The preparation of a series of oligomeric engineering thermoplastics (PS, PES, PEI and PAI) is reported. H and C NMR and FT-IR/ATR spectroscopic techniques are combined to determine the chemical structure of the synthetic polymers, which are produced in good yield and purity. GPC measurements show the weight average molecular weight (M ) of the synthesised thermoplastics fall in the range 5454-33,866 g mol and display polydispersity indices in the range 1.33-1.82. Glass transition temperatures (T) values measured by DSC, occur between 107 and 257 °C and fall in the pattern PS
Hamerton I, Howlin BJ, Yeung S-YC (2013) Designing thermoplastic oligomers with programmed degradation mechanisms using a combined empirical and simulation approach, Polymer Degradation and Stability 98 (4) pp. 829-838
Molecular simulation is used to probe the structure property relationships displayed by polysulphone (PS) and polyethersulphone (PES) and reproduces closely the temperatures at which thermal degradation occurs (and the glass transition temperatures). Both data sets agree well with those obtained empirically using TGA. The examination of the thermal and thermo-oxidative stability of thermoplastic oligomers (M = 5454-33,866 g mol , PDI 1.33-1.82) based on PS, PES, polyetherimide (PEI) and poly(amide-imide) (PAI), is reported. TGA reveals the least thermally stable polymer is PES (T =
The p22phox is a key component of the cytochrome b558 of the NADPH oxidase (Nox), which by generating reactive oxygen species (ROS) is involved in the pathogenesis of cardiovascular disease. A p22phox polymorphism (C242T) has been found to reduce oxidative stress in the cardiovascular system and is negatively associated with the incidence of coronary heart disease (CHD). However, the mechanism involved remains unknown. In this study we used computer molecular modelling and bioinformatics to investigate the potential effect of C242T polymorphism on the 3-D protein structure of the p22phox. Based on the published sequence data of p22phox and the principle of regulated prediction algorithms, we found that p22phox consists of two domains: an N-terminal transmembrane domain (124 a.a.) and a C-terminal cytoplasmic domain (71 a.a.). In its most stable form, it has three e26 Heart September 2010 Vol 96 No 17 BSCR Spring 2010 Meeting Abstracts Downloaded from heart.bmj.com on January 31, 2012 - Published by group.bmj.com transmembrane helices leading to an extracellular N-terminus and an extracellular loop between helices two and three. The C242T polymorphism causes a change of His72 to Tyr72. This change results in significant morphological changes of the extracellular loop of the p22phox, which is in the putative interactive region of the p22phox with the catalytic subunit (Nox2). This may interfere with their association, and subsequently result in a reduced cytochrome b function and a reduced ROS production by NADPH oxidase. These results give us insight into the molecular mechanism of this polymorphism in reducing vascular oxidative stress and may explain how this polymorphism is linked with reduced incidence of CHD.
Palmer RA, Ladd M, Howlin B, Lisgarten DR (2013) X-ray structures of two forms of the antibiotic oligomycin A: An inhibitor of ATP synthase, Future Medicinal Chemistry 5 (8) pp. 881-893
Background: Corrections to the chemical and x-ray structures of two forms of the antibiotic oligomycin A are presented: the original and best known, form (E), from Streptomyces diastatochromogenes, and a new form (C) from Streptomyces diastaticus. Method: The crystal structures are isomorphous, crystallizing in space group P222, with Z = 4[C HO.CHOH] per unit cell. Oligomycin A(E) refined with R1 = 0.0734, using Cu K± x-radiation; and for Oligomycin A(C) R1 = 0.0651 using Mo K± x-radiation. Conclusion: Serious corrections to the previously published structure of oligomycin A(C) are discussed and implemented. As a supplementary study geometry optimization of side group R4 of oligomycin A(E) was undertaken and achieved by energy minimization. These additional results clearly confirm the delocalization in this region observed in both x-ray structures. This result is contrary to the generally accepted formulation. Knowledge of the correct structures is important to those involved in the study and applications of the pharmacological and biological properties of these materials. © 2013 Future Science Ltd.
Hamerton I, Aspin I P, Howlin B J, Jones J R, Parker M J (1997) Kinetic and computer modelling of epoxy resin cure, Proceedings of the Conference on Epoxy Technologies for Ambient Cure Protective Coatings (1)
Lockley WJS, Sfyrakis K, Howlin BJ, Jones JR, Wilkinson DJ (2007) Some IT and data processing applications for 2H, 3H,11C,13C and 14C-labelling, Journal of Labelled Compounds and Radiopharmaceuticals 50 (5-6) pp. 532-534
Hamerton I, Hamerton I, McNamara LT, Howlin BJ, Smith PA, Cross P, Ward S (2014) Developing toughened aromatic polybenzoxazines using thermoplastic oligomers and telechelics, part 1: Preparation and characterization of the functionalized oligomers, Journal of Applied Polymer Science 131 (19)
The preparation and characterization of three families of thermoplastic oligomers (Mn0=02918-13263 g mol-1) based on polyarylsulfone (PSU) differing in both molecular weight and terminal functionality and one series of polyarylethersulfone (PES) of different molecular weights is reported. Infrared and nuclear magnetic resonance spectroscopy data support the formation of both the hydroxyl terminated oligomers and conversion (67-89% depending on molecular weight) to the telechelic PSU oligomer bearing reactive benzoxazine groups. Differential scanning calorimetry reveals that the onset of homopolymerization in the telechelic PSU oligomer occurs at around 100°C (peak maximum 125°C at 10 K/min) and rescans show values of the glass transition (for the homopolymers) ranging from 124 to 167°C depending on molecular weight. The influence on the oligomer backbone and terminal functionality is examined using thermal analysis. © 2014 Wiley Periodicals, Inc.
A series of copoly(methoxy-thiocyanurate)s is prepared in good yield and purity, and fully characterised. Many of the resulting polymers, formed at room temperature using phase transfer catalysis, can be cast into films with good resilience and thermal stability (some examples suffer practically no mass loss when held isothermally at 190 °C and only display appreciable losses when held continuously at 225 °C). Char yields of 61-64% are achieved in nitrogen depending on backbone structure. Some problems were encountered with solubility, particularly with copolymers, which limited molecular weights analysis, but values of Mn = 7000-10,000 g mol-1 were obtained for the polycyanurate and polythiocyanurate homopolymers. DSC reveals polymerisation exotherms with maxima at 197-207 °C (Hp = 39-48 kJ/mol), which are believed to be due to isomerisation of the (activation energies span 172-205 kJ/mol), since X-ray powder diffraction measurements reveal no evidence of crystalline structure in the resulting product.
Two series of terpoly(methoxy-cyanurate-thiocyanurate)s based on thiodiphenol and dithiodiphenyl sulphide, and dihydroxydiphenylether and dithiodiphenyl ether, are prepared in good yield and purity, and fully characterised. Most of the resulting polymers, formed at room temperature using phase transfer catalysis, can be cast into films with good resilience and thermal stability. Two series of terpoly(methoxy-cyanurate-thiocyanurate)s based on thiodiphenol and dithiodiphenyl sulfide and on dihydroxydiphenyl ether and dithiodiphenyl ether, were prepared in good yield and purity and fully characterized. Most of the resulting polymers, formed at room temperature using phase transfer catalysis, can be cast into films with good resilience and thermal stability (some examples suffer practically no mass loss when held isothermally at 190 °C and only display appreciable losses when held continuously at 225 °C). Char yields of 53%-61% are achieved in nitrogen depending on backbone structure. Some problems were encountered with solubility, particularly with copolymers, which limited molecular weight analysis, but values of Mn = 8000-13000 g mol-1 were obtained for the polymers based on thiodiphenol and dithiodiphenyl sulfide, and Mn = 5000-13000 g mol-1 for the polymers based on dihydroxydiphenyl ether and dithiodiphenyl ether. DSC reveals polymerization exotherms with maxima at 184-207 °C (Hp = 43-59 kJ mol-1), which are believed to be due to isomerization of the cyanurate to the isocyanurate (activation energies span 159-195 kJ mol-1). Molecular simulation shows that diphenylether and diphenylsulfide display very similar conformational energy surfaces and would therefore be expected to adopt similar conformations, but the diphenylsulfide offers less resistance to deformations that increase the proximity of the two phenyl rings and results in more resilient films. © 2013 Society of Chemical Industry.
Three cyanate ester monomer or oligomer species: 2,2-bis(4-cyanatophenyl)propane 1, 1-1-bis(4-dicyanatophenyl)ethane 2, and the oligomeric phenolic cyanate 3, are blended in various ratios to form binary mixtures (18 in total), formulated with copper(II) acetylacetonate (200 ppm) in dodecylphenol (1 % w/v active copper suspension) and cured (3 Kmin-1 to 150 °C + 1 hour; 3 Kmin-1 to 200 °C + 3 hours) followed by a post cure (3 Kmin-1 to 260 °C + 1 hour). Cured copolymers were exposed to environments of elevated relative humidity (75 % RH) and parallel immersion testing in H2O, H2SO4 (10 %) and NaOH (10 %) at 25 °C for a period of up to 2 years and accelerated ageing in boiling water (14 days). Periodic measurements are made of moisture gain along with infrared spectra and compared with cured homopolymers. Changes in mass are recorded periodically throughout exposure, prior to destructive thermo-mechanical analyses. Dynamic mechanical thermal analysis data comparing neat and exposed blends demonstrate the detrimental effect of moisture ingress whilst data from thermogravimetric analysis demonstrate no change in degradation onset between neat and exposed materials. An optimised blend of 1:1 of monomer units 1 and 2 was found to absorb less moisture than blends of different stoichiometry or between other respective monomeric units, consequently limiting the deleterious effect of moisture ingress.
The synthesis and characterisation of a partially substituted calixarene, namely, 5,11,17,23- tetra-tert-butyl,25,27-bis[aminoethoxy] 26,28-dihydroxycalixarene are reported. Its interaction with commonly used pharmaceuticals (clofibric acid, diclofenac and aspirin) was investigated by spectroscopic (1 H NMR and UV), electrochemical (conductance measurements) and thermal (titration calorimetry) techniques. It is concluded on the basis of the experimental work and molecular simulation studies that the receptor interacts selectively with these drugs. Preliminary studies on the selective extraction of these pharmaceuticals from water by the calix receptor are reported and the potential for a carrier mediated sensor based on this ligand for ?on site? monitoring of pharmaceuticals is discussed.
This study uses the Molecular Operating Environment software (MOE) to generate models to calculate the char yield of polybenzoxazines (PBz). A series of benzoxazine (Bz) monomers were constructed to which a variety of parameters relating to the structure (e.g., water accessible surface, negative van der Waals surface area and hydrophobic volume, etc.) were obtained and a quantitative structure property relationships (QSPR) model was generated. The model was used to generate data for new Bz monomers with desired properties and a comparison was made of predictions based on the QSPR model with the experimental data. This study shows the quality of predictive models and confirms how useful computational screening is prior to synthesis.
Lisgarten D, Palmer R, Lobley C, Naylor C, Chowdhry B, Al?Kurdi Z, Badwan A, Howlin BJ, Gibbons N, Saldanha J, Lisgarten J, Basak A (2017) Ultra?high resolution X?ray structures of two forms of human recombinant insulin at 100 K, Chemistry Central Journal 11 (73)
The crystal structure of a commercially available form of human recombinant (HR) insulin, Insugen (I), used in the treatment of diabetes has been determined to 0.92 Å resolution using low temperature, 100 K, synchrotron X-ray data collected at 16,000 keV (» = 0.77 Å). Refinement carried out with anisotropic displacement parameters, removal of main-chain stereochemical restraints, inclusion of H atoms in calculated positions, and 220 water molecules, converged to a final value of R = 0.1112 and Rfree = 0.1466. The structure includes what is thought to be an ordered propanol molecule (POL) only in chain D(4) and a solvated acetate molecule (ACT) coordinated to the Zn atom only in chain B(2). Possible origins and consequences of the propanol and acetate molecules are discussed. Three types of amino acid representation in the electron density are examined in detail: (i) sharp with very clearly resolved features; (ii) well resolved but clearly divided into two conformations which are well behaved in the refinement, both having high quality geometry; (iii) poor density and difficult or impossible to model. An example of type (ii) is observed for the intra-chain disulphide bridge in chain C(3) between S³6?S³11 which has two clear conformations with relative refined occupancies of 0.8 and 0.2, respectively. In contrast the corresponding S?S bridge in chain A(1) shows one clearly defined conformation. A molecular dynamics study has provided a rational explanation of this difference between chains A and C. More generally, differences in the electron density features between corresponding residues in chains A and C and chains B and D is a common observation in the Insugen (I) structure and these effects are discussed in detail. The crystal structure, also at 0.92 Å and 100 K, of a second commercially available form of human recombinant insulin, Intergen (II), deposited in the Protein Data Bank as 3W7Y which remains otherwise unpublished is compared here with the Insugen (I) structure. In the Intergen (II) structure there is no solvated propanol or acetate molecule. The electron density of Intergen (II), however, does also exhibit the three types of amino acid representations as in Insugen (I). These effects do not necessarily correspond between chains A and C or chains B and D in Intergen (II), or between corresponding residues in Insugen (I). The results of this comparison are reported.
Molecular Operating Environment (MOE) software has great potential when combined with the Quantitative
Structure-Property Relationship (QSPR) approach, and was proven to be useful to make good prediction models
for series of polybenzoxazines [1?3]. However, the effect of heterogeneities in the crosslinked network to the
prediction accuracy is yet to be tested. It was found that polybenzoxazines with polymerisable functional group
(e.g. acetylene-based benzoxazines) form up to 40% higher char yield compared to their analogue polybenzoxazines
due to the contribution of the polymerisable functional group (e.g. ethynyl triple bond) in the
cross-linked network. In order to investigate the effect of the inconsistent cross-linking network, a data set
consisting of thirty-three benzoxazines containing various structures of benzoxazines was subdivided into two
smaller data sets based on their functional group, either benzoxazines with polymerisable functional group
(acetylene-based benzoxazines set (Ace-M)) or non-polymerisable functional group (aniline-based benzoxazines
(Ani-M)). Char yield predictions for the polybenzoxazines for these data sets (Ace-M and Ani-M) were compared
with the larger thirty-three polybenzoxazines data set (GM) to investigate the effect of the inconsistency in
crosslink network on the quality of prediction afforded by the model. Prediction performed by Ace-M and Ani-M
were found to be more accurate when compared with the GM with total prediction error of 3.15% from both
models compared to the GM (4.81%). Ace-M and Ani-M are each better at predicting the char yields of similar
polybenzoxazines (i.e. one model is specific for a polymerisable functional group; the other for non-polymerisable
functional group), but GM is more practical as it has greater ?general? utility and is applicable to
numerous structures. The error shown by GM is considerably small and therefore it is still a good option for
prediction and should not be underestimated.
The mechanism of reaction between 1-ethyl-3-methylimidazolium acetate and the
difunctional diglycidyl ether of bisphenol A (DGEBA) is explored using thermal and spectroscopic
methods. Investigation of the 1,3-dialkylimidazolium based ionic liquids comprising the common
cation (1-ethyl-3-methylimidazolium) and different anions (acetate, diethyl phosphate, dicyanamide
or thiocyanate) via thermogravimetric analysis revealed 1-ethyl-3-methylimidazolium acetate to be
the least thermally stable, both in air and nitrogen, and 1-ethyl-3-methylimidazolium dicyanamide
to be the most thermally stable. Dynamic differential scanning calorimetry reveals the formulations
comprising DGEBA and ionic liquid where it was revealed that the lowest and highest temperature
for the onset of reaction were observed for formulations with 1-ethyl-3-methylimidazolium acetate
and 1-ethyl-3-methylimidazolium dicyanamide respectively. 1-Ethyl-3-methylimidazolium acetate
was shown, via nuclear magnetic resonance (NMR) spectroscopy and residual gas analysis, to
degrade at 150 °C to yield dealkylated products including methyl acetate and ethyl acetate as well
as 1-methylimidazole and 1- ethylimidazole. The dealkylated imidazole ring is proposed as a route
for initiation of the epoxy ring. Adduct formation between 1-ethyl-3-methylimidazoloium acetate
and benzaldehyde at room temperature was observed leading to the proposal of the generation of a
carbene species as a route for initiation of the epoxy ring in formulations with the acetate anion.
NMR analysis of formulations comprising 1-ethyl-3-methylimidazolium thiocyanate and epoxy are
believed, at room temperature, to initiate via reaction of the thiocyanate anion with the epoxy ring.At elevated temperatures, it is proposed that a second, competing reaction, involving deprotonation
of the imidazolium ring, also becomes active. The three proposed reaction pathways, namely the
carbene route, the imidazole route and the counter-ion route, are all proposed to occur when an
ionic liquid is used to initiate an epoxy resin.
Wet processes of phosphoric acids produce untreated wastewater containing large amounts of fluoride leading to serious environmental problems. This paper reports fundamental studies on two lower rim functionalised calixarene based receptors namely 5, 11, 17, 23 tetra-tert-butyl, 25, 27 bis [diethylphenylurea]ethoxy, 26, 28 dihydroxycalixarene, 1 and 25, 27 bis[diethylphenylurea]ethoxy, 26, 28 dihydroxycalixarene, 2 and their ionic interactions. It is shown that these receptors only interact with fluoride and phosphate in acetonitrile. Their receptive properties are higher for phosphate (2:1 anion:receptor complex) relative to fluoride (1:1 complex).However thermodynamics shows that these receptors are more selective for fluoride relative to phosphate in the formation of the 1:1 complex. The pathway from fundamental studies to the use of these receptors for removing these anions from water has been tested. The receptive properties of 1 for phosphate are held when the extraction involves aqueous solutions containing individual ions. However in mixtures containing both anions, the kinetics of the process and the selectivity of 1 for fluoride predominate and as a result, fluoride is better extracted than phosphate. The counter-ion effect on the removal process is assessed from Molecular Simulation studies. The removal of fluoride from phosphate is discussed taking into account existing technologies.
A commercial diglycidyl ether of bisphenol A monomer (Baxxores" ER 2200, eew 182/g/mole, DGEBA) is thermally polymerized in the presence of an ionic liquid, 1-ethyl-3-methylimidazolium acetate at a variety of loadings (5?45/wt %). The loss modulus data for cured samples, containing 5/wt % initiator, display at least two thermal transitions and the highest storage modulus occurs in the sample that has been cured for the shortest time at the lowest temperature. Samples that are exposed to higher temperatures (140, 150/°C) yield more heterogenous networks, whereas following exposure to a much shorter/lower temperature cure schedule (80/°C) exhibits a considerably higher damping ability than the other samples, coupled with a lower glass transition temperature. Differential scanning calorimetry reveals that the latter sample achieves a conversion of 95%, while crosslink densities for the DGEBA samples containing 5/wt % and 15/wt % are respectively 9.5/×/10-3/mol./dm-3 and 1.2/×/10-3/mol./dm-3 (when cured to 80/°C) and 2.0/×/10-2/mol./dm-3 and 2.4/×/10-3/mol./dm-3 (when cured to 140/°C).
The degradation behaviour of five polybenzoxazines (PBZs) is studied using pyrolysis-GC/MS. Upon heating to 800/°C in helium the PBZs generate a variety of similar pyrolysis products including aniline (the major product in all cases), substituted phenols, acridine, and 9-vinylcarbazole. During the initial stages of heating (200?300/°C) aniline is the dominant pyrolysis product; from 350/°C onwards substituted phenols are released, particularly 2-methylphenol and 2,6-dimethyl phenol. The same major species are produced on heating in air, but in addition isocyanatobenzene is observed which results from the oxidation of Mannich bridges, along with a number of sulphurous species from the monomer containing a thioether bridge. This suggests that sulphur is more likely to be retained in the char in a helium atmosphere, but takes part in oxidative reactions to form pyrolysis fragments in air. During the ramped temperature cycles in both air and helium atmospheres the release of aniline was observed to rise, fall and then to rise again. This may be due a combination of the very high heating rate, poor thermal conduction of the polymer and the availability of the Mannich bridges to undergo breakdown.
Four structurally related ionic liquids (1-ethyl-3-methylimidazolium acetate, 1-ethyl-3-methylimidazolium diethyl phosphate, 1-ethyl-3-methylimidazolium dicyanamide, and 1-ethyl-3-methylimidazolium thiocyanate) are examined for their storage characteristics and its effect on their ability to initiate the cure of epoxy resins. At ambient temperature, epoxy formulations containing 1-ethyl-3-methylimidazolium acetate and 1-ethyl-3-methylimidazolium thiocyanate display marked colour changes to yield dark red samples with greatly increased viscosity after one day; after six days both samples have undergone vitrification. The epoxy formulation containing 1-ethyl-3-methylimidazolium acetate continued to polymerise even at sub-zero temperatures. Storage in dark bottles retarded the reaction during the 30-minute period that the sample is removed from the freezer prior to an aliquot being taken, but once the autocatalytic low temperature reaction has started, the dark glass no longer provides effective protection. Samples of 1-ethyl-3-methylimidazolium dicyanamide/epoxy were also stored and sampled in the same manner, but no differences were exhibited between the samples in clear and dark brown glass bottles. Infrared and nuclear magnetic resonance studies confirmed that the hygroscopic ionic liquids pick up water readily (coordinating to the H atom at the 2-position on the imidazolium ring), but once dried the initiating ability is lost.
For the first time we present nanoindentation analysis of charred, cured aromatic cyanate esters, which
exhibit outstanding mechanical properties when analysed under applied loads of 0.1?300 mN. Following
charring (900 C for 10 minutes to achieve graphitised structures), the samples display a remarkable
combination of a modulus of elasticity of around 25 GPa and nanohardness of 300 kgf mm2, making
them some 30?40% stiffer than bone and practically as hard as tooth enamel. At the same time we find
that under the same conditions the chars are highly resilient, displaying complete elastic recovery with
very little plastic deformation. When cured in the presence of copper(II) acetylacetonate (200 ppm) in
dodecylphenol (1% w/v active copper suspension) to form a polycyanurate, compound (2) forms a dense,
consolidated structure compared with compound (1) under the same conditions. At high magnification,
the presence of a nanoscale, fibrillar structure is observed, accounting for the high resilience.
This study uses Molecular Operating Environment (MOE) to generate models to calculate the char yield of polybenzoxazines. A series of benzoxazine monomers were constructed to which a variety of parameters relating to the structure (e.g. water accessible surface, negative van der Waals surface area and hydrophobic volume, etc.) were obtained and a quantitative structure property relationships (QSPR) model was generated. The model was used to generate data for a new benzoxazine monomer and a comparison was made of predictions based on the QSPR models with the experimental data. This study shows the quality of predictive models and confirms how useful computational screening is prior to synthesis.
In order to do that, the QSPR models were tested over a series of internal and external validation tests to explore their internal and external predictivity, prior to experimental validations which were performed later and reported in Chapter 7. The internal and external validations found out that the discrepancy in the general model (GM) which was initially thought to be a drawback to the model?s performance was actually not, as it does not compromise the model?s prediction accuracy, both internally and externally. The validation process also found that one of the structure-specific models, Ph-M (aniline-based benzoxazines) is externally predictive whilst another structure-specific model, the Ace-M (acetylenic-based polybenzoxazines) is not internally and externally predictive due to the too small training set that affects its predictivity performance.
An acetylenic-based polybenzoxazine, poly(BA-apa) and a benzylamine-based polybenzoxazine, poly(BO-ba) have been successfully synthesised in this work. Both materials have been characterised using Fourier Transform ? Infra Red Spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR) spectroscopy (both 1H and 13C) and Liquid Chromatography-Mass Spectrometry (LC-MS) to confirm their structures. These materials were analysed using Differential Scanning Calorimetry (DSC) to study their polymerisation behaviour and were later cured and taken further to Thermogravimetric Analysis (TGA) in order to investigate their thermal properties and the amount of char yield formed upon heating at 800 oC under an inert (nitrogen) atmosphere ? which then will be used for experimental validation of the QSPR models.
The study of DSC thermograms showed that both polymers exhibit a distinct polymerisation behaviour e.g. BA-apa went through two polymerisation reactions simultaneously (the oxazine ring opening polymerisation and the acetylene addition reaction) whilst BO-ba only polymerised via the ring opening reaction from the oxazine rings. It was also found that BA-apa has a lower polymerisation activation energy, consistent to its lower polymerisation temperature in comparison to the BO-ba.
TGA analysis revealed that poly(BO-ba) formed an average of 44.35 % char yield and poly(BA-apa) on the other hand formed approximately 10 % higher char which is 56.28 %. The analysis also discovered that poly(BA-apa) synthesised in this work formed 15 % less char yield than previously reported in the literature (56.28 % vs. 71 %1) due to the shorter curing schedule. The final QSPR validation which is the experimental validation found that the char yield of poly(BO-ba) was predicted very well within 5-7 % error by both GM model and Ph-M. Ace-M which was reported earlier as not internally and externally predictive, has made a nearly accurate prediction towards the char yield of poly(BA-apa), close to the literature value of 71 %. The GM model has also made a close prediction to the Ace-M model, but these predictions deviated 15-17 % from the experimental poly(BA-apa) char yield measured in this work.
A series of commercial difunctional benzoxazine monomers are characterised carefully using thermal and thermo-mechanical techniques before constructing representative polymer networks using molecular simulation techniques. Good agreement is obtained between replicate analyses and for the kinetic parameters obtained from differential scanning calorimetry data (and determined using the methods of Kissinger and Ozawa). Activation energies range from 85-108 kJ/mol (Kissinger) and 89-110 kJ/mol (Ozawa) for the uncatalysed thermal polymerisation reactions, which achieve conversions of 85-97 %. Glass transition temperatures determined from differential scanning calorimetry and dynamic mechanical thermal analysis are coomparable, ranging from BA-a (151 °C, crosslink density 3.6 x 10-3 mol cm-3) containing the bisphenol A moiety to BP-a, based on a phenolphthalein bridge (239-256 °C, crosslink density 5.5-18.4 x 10-3 mol cm-3, depending on formulation). Molecular dynamics simulations of the polybenzoxazines generally agree well with empirical data, indicating that representative networks have been modelled.
A series of adducts were prepared based on the reaction of 1-ethyl-3-methylimidazolium acetate and benzal-
dehyde in various stoichiometries (from equimolar reaction to benzaldehyde in 10-fold excess) and the resulting
adducts were characterized using nuclear magnetic resonance spectroscopy (¹H, ¹³C, DEPT, and HQSC experi-
ments). Differential scanning calorimetry was used to examine the initiating behaviour of the adducts towards
mono- and di-functional epoxy resins and the data were used to determine kinetic parameters for the poly-
merization. The lower temperature peak, due to carbene formation, is sensitive to adduct concentration; the
residual ionic liquid in the adduct mixture contributes towards the initiation of the curing reaction. When a
monofunctional epoxy and the 1:1 adduct was subjected to a 2-week period of storage at room temperature and
sub-zero temperatures in the freezer, the profiles of the thermograms for the frozen samples do not change
considerably over the storage period and the formulation retains a light yellow colour (rather than the viscous,
dark red appearance of the formulation stored at room temperature).
The thermal decomposition of polyphenolic resins was studied by reactive molecular dynamics (RMD) simulation at elevated temperatures. Atomistic models of the polyphenolic resins to be used in the RMD were constructed using an automatic method which calls routines from the software package Materials Studio. In order to validate the models, simulated densities and heat capacities were compared with experimental values. The most suitable combination of force field and thermostat for this system was the Forcite force field with the Nosé?Hoover thermostat, which gave values of heat capacity closest to those of the experimental values. Simulated densities approached a final density of 1.05?1.08 g/cm3 which compared favorably with the experimental values of 1.16?1.21 g/cm3 for phenol-formaldehyde resins. The RMD calculations were run using LAMMPS software at temperatures of 1250 K and 3000 K using the ReaxFF force field and employing an in-house routine for removal of products of condensation. The species produced during RMD correlated with those found experimentally for polyphenolic systems and rearrangements to form cyclopropane moieties were observed. At the end of the RMD simulations a glassy carbon char resulted.
The reaction of phenyl glycidyl ether (PGE) with 1-ethyl-3-methylimidazolium acetate and 1-ethyl-3-methylimidazolium thiocyanate to initiate the polyetherification reaction was examined using thermal and spectral analysis techniques. The influence of the nucleophilicity of the anions on the deprotonation of the 1-ethyl-3-methylimidazolium cation determined the reaction pathway. The thermal degradation of the ionic liquid liberated the acetate ion and led, subsequently, to the deprotonation of the acidic proton in the imidazole ring. Thus, polymerisation of PGE occurred via a carbene intermediate. The more nucleophilic thiocyanate anion was not sufficiently basic to deprotonate the 1-ethyl-3-methylimidazolium cation, and thus proceeded through direct reaction with the PGE, unless the temperature was elevated and a competing carbene mechanism ensued.
Medicinal chemistry has in the past been dominated by learned insights from experienced organic chemists. However, with the advent of computer based methods, computer aided drug design has become prominent. We have compared here the ability of locally sourced expert medicinal chemists to purely automated methods and found that the automated method produces a better potential candidate drug than the expert input. The example chosen is based on inhibitors to Abl-kinase and the successful anti-leukaemic drug imatinib. The proposed molecule is a simple modification of nilotinib and has a docking energy of 4.2/kJ/mol better than the best intuitive molecule.
A new partially substituted calix pyrrole derivative obtained by the introduction of three thioamide functionalities in the N-rim has been synthesised and fully characterised by 1H,13C, HSQC, ROESY NMR and mass spectroscopy. Computer modelling suggested an alternate conformation which was confirmed through ROESY 1H NMR. The receptor interacts only with the silver cation as shown by 1H NMR. The strength of interaction is quantitatively assessed by titration calorimetry. N-rim modification eliminates the possibility of interaction with anions. Unlike calix pyrrole derivatives obtained by the introduction of functionalities through the meso-position, addition of Hg(NO3)2 leads to the degeneration of the receptor as demonstrated by 1H NMR, FTIR and XPS analyses. This is for the first time reported. Molecular simulation studies show significant strain in the mercury bound ligand in bonds, angles, torsions leading to the destruction of the receptor. Given the negative environmental impact produced by the availability of silver ions in aquatic organisms, the fundamental studies indicate that this receptor offers potential applications for monitoring silver (ion selective electrode) or indeed as a decontaminating material for removing silver ions from water.
This thesis examines two filter integrity tests: Forward Flow for hydrophilic membranes, FF, and Water Intrusion Testing for hydrophobic membranes, WIT.
Liquid filters are high area and diffusive flow through fully water-wetted pores masks bulk flow from the smallest defects during FF, so an alternative fluid was sought. Solutions were modelled and properties influential to diffusive flow identified using multi-linear regression. These were used for alternative fluid selection. Maltitol was identified as the fluid that would theoretically demonstrate most improvement. Experimental confirmation revealed a flow reduction of 23% at 10% concentration, compared with water.
WIT measures ?flow? through an un-wetted filter under pressure. If there is a defect present, this pressure will be sufficient to achieve breakthrough and the test will report a failure. Questions about WIT remained unanswered: what is the mechanism of ?flow?, and why is pressure the driver? The latter remains unanswered but conclusively demonstrated, and the former was proven as evaporative flow of water vapour. Salt/water was used, and conductivity reduced from 17.23 µS upstream to ~0 µS downstream, proving that the flow is water vapour evaporation.
Both tests have been improved by filter design.
FF requires every pore be fully wetted. An incompatibility between polypropylene and polyethersulphone means sometimes this cannot occur. The surface energy of the polypropylene is the property that provides the problem so it was altered by the incorporation of POSS, bringing the contact angle from 99.7° to 85.8°.
Altering air filter design to accommodate increased flow during WIT would be advantageous as customers relate higher flows to higher reliability. Space downstream was introduced by using a thicker support layer to increase flow successfully. Further improvement was demonstrated by modifying the core to a ?star? design, increasing flow by 3.3x for a commercially-available product and by 2.8x for an R&D prototype.
A recyclable mercury (II) selective dimer based on a calixpyrrole derivative has been synthesised
and characterised by Mass and FT- IR Spectrometry, Scanning Electron Microscopy (SEM) and
Energy Dispersive X-ray (EDX). Information regarding the ability of the dimer to interact with metal
cations was obtained from FTIR and SEM-EDX analyses. A striking feature of micrographs of the
loaded dimer is the change of morphology with the cation. Based on these results, optimal conditions
for removing cations from water were assessed under different experimental conditions. Results
obtained demonstrate that the removal process is fast. Capacity values and selectivity factors show that
the dimer is selective for Hg(II) in one and in multiple component metal solutions relative to other
cations. Single-ion transfer Gibbs energies from water to a solvent containing common functionalities to
those of the dimer were used to assess the counter-ion effect on the removal process. Agreement is
found between these data and energy calculations derived from Molecular Simulation studies. Studies
on polluted water in the presence of normal water components in addition to toxic metal cations are
reported. Further experimental work on wastewater from the mining industry is in progress.
Materials science is beginning to adopt computational simulation to eliminate laboratory trial and error campaigns?much like the pharmaceutical industry of 40 years ago. To further computational materials discovery, new methodology must be developed that enables rapid and accurate testing on accessible computational hardware. To this end, the authors utilise a novel methodology concept of intermediate molecules as a starting point, for which they propose the term ?symthon?a rather than conventional monomers. The use of symthons eliminates the initial monomer bonding phase, reducing the number of iterations required in the simulation, thereby reducing the runtime. A novel approach to molecular dynamics, with an NVT (Canonical) ensemble and variable unit cell geometry, was used to generate structures with differing physical and thermal properties. Additional script methods were designed and tested, which enabled a high degree of cure in all sampled structures. This simulation has been trialled on large-scale atomistic models of phenolic resins, based on a range of stoichiometric ratios of formaldehyde and phenol. Density and glass transition temperature values were produced, and found to be in good agreement with empirical data and other simulated values in the literature. The runtime of the simulation was a key consideration in script design; cured models can be produced in under 24 h on modest hardware. The use of symthons has been shown as a viable methodology to reduce simulation runtime whilst generating accurate models.
Mas Claret Eduard, Al Yahyaei Balqees, Chu Shuyu, Elliott Ruan M., Imperato Manuel, Lopez Arnaud, Meira Lisiane B., Howlin Brendan J., Whelligan Daniel K. (2020) An aza-nucleoside, fragment-like inhibitor of the DNA repair enzyme alkyladenine glycosylase (AAG), Bioorganic & Medicinal Chemistry 28 (11) 115507
The DNA repair enzyme AAG has been shown in mice to promote tissue necrosis in response to ischaemic reperfusion or treatment with alkylating agents. A chemical probe inhibitor is required for investigations of the biological mechanism causing this phenomenon and as a lead for drugs that are potentially protective against tissue damage from organ failure and transplantation, and alkylative chemotherapy. Herein, we describe the rationale behind the choice of arylmethylpyrrolidines as appropriate aza-nucleoside mimics for an inhibitor followed by their synthesis and the first use of a microplate-based assay for quantification of their inhibition of AAG. We finally report the discovery of an imidazol-4-ylmethylpyrrolidine as a fragment-sized, weak inhibitor of AAG.