Noncovalent Interactions in the Catechol Dimer

Noncovalent interactions play a significant role in a wide variety of biological processes and bio-inspired species. It is, therefore, important to have at hand suitable computational methods for their investigation. In this paper, we report on the contribution of dispersion and hydrogen bonds in both stacked and T-shaped catechol dimers, with the aim of delineating the respective role of these classes of interactions in determining the most stable structure. By using second-order Møller–Plesset (MP2) calculations with a small basis set, specifically optimized for these species, we have explored a number of significant sections of the interaction potential energy surface and found the most stable structures for the dimer, in good agreement with the highly accurate, but computationally more expensive coupled cluster single and double excitation and the perturbative triples (CCSD(T))/CBS) method

Innovative Nanomaterial Approaches For Solar Energy Applications

The fundamental limitation of the conversion efficiency achievable with solar energy solutions (which includes photovoltaic and photothermal technology), requires the adaptation and integration of a series of innovative material strategies to continue the process of sustainably decarbonizing the global economy. Through the passive integration of additional nanoscale features which exploit and modify the solar spectrum through its interactions with luminescent molecules, metal nanoparticles, and/or thin-film optical coatings – the solar spectrum can be modulated and accordingly the collection efficiency of each respective technology enhanced. However, irrespective of the type of spectral conversion integrated into the technology (luminescent down-shifting, nanofluids, plasmonic luminescent down-shifting, or spectral beam splitting), a series of additional loss mechanisms are introduced as a result of the architectural modifications. Through a proposed series of innovative & iterative advancements in each one of these material strategies, the objective of alleviating the additional loss mechanisms through a suitable combination of the individual approaches could potentially be realised

Roles of hydrogen, halogen bonding and aromatic stacking in a series of Isophthalamides

Abstract: The synthesis and spectroscopic characterisation of six bis(5-X-pyridine-2-yl)isophthalamides (X = H, F, Br, Cl, I, NO2) are reported, together with five crystal structure analyses ( for X = H, F to I). The isophthalamides span a range of conformations as syn/anti (H-DIP; I-DIP), anti/anti- (F-DIP; Br-DIP) and with both present in ratio 2:1 in Cl-DIP. The essentially isostructural F-DIP and Br-DIP molecules (using strong amide . . . amide interactions) aggregate into 2D molecular sheets that align with either F/H or Br atoms at the sheet surfaces (interfaces), respectively. Sheets are linked by weak C-H· · · F contacts in F-DIP and by Br· · · Br halogen bonding interactions as a ‘wall of bromines’ at the Br atom rich interfaces in Br-DIP. Cl-DIP is an unusual crystal structure incorporating both syn/anti and anti/anti molecular conformations in the asymmetric unit (Z’ = 3). The I-DIP•1/2(H2O) hemihydrate structure has a water molecule residing on a twofold axis between two I-DIPs and has hydrogen and N· · · I (Nc = 0.88) halogen bonding. The hydrate is central to an unusual synthon and involved in six hydrogen bonding interactions/contacts. Contact enrichment analysis on the Hirshfeld surface demonstrates that F-DIP, Cl-DIP and Br-DIP have especially over-represented halogen···halogen interactions. With the F-DIP, Cl-DIP and Br-DIP molecules having an elongated skeleton, the formation of layers of halogen atoms in planes perpendicular to the long unit cell axis occurs in the crystal packings. All six DIPs were analysed by ab initio calculations and conformational analysis; comparisons are made between their minimized structures and the five crystal structures. In addition, physicochemical properties are compared and assessed

Modelling the self-assembly and structure of carbonaceous nanoparticles

The self-assembly and structure of carbonaceous particles are investigated using molecular modelling methods. This provides a deeper understanding of molecular interactions relevant to pollutant formation and growth in combustion processes and other carbon-based applications. The existing soot particle model, a cluster containing planar pericondensed polycyclic aromatic hydrocarbons (PAHs), is extended to include PAHs of varying sizes. The resulting nanostructures show that the classic core-shell morphology reported experimentally for mature soot particles is not energetically feasible if only considering physical interactions between PAHs. It is proposed that young soot particles present the inverse molecular size partitioning. A detailed survey of the surface properties of heterogeneous PAH clusters is conducted, identifying composition-, size- and temperature-dependent behaviours. A novel stochastic global optimisation method, the Sphere Encapsulated Monte Carlo method, is also developed to allow minimum energy structures of large aromatic systems to be determined at considerably less computational expense than existing methods. The properties of curved PAH molecules are then investigated, and it is hypothesised that their enhanced electronic interactions could play a role in soot particle nucleation. A new intermolecular potential, curPAHIP, is developed to allow the simulation of curved PAHs. Subsequent dynamic clustering studies show that there is a significant increase in particle formation for systems containing curved PAHs and cations, suggesting the importance of these interactions in combustion processes. Further work investigates the structure of clusters containing curved PAHs, and the corresponding influence of cluster size, molecule size and curvature, molecular ratio, and presence of ions. This work develops computational tools useful for examining large systems of aromatic molecules as well as those containing curved species. Detailed studies on nanoparticle nucleation, structure, and surface properties provide valuable information on self-assembly processes crucial to understanding the production and properties of carbonaceous nanoparticles.The Cambridge Trust and King's College, Cambridg

Extreme Conditions Crystallography of Polymorphic Co-crystals

This work has two principal sections. The first section is a study of the hydrogen bonding in a series of urea inclusion compounds, utilising neutron diffraction methods and a novel technique for growing neutron diffraction-suitable single crystals. The second section focusses on high pressure crystallography as a technique for exploring polymorphic landscapes, of a series of acid-base co-crystals, and the well-known active pharmaceutical ingredient 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY). Single crystal neutron structures at several temperatures have been determined for -phase urea inclusion compounds containing hexadecane, 1,6-dibromohexane and 2,7-octanedione guests. The neutron structure of the ‘partial channel’ co-crystal of urea and DMF is also reported. This includes an in-depth discussion and analysis of the structure and bonding of this urea series, in particular, how the guest compound affects the symmetry and hydrogen bonding of the host urea network. Additionally, the challenge of obtaining crystals suitable for neutron diffraction is addressed and a new heating/cooling device to aid crystallisation is presented. Pyridine and formic acid have been crystallised at differing ratios by both cryo-crystallisation and compression in a diamond anvil cell. Mixtures of the liquids in 1:1, 1:2 and 1:4 ratios all crystallise at high pressure, while only the 1:1 and 1:4 compositions were crystallised by in situ low temperature capillary crystallisation. The 1:2 structure crystallised by high pressure is a previously unknown co-crystal of pyridine - formic acid. For the 1:4 mixture, a new polymorph has been identified at a pressure of 14.2 kbar with a distinctly different structure and bonding pattern to that of the previously reported low temperature form. Five new co-crystals of 2,6-dimethylpyridine (DMP) with formic acid (FA) were crystallised by application of pressure in a diamond anvil cell and by in situ cryo-crystallisation. Mixtures in ratios 1:1, 1:2 and 1:3 of DMP: FA have been crystallised via both methods. Both the 1:2 and 1:3 co-crystals exhibit high pressure/low temperature polymorphism. ROY has been crystallised from acetone solution using a diamond anvil cell. The needle-like form obtained, named ONP shows similarities with the ORP, ON and Y forms, determined by Raman spectroscopy. The ONP crystals were recovered from the pressure cell by freezing with liquid nitrogen. Synchrotron X-ray data were collected on the sample, although no structure solution and refinement was possible. The unit cell of the ONP shows a crystallographic relationship to the ORP form

Hybrid Materials Consisting of Silver(I) Purine Complexes, Protonated Purines and Polyoxometalates

The present work is the first thorough exploration of the chemistry of the systems comprising purine bases and polyoxometalates (POMs). Different modes of interplay of these chemical species were employed in order to design and synthesize new compounds. The first type consisted majorly of materials in which polyoxoanions are interconnected by ditheobromine silver(I) complexes. The convenient aspect of the synthetic procedures is the possibility of obtaining the desired POM from basic materials by adjustment of the pH value of the reaction mixture. A ubiquitous structural trait of the target materials were one-dimensional coordination polymers consisting of polyoxoanions interconnected by [Ag(thb)2]+-complexes. Compounds based on iso- and heteropolyoxometalates of vanadium, chromium and molybdenum were obtained by this reaction procedure. Several similar compounds were obtained from benzonitrile as solvent. An intriguing unusual chemoselectivity regulated by guanine was observed under these reaction conditions. The solvent partly replaced the purine bases in the coordination sphere of silver(I) due to its strong σ-donor character. The protonated purine bases could also be employed for crystal engineering of organic-inorganic materials containing polyoxotungstates. The aromatic cations are arranged parallel to the faces of the POMs in all of the resulting crystal structures. The arrangement was named “nanoboxes” reflecting the size of the units. A compound containing a purine base covalently bound to a polyoxometalate Na2[(HGMP)2(Mo5O15)]•7H2O (GMP = guanosine monophosphate), crystallizes in space group P6522, which implies a helical structure in the solid state. The crystal structure consists of guanosine Strandberg anions interconnected by a network of coordinative, H-bonding and stacking interactions

Synthesis and Supramolecular Functional Assemblies of Ratiometric pH Probes

Tracking the pH with spatiotemporal resolution is a critical challenge for synthetic chemistry, chemical biology and beyond. Over the last decade different small probes and supramolecular systems have emerged for in celluloor in vivo pH tracking. However, pH reporting still presents critical limitations such as background reduction, sensor improved stability, cell targeting, endosomal escape, near and far infrared ratiometric pH tracking, adaptation to the new imaging techniques (i.e. super‐resolution), etc. These challenges will demand the combined efforts of synthetic and supramolecular chemistry working together to develop a next generation of smart materials that will resolve the current limitations. In this review we describe the recent advances in the synthesis of small fluorescent probes together with new supramolecular functional systems employed for pH tracking with emphasis in ratiometric probes. The combination of organic synthesis and stimuli‐responsive supramolecular functional materials will be essential to solve future challenges of pH tracking such as the improved signal to noise ratio, on target activation and microenvironment reportingThis work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [SAF2017-89890-R], the Xunta de Galicia (ED431C 2017/25, 2016-AD031 and Centro Singular de Investigación de Galicia accreditation 2016–2019, ED431G/09), the ISCIII (RD16/0008/003), and the European Union (European Regional Development Fund –ERDF). A.M. received a Marie Curie fellowship (GLYCONANOPEP-750248). J.M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Investigator Grant (DYNAP-677786) and a Young Investigator Grant from the Human Frontier Science Research Program (RGY0066/2017)S

Folding and aggregation studies in the acylphosphatase-like family

Folding and misfolding of proteins are considered two sides of the same coin. The delicate equilibrium existing between these two processes is crucial for any living organism and its alterations can lead to the onset of several tremendous diseases, such as Alzheimer's and Parkinson's disease. The attainment of a profound knowledge of folding/misfolding processes is a key step to understand how life works and for discovering new therapies to these diseases. In this work the author shows that proteins can display enzymatic activity even in the absence of a compact three-dimensional structure, with important implications for the study of protein enzymes. Furthermore, the author investigates the formation of protein aggregates similar to those observed in patients of amyloid-related diseases

MOLECULAR MODELING OF HIGH-PERFORMANCE THERMOSET POLYMER MATRIX COMPOSITES FOR AEROSPACE APPLICATIONS

The global efforts from major space agencies to transport humans to Mars will require a novel lightweight and ultra-high strength material for the spacecraft structure. Three decades of research with the carbon nanotubes (CNTs) have proved that the material can be an ideal candidate for the composite reinforcement if certain shortcomings are overcome. Also, the rapid development of the polymer resin industry has introduced a wide range of high-performance resins that show high compatibility with the graphitic surface of the CNTs. This research explores the computational design of these materials and evaluates their efficacy as the next generation of aerospace structural materials. Process-induced residual stresses are a commonly observed phenomenon in composite structures during the manufacturing process. These are generated because of resin shrinkage and relative thermal contraction between the resin and reinforcement during the curing process. Experimental or computational characterization of these stresses can be a challenge due to their complex nature. Predictive models of the curing process require detailed knowledge of the resin thermo-mechanical property evolution during the cure. Molecular Dynamics (MD) is implemented to predict the resin properties of EPON 828-Jeffamine D230 as a function of the crosslink density at room temperature. The molecular models are developed using the Reactive Interface Forcefield (IFF-R). The physical, mechanical, and thermal properties are validated experimentally and using the literature data. The predicted progression of resin properties indicates that each property evolves distinctively. The next generation of ultra-high strength composites for structural components of vehicles for crewed missions to deep space will incorporate flattened carbon nanotubes (flCNTs). With a wide range of high-performance polymers to choose from as the matrix component, efficient and accurate computational modeling can be used to efficiently down-select compatible resins, drive the design of these composites by predicting interface behavior, and provide critical physical insight into the flCNT/polymer interface. In this study, molecular dynamics simulation is used to predict the interaction energy, frictional sliding resistance, and mechanical binding of flCNT/polymer interfaces for a high-performance epoxy resin. The results, when compared to the sister studies, indicate that the BMI has stronger interfacial interaction and transverse tension binding with flCNT interfaces, while the benzoxazine demonstrates the strongest levels of interfacial friction resistance. Epoxy dwells in the “Goldilocks” zone with neither superior nor inferior properties. Comparison of these results indicate that BMI demonstrates the best overall compatibility with flCNTs for use in high-performance structural composites. One critical factor limiting the potential of carbon-based composites in aerospace applications is the poor load transferability between the reinforcement and the polymer matrix, which arises due to low interfacial shear strength at molecular scale. Molecular dynamics (MD) simulations have been employed in several studies that investigate the interface, such simulations are computationally expensive. To efficiently explore and optimize the interfacial design space with the goal of improving the mechanical performance, it is important to develop a machine learning (ML) approach that can be used to assist in the identification of optimal combinations of interface variables. In this study, a MD-ML workflow is proposed to predict optimal functionalization strategies for a bismaleimide (BMI) and three-layer graphene nanoplatelet (GNP) nanocomposite with maximized interfacial shear strength. In turn, these predictions of pull-out force will be used to identify optimal surface functionalizations that maximize the pull-out force. The details on the MD modeling and training data generation for the ML model are discussed in this work

Thermo-responsive Diels-Alder stabilized hydrogels for ocular drug delivery of a corticosteroid and an anti-VEGF fab fragment

In the present study, a novel in situ forming thermosensitive hydrogel system was investigated as a versatile drug delivery system for ocular therapy. For this purpose, two thermosensitive ABA triblock copolymers bearing either furan or maleimide moieties were synthesized, named respectively poly(NIPAM-co-HEA/Furan)-PEG 6K-P(NIPAM-co-HEA/Furan) (PNF) and poly(NIPAM-co-HEA/Maleimide)-PEG 6K-P(NIPAM-co-HEA/-Maleimide) (PNM). Hydrogels were obtained upon mixing aqueous PNF and PNM solutions followed by incubation at 37 °C. The hydrogel undergoes an immediate (<1 min) sol-gel transition at 37 °C. In situ hydrogel formation at 37 °C was also observed after intravitreal injection of the formulation into an ex vivo rabbit eye. The hydrogel network formation was due to physical self-assembly of the PNIPAM blocks and a catalyst-free furan-maleimide Diels-Alder (DA) chemical crosslinking in the hydrophobic domains of the polymer network. Rheological studies demonstrated sol-gel transition at 23 °C, and DA crosslinks were formed in time within 60 min by increasing the temperature from 4 to 37 °C. When incubated at 37 °C, these hydrogels were stable for at least one year in phosphate buffer of pH 7.4. However, the gels degraded at basic pH 10 and 11 after 13 and 3 days, respectively, due to hydrolysis of ester bonds in the crosslinks of the hydrogel network. The hydrogel was loaded with an anti-VEGF antibody fragment (FAB; 48.4 kDa) or with corticosteroid dexamethasone (dex) by dissolving (FAB) or dispersing (DEX) in the hydrogel precursor solution. The FAB fragment in unmodified form was quantitatively released over 13 days after an initial burst release of 46, 45 and 28 % of the loading for the 5, 10 and 20 wt% hydrogel, respectively, due to gel dehydration during formation. The low molecular weight drug dexamethasone was almost quantitively released in 35 days. The slower release of dexamethasone compared to the FAB fragement can likely be explained by the solubilization of this hydrophobic drug in the hydrophobic domains of the gel. The thermosensitive gels showed good cytocompatibility when brought in contact with macrophage-like mural cells (RAW 264.7) and human retinal pigment epithelium-derived (ARPE-19) cells. This study demonstrates that PNF-PNM thermogel may be a suitable formulation for sustained release of bioactive agents into the eye for treating posterior segment eye diseases