential to achieve the selective effects of thMBs as without it, thMBs failed to extend intratumoral drug delivery or demonstrate enhanced tumor responses. Sensitive LC-MS/MS quantification of drugs and their metabolites demonstrated that thMBs extended drug exposure in tumors but limited exposure in healthy tissues, not exposed to ultrasound, by persistent encapsulation of drug prior to elimination. 89Zr PET radiotracing showed that the percentage injected dose in tumors achieved with thMBs was twice that of VEGFR2-targeted SN38 liposomes alone. Conclusions: thMBs provide a generic platform for the targeted, ultrasound-triggered delivery of cytotoxic drugs by enhancing tumor responses to low dose drug delivery via combined effects on circulation, tumor drug accumulation and exposure and altered metabolism in normal tissues.
    • Dig! Arts Access Project: Finding Inspiration in the Park

      Giles, M.; Croucher, Karina T. (2019)
      Dig! Arts Access Project brought together excavation with artistic interpretations using collage, painting, drawing and poetry, to engage school learners in the legacy of the Whitworth Park Community Archaeology and History project. Through a series of workshops and site visits with local schools, participants expressed some of the ambiguities felt by urban children about parks. However, by the end of the sessions, they had increased their understanding of the history and heritage of their everyday places and were more confident about visiting parks.
    • Optimised patient information materials and recruitment to a study of behavioural activation in older adults: an embedded study within a trial

      Knapp, P.; Gilbody, S.; Holt, J.; Keding, A.; Mitchell, N.; Raynor, D.K.; Silcock, Jonathan; Torgerson, D. (2020-05-21)
      Printed participant information about randomised controlled trials is often long, technical and difficult to navigate. Improving information materials is possible through optimisation and user-testing, and may impact on participant understanding and rates of recruitment. Methods: A study within a trial (SWAT) was undertaken within the CASPER trial. Potential CASPER participants were randomised to receive either the standard trial information or revised information that had been optimised through information design and user testing. Results: A total of 11,531 patients were randomised in the SWAT. Rates of recruitment to the CASPER trial were 2.0% in the optimised information group and 1.9% in the standard information group (odds ratio 1.027; 95% CI 0.79 to 1.33; p=0.202). Conclusions: Participant information that had been optimised through information design and user testing did not result in any change to rate of recruitment to the host trial. Registration: ISRCTN ID ISRCTN02202951; registered on 3 June 2009.
    • Co-delivery of a RanGTP inhibitory peptide and doxorubicin using dual loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer cells

      Haggag, Y.; Abu Ras, Bayan; El-Tanani, Yahia; Tambuwala, M.M.; McCarron, P.; Isreb, Mohammed; El-Tanani, Mohamed (2020-09-15)
      Multidrug resistance (MDR) limits the beneficial outcomes of conventional breast cancer chemotherapy. Ras-related nuclear protein (Ran-GTP) plays a key role in these resistance mechanisms, assisting cancer cells to repair damage to DNA. Herein, we investigate the co-delivery of Ran-RCC1 inhibitory peptide (RAN-IP) and doxorubicin (DOX) to breast cancer cells using liposomal nanocarriers. A liposomal delivery system, co-encapsulating DOX, and RAN-IP, was prepared using a thin-film rehydration technique. Dual-loaded liposomes were optimized by systematic modification of formulation variables. Real-Time-Polymerase Chain Reaction was used to determine Ran-GTP mRNA expression. In vitro cell lines were used to evaluate the effect of loaded liposomes on the viability of breast and lung cancer cell lines. In vivo testing was performed on a murine Solid Ehrlich Carcinoma model. RAN-IP reversed the Ran-expression-mediated MDR by inhibiting the Ran DNA damage repair function. Co-administration of RAN-IP enhanced sensitivity of DOX in breast cancer cell lines. Finally, liposome-mediated co-delivery with RAN-IP improved the anti-tumor effect of DOX in tumor-bearing mice when compared to single therapy. This study is the first to show the simultaneous delivery of RAN-IP and DOX using liposomes can be synergistic with DOX and lead to tumor regression in vitro and in vivo.
    • Investigation of the role of VHL-HIF signaling in DNA repair and apoptosis in zebrafish

      Kim, H.R.; Santhakumar, K.; Markham, E.; Baldera, D.; Greenald, D.; Bryant, H.E.; El-Khamisy, Sherif F.; van Eeden, F.J. (2020-03)
      pVHL is a tumor suppressor. The lack of its function leads to various tumors, among which ccRCC (clear cell renal cell carcinoma) has the most serious outcome due to its resistance to chemotherapies and radiotherapies. Although HIF promotes the progression of ccRCC, the precise mechanism by which the loss of VHL leads to tumor initiation remains unclear. We exploited two zebrafish vhl mutants, vhl and vll, and Tg(phd3:: EGFP)i144 fish to identify crucial functions of Vhl in tumor initiation. Through the mutant analysis, we found that the role of pVHL in DNA repair is conserved in zebrafish Vll. Interestingly, we also discovered that Hif activation strongly suppressed genotoxic stress induced DNA repair defects and apoptosis in vll and brca2 mutants and in embryos lacking ATM activity. These results suggest the potential of HIF as a clinical modulator that can protect cells from accumulating DNA damage and apoptosis which can lead to cancers and neurodegenerative disorders.
    • Nucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cells

      Ivana, Barbaric,; Peter W, Andrews,; Halliwell, J.A.; Frith, T.J.R.; Laing, O.; Price, C.J.; Bower, O.J.; Stavish, T.; Gokhale, P.J.; Hewitt, Z.; et al. (2020-06-09)
      Human pluripotent stem cells (PSCs) are subject to the appearance of recurrent genetic variants on prolonged culture. We have now found that, compared with isogenic differentiated cells, PSCs exhibit evidence of considerably more DNA damage during the S phase of the cell cycle, apparently as a consequence of DNA replication stress marked by slower progression of DNA replication, activation of latent origins of replication, and collapse of replication forks. As in many cancers, which, like PSCs, exhibit a shortened G1 phase and DNA replication stress, the resulting DNA damage may underlie the higher incidence of abnormal and abortive mitoses in PSCs, resulting in chromosomal non-dysjunction or cell death. However, we have found that the extent of DNA replication stress, DNA damage, and consequent aberrant mitoses can be substantially reduced by culturing PSCs in the presence of exogenous nucleosides, resulting in improved survival, clonogenicity, and population growth.
    • Resolution of coronavirus disease 2019 (COVID-19)

      Habas, Khaled S.A.; Nganwuchu, C.; Shahzad, F.; Gopalan, Rajendran C.; Haque, M.; Rahman, Sayeeda; Majumder, A.A.; Nasim, T. (2020)
      Introduction. Coronavirus disease 2019 (COVID-19) was first detected in China in December, 2019, and declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. The current management of COVID-19 is based generally on supportive therapy and treatment to prevent respiratory failure. The effective option of antiviral therapy and vaccination are currently under evaluation and development. Areas covered. A literature search was performed using PubMed between December 1, 2019–June 23, 2020. This review highlights the current state of knowledge on the viral replication and pathogenicity, diagnostic and therapeutic strategies, and management of COVID-19. This review will be of interest to scientists and clinicians and make a significant contribution toward development of vaccines and targeted therapies to contain the pandemic. Expert Opinion. The exit strategy for a path back to normal life is required, which should involve a multi-prong effort toward development of new treatment and a successful vaccine to protect public health worldwide and prevent future COVID-19 outbreaks. Therefore, the bench to bedside translational research as well as reverse translational works focusing bedside to bench is very important and would provide the foundation for the development of targeted drugs and vaccines for COVID-19 infections.
    • A massive, Late Neolithic pit structure associated with Durrington Walls Henge

      Gaffney, Vincent L.; Baldwin, E.; Bates, M.; Bates, C.R.; Gaffney, Christopher F.; Hamilton, D.; Kinnaird, T.; Neubauer, W.; Yorston, R.; Allaby, R.; et al. (2020-06)
      A series of massive geophysical anomalies, located south of the Durrington Walls henge monument, were identified during fluxgate gradiometer survey undertaken by the Stonehenge Hidden Landscapes Project (SHLP). Initially interpreted as dewponds, these data have been re-evaluated, along with information on similar features revealed by archaeological contractors undertaking survey and excavation to the north of the Durrington Walls henge. Analysis of the available data identified a total of 20 comparable features, which align within a series of arcs adjacent to Durrington Walls. Further geophysical survey, supported by mechanical coring, was undertaken on several geophysical anomalies to assess their nature, and to provide dating and environmental evidence. The results of fieldwork demonstrate that some of these features, at least, were massive, circular pits with a surface diameter of 20m or more and a depth of at least 5m. Struck flint and bone were recovered from primary silts and radiocarbon dating indicates a Late Neolithic date for the lower silts of one pit. The degree of similarity across the 20 features identified suggests that they could have formed part of a circuit of large pits around Durrington Walls, and this may also have incorporated the recently discovered Larkhill causewayed enclosure. The diameter of the circuit of pits exceeds 2km and there is some evidence that an intermittent, inner post alignment may have existed within the circuit of pits. One pit may provide evidence for a recut; suggesting that some of these features could have been maintained through to the Middle Bronze Age. Together, these features represent a unique group of features related to the henge at Durrington Walls, executed at a scale not previously recorded.
    • Additive Manufacturing of a Point-of-Care “Polypill:” Fabrication of Concept Capsules of Complex Geometry with Bespoke Release against Cardiovascular Disease

      Pereira, B.C.; Isreb, Abdullah; Isreb, Mohammad; Forbes, R.T.; Oga, E.F.; Alhnan, M.A. (2020-07)
      Polypharmacy is often needed for the management of cardiovascular diseases and is associated with poor adherence to treatment. Hence, highly flexible and adaptable systems are in high demand to accommodate complex therapeutic regimens. A novel design approach is employed to fabricate highly modular 3D printed “polypill” capsules with bespoke release patterns for multiple drugs. Complex structures are devised using combined fused deposition modeling 3D printing aligned with hot-filling syringes. Two unibody highly modular capsule skeletons with four separate compartments are devised: i) concentric format: two external compartments for early release while two inner compartments for delayed release, or ii) parallel format: where nondissolving capsule shells with free-pass corridors and dissolution rate-limiting pores are used to achieve immediate and extended drug releases, respectively. Controlling drug release is achieved through digital manipulation of shell thickness in the concentric format or the size of the rate limiting pores in the parallel format. Target drug release profiles are achieved with variable orders and configurations, hence confirming the modular nature with capacity to accommodate therapeutics of different properties. Projection of the pharmacokinetic profile of this digital system capsules reveal how the developed approach can be applied in dose individualization and achieving multiple desired pharmacokinetic profiles.
    • The assessment of intramolecular hydrogen bonding in ortho-substituted anilines by an NMR method

      Abraham, M.H.; Abraham, R.J.; Aghamohammadi, Amin; Afarinkia, Kamyar; Liu, Xiangli (2020-10-01)
      We describe the Δlog P method for the assessment of intramolecular hydrogen bonds (IMHBs), and show that it is not a very general method of distinguishing between molecules in which there is an IMHB and molecules in which there is no IMHB. The ‘double’ Δlog P method of Shalaeva et al. is a much more reliable method for the assessment of IMHB but requires the synthesis of a model compound and the determination of no less than four water-solvent partition coefficients. In addition, it is difficult to apply to compounds that contain more than one hydrogen bond acidic group capable of IMHB. We then describe our NMR method of assessing IMHB, based on 1H NMR chemical shifts in solvents DMSO and CDCl3. We have determined 1H NMR chemical shifts for a number of ortho-substituted anilines and show that the only compound we have studied that forms an IMHB is methyl 2-methylaminobenzoate though there is no IMHB present in methyl 2-aminobenzoate. This apparently anomalous result is supported by both MM and ab initio calculations. The NMR method is much simpler and less time consuming than other methods for the assessment of IMHB. It provides a quantitative assessment of IMHB and can be applied to molecules with more than one hydrogen bond acidic group.
    • (3S)-3-(2,3-difluorophenyl)-3-methoxypyrrolidine (IRL752) - a novel cortical-preferring catecholamine transmission- and cognition-promoting agent

      Hjorth, S.; Waters, S.; Waters, N.; Tedroff, J.; Svensson, P.; Fagerberg, A.; Edling, M.; Svanberg, B.; Ljung, E.; Gunnergren, J.; et al. (2020-09)
      Here we describe for the first time the distinctive pharmacological profile for IRL752, a new phenyl-pyrrolidine derivative with regio-selective CNS transmission-enhancing properties. IRL752 (3.7-150 μmol/kg, s.c.) was characterised through extensive in vivo studies, using behavioural, tissue neurochemical and gene expression, as well as microdialysis methods. Behaviourally, the compound normalised tetrabenazine-induced hypoactivity, while unable to stimulate basal locomotion in normal animals or to either accentuate or reverse hyperactivity induced by amphetamine or MK-801. IRL752 induced but minor changes in monoaminergic tissue neurochemistry across NA- and DA-dominated brain regions. The expression of neuronal activity-, plasticity-, and cognition-related IEGs (immediate early genes) however increased by 1.5- to 2-fold. Furthermore, IRL752 dose-dependently enhanced cortical catecholamine dialysate output to 600-750% above baseline, while striatal DA remained unaltered and NA rose to ~250%; cortical and hippocampal dialysate ACh increased to ~250% and 190% above corresponding baseline, respectively. In line with this cortically preferential transmission-promoting action, the drug was also pro-cognitive in the novel object recognition and reversal learning tests. In vitro neurotarget affinity and functional data, coupled to drug exposure support the hypothesis that 5‑HT7 receptor and α2(C)-adrenoceptor antagonism are key contributors to the in vivo efficacy and original profile of IRL752. The cortical-preferring facilitatory impact on catecholamine (and ACh) neurotransmission, along with effects on IEG expression and cognition-enhancing features, are in line with the potential clinical usefulness of IRL752 in conditions where these aspects may be dysregulated, such as in axial motor and cognitive deficits in Parkinson's Disease.
    • Multi-Proxy Characterisation of the Storegga Tsunami and Its Impact on the Early Holocene Landscapes of the Southern North Sea

      Gaffney, Vincent L.; Fitch, Simon; Bates, M.; Ware, R.L.; Kinnaird, T.; Gearey, B.; Hill, T.; Telford, Richard; Batt, Catherine M.; Stern, Ben; et al. (2020-07-15)
      Doggerland was a landmass occupying an area currently covered by the North Sea until marine inundation took place during the mid-Holocene, ultimately separating the British landmass from the rest of Europe. The Storegga Event, which triggered a tsunami reflected in sediment deposits in the northern North Sea, northeast coastlines of the British Isles and across the North Atlantic, was a major event during this transgressive phase. The spatial extent of the Storegga tsunami however remains unconfirmed as, to date, no direct evidence for the event has been recovered from the southern North Sea. We present evidence of a tsunami deposit in the southern North Sea at the head of a palaeo-river system that has been identified using seismic survey. The evidence, based on lithostratigraphy, geochemical signatures, macro and microfossils and sedimentary ancient DNA (sedaDNA), supported by optical stimulated luminescence (OSL) and radiocarbon dating, suggests that these deposits were a result of the tsunami. Seismic identification of this stratum and analysis of adjacent cores showed diminished traces of the tsunami which was largely removed by subsequent erosional processes. Our results confirm previous modelling of the impact of the tsunami within this area of the southern North Sea, and also indicate that these effects were temporary, localized, and mitigated by the dense woodland and topography of the area. We conclude that clear physical remnants of the wave in these areas are likely to be restricted to now buried, palaeo-inland basins and incised river valley systems.
    • Synthesis and Characterization of Novel Nopyl-Derived Phosphonium Ionic Liquids

      Yu, Jiangou; Wheelhouse, Richard T.; Honey, M.A.; Karodia, N. (2020-10-10)
      A series of novel nopyl-derived chiral phosphonium ionic liquids have been successfully synthesised and characterised. Analysis of each novel ionic liquid was conducted in order to confirm structure, purity and thermal stability.
    • Intriguing High Z'' Cocrystals of Emtricitabine

      Palanisamy, V.; Sanphui, P.; Bolla, G.; Narayan, Aditya; Seaton, Colin C.; Vangala, Venu R. (Crystal Growth & Design, 2020-08)
      Emtricitabine (ECB) afforded dimorphic cocrystals (Forms I, II) of benzoic acid (BA), whereas with p-hydroxybenzoic acid (PHBA), p-aminobenzoic acid (PABA) are resulted in as high Z'' cocrystals. Intriguingly, the Z'' of cocrystals are trends from two to fourteen based on the manipulation of functional groups on the para position of BA (where H atom is replaced with that of OH or NH2 group). ECB‒PABA cocrystal consists of six molecules each and two water molecules in the asymmetric unit (Z''=14) with 2D planar sheets represents the rare pharmaceutical cocrystal. The findings suggest that the increment of H bond donor(s) systematically via a suitable coformer are in correspondence with attaining high Z'' cocrystals. Further, solid state NMR spectroscopy in conjunction with single crystal X-ray diffraction are demonstrated as significant tools to enhance the understanding of the number of symmetry independent molecules in the crystalline lattice and provide insights to the mechanistic pathways of crystallization.
    • Technological, Refitting and Microwear of the Stone Artefact Assemblage

      Pope, M.; Davis, R.; Evans, Adrian A. (SpoilHeap, 2020-08)