Publications
166 results found
Braddock D, Rowley B, Lickiss P, et al., 2023, On the use of triarylsilanols as catalysts for direct amidation of carboxylic acids, Journal of Organic Chemistry, Vol: 88, Pages: 9853-9869, ISSN: 0022-3263
Triarylsilanols are reported as the first silicon-centred molecular catalysts for direct amidation of carboxylic acids with amines as identified after a screen of silanols, silanediols, disiloxanediols and incompletely condensed silsesquioxanes as potential homogeneous catalysts. Subsequent synthesis and testing of various electronically differentiated triarylsilanols identify tris(p-haloaryl)silanols as more active than the parent triarylsilanol, where the bromide congener was found to be the most active. Catalyst decomposition can be observed by NMR methods, but RPKA methods reveal that product inhibition is operative, where tertiary amides are more inhibitory than secondary amides. Studies using an authentically synthesised triaryl silylester as a putative intermediate in the catalytic system enable a plausible mechanism to be proposed as supported by computations.
Braddock D, Davies J, Lickiss P, 2022, Methyltrimethoxysilane (MTM) as a reagent for direct amidation of carboxylic acids, Organic Letters, Vol: 24, Pages: 1175-1179, ISSN: 1523-7052
Methyltrimethoxysilane [MTM, CH3Si(OMe)3] has been demonstrated to be an effective, inexpensive, and safe reagent for the direct amidation of carboxylic acids with amines. Two simple workup procedures that provide the pure amide product without the need for further purification have been developed. The first employs an aqueous base-mediated annihilation of MTM. The second involves simple product crystallization from the reaction mixture providing a low process mass intensity direct amidation protocol.
Davies J, Braddock D, Lickiss P, 2021, Silicon compounds as stoichiometric coupling reagents for direct amidation, Organic and Biomolecular Chemistry, Vol: 19, Pages: 6746-6760, ISSN: 1477-0520
Despite being one of the most frequently carried out chemical reactions in industry, there is currently no amidation protocol that is regarded as safe, high yielding, environmentally friendly and inexpensive. The direct amidation of a carboxylic acid with an amine is viewed as an inherently good solution for developing such a protocol. Since the 1960s, there has been a gradual development in the use of silicon reagents for direct amidation. This review covers the methods published to April 2021 for silicon reagent mediated direct amidation of a carboxylic acid with an amine. This review also covers the use of polymeric SiO2 to promote direct amidation.
Podda E, Coles SJ, Horton PN, et al., 2021, First example of solid-state luminescent borasiloxane-based chiral helices assembled through N-B bonds, DALTON TRANSACTIONS, Vol: 50, Pages: 3782-3785, ISSN: 1477-9226
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- Citations: 8
Mohamed NA, Abou-Saleh H, Kameno Y, et al., 2021, Studies on metal-organic framework (MOF) nanomedicine preparations of sildenafil for the future treatment of pulmonary arterial hypertension, Scientific Reports, Vol: 11, Pages: 1-8, ISSN: 2045-2322
Pulmonary arterial hypertension (PAH) is an incurable disease, although symptoms are treated with a range of dilator drugs. Despite their clinical benefits, these drugs are limited by systemic side-effects. It is, therefore, increasingly recognised that using controlled drug-release nanoformulation, with future modifications for targeted drug delivery, may overcome these limitations. This study presents the first evaluation of a promising nanoformulation (highly porous iron-based metal–organic framework (MOF); nanoMIL-89) as a carrier for the PAH-drug sildenafil, which we have previously shown to be relatively non-toxic in vitro and well-tolerated in vivo. In this study, nanoMIL-89 was prepared and charged with a payload of sildenafil (generating Sil@nanoMIL-89). Sildenafil release was measured by Enzyme-Linked Immunosorbent Assay (ELISA), and its effect on cell viability and dilator function in mouse aorta were assessed. Results showed that Sil@nanoMIL-89 released sildenafil over 6 h, followed by a more sustained release over 72 h. Sil@nanoMIL-89 showed no significant toxicity in human blood outgrowth endothelial cells for concentrations up to100µg/ml; however, it reduced the viability of the human pulmonary artery smooth muscle cells (HPASMCs) at concentrations > 3 µg/ml without inducing cellular cytotoxicity. Finally, Sil@nanoMIL-89 induced vasodilation of mouse aorta after a lag phase of 2–4 h. To our knowledge, this study represents the first demonstration of a novel nanoformulation displaying delayed drug release corresponding to vasodilator activity. Further pharmacological assessment of our nanoformulation, including in PAH models, is required and constitutes the subject of ongoing investigations.
Delmas LC, White AJP, Pugh D, et al., 2020, Stable metal-organic frameworks with low water affinity built from methyl-siloxane linkers, CHEMICAL COMMUNICATIONS, Vol: 56, Pages: 7905-7908, ISSN: 1359-7345
Al-Ansari DE, Mohamed NA, Marei I, et al., 2020, Internalization of Metal-Organic Framework Nanoparticles in Human Vascular Cells: Implications for Cardiovascular Disease Therapy, NANOMATERIALS, Vol: 10
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- Citations: 8
Mohamed NA, Davies RP, Lickiss PD, et al., 2019, Mil-89 nanoformulation as a platform to improve pulmonary arterial hypertension treatment, British-Pharmacology-Society Meeting (Pharmacology), Publisher: WILEY, Pages: 3075-3075, ISSN: 0007-1188
Pugh D, Ashworth E, Robertson K, et al., 2019, Metal-organic frameworks constructed from group 1 metals (Li, Na) and silicon-centered linkers, Crystal Growth and Design, Vol: 19, Pages: 487-497, ISSN: 1528-7483
A series of “light metal” metal–organic frameworks containing secondary building units (SBUs) based on Li+ and Na+ cations have been prepared using the silicon-centered linkers MexSi(p-C6H4CO2H)4-x (x = 2, 1, 0). The unipositive charge, small size, and oxophilic nature of the metal cations give rise to some unusual and unique SBUs, including a three-dimensional nodal structure built from sodium and oxygen ions when using the triacid linker (x = 1). The same linker with Li+ cations generated a chiral, helical SBU, formed from achiral starting materials. One-dimensional rod SBUs are observed for the diacid (x = 2) and tetra-acid (x = 0) linkers with both Li+ and Na+ cations, where the larger size of Na+ compared to Li+ leads to subtle differences in the constitution of the metal nodes.
Davies RP, Delmas L, Horton P, et al., 2019, Studies on the structural diversity of MOFs containing octahedral siloxane-backboned connectors, Polyhedron, Vol: 157, Pages: 25-32, ISSN: 0277-5387
Four metal–organic frameworks containing hexatopic connectors have been prepared and structurally characterised: [Cd3(L)(DMA)2(H2O)2] (IMP-28), [Ce2(L)(DMF)2(H2O)2] (IMP-29), [Y2(L)(DMF)2(H2O)2] (IMP-30), and [Zn2(L-H2)(4,4′-bipy)2] (IMP-31). All the MOFs have been constructed using the hybrid inorganic–organic siloxane linker hexakis(4-carboxyphenyl)disiloxane (L-H6). In each case, discrete metal-based nodes are cross-linked by the octahedrally disposed connector to afford 3D polymeric structures. The underlying nets in these MOFs have been evaluated through deconstruction of their crystal structures and subsequent topological analysis. Examples of MOFs built from hexatopic linkers, and especially those with octahedral predispositions such as in L, remain scarce and the topologies ascribed to some of these MOFs are unique.
Delmas L, White A, Pugh D, et al., 2018, Trisiloxane-centred metal-organic frameworks and hydrogen bonded assemblies, CrystEngComm, Vol: 20, Pages: 4541-4545, ISSN: 1466-8033
A hexacarboxylic acid with a trisiloxane backbone (L-H6) has been prepared and applied in MOF construction. L-H6 itself crystallizes as an unusual 2D hydrogen-bonded network. Reaction of L-H6 with Mn(II) gave IMP-20 and with Zn(II) gave IMP-21: both are 3D MOFs incorporating Si–O–Si–O–Si linkages.
Braddock DC, Lickiss P, Rowley B, et al., 2018, Tetramethyl orthosilicate (TMOS) as a reagent for direct amidation of carboxylic acids, Organic Letters, Vol: 20, Pages: 950-953, ISSN: 1523-7052
Tetramethyl orthosilicate (TMOS) is shown to be an effective reagent for direct amidation of aliphatic and aromatic carboxylic acids with amines and anilines. The amide products are obtained in good to quantitative yields in pure form directly after workup without the need for any further purification. A silyl ester as the putative activated intermediate is observed by NMR methods. Amidations on a 1 mol scale are demonstrated with a favorable process mass intensity.
Davies RP, Delmas L, Horton PN, et al., 2017, Siloxane-based linkers in the construction of hydrogen bonded assemblies and porous 3D MOFs, Chemical Communications, Vol: 53, Pages: 12524-12527, ISSN: 1359-7345
A siloxane-based hexacarboxylic acid (L1-H6) has been prepared and applied in MOF construction. L1-H6 itself crystallizes as an unusual interpenetrated 3D hydrogen-bonded framework. Reaction of L1-H6 with Zn(II) gave IMP-18 – a 3D MOF incorporating Si–O–Si functionality. Cleavage of L1-H6 gives a silanol-based triacid which is shown to give a coordination polymer (IMP-19) with Zn(II).
Mohamed NA, Davies RP, Lickiss PD, et al., 2017, Chemical and biological assessment of metal organic frameworks (MOFs) in pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial hypertension therapy, Pulmonary Circulation, Vol: 7, Pages: 1-11, ISSN: 2045-8940
Pulmonary arterial hypertension (PAH) is a progressive and debilitating condition. Despite promoting vasodilation, current drugs have a therapeutic window within which they are limited by systemic side effects. Nanomedicine uses nanoparticles to improve drug delivery and/or reduce side effects. We hypothesize that this approach could be used to deliver PAH drugs avoiding the systemic circulation. Here we report the use of iron metal organic framework (MOF) MIL-89 and PEGylated MIL-89 (MIL-89 PEG) as suitable carriers for PAH drugs. We assessed their effects on viability and inflammatory responses in a wide range of lung cells including endothelial cells grown from blood of donors with/without PAH. Both MOFs conformed to the predicted structures with MIL-89 PEG being more stable at room temperature. At concentrations up to 10 or 30 µg/mL, toxicity was only seen in pulmonary artery smooth muscle cells where both MOFs reduced cell viability and CXCL8 release. In endothelial cells from both control donors and PAH patients, both preparations inhibited the release of CXCL8 and endothelin-1 and in macrophages inhibited inducible nitric oxide synthase activity. Finally, MIL-89 was well-tolerated and accumulated in the rat lungs when given in vivo. Thus, the prototypes MIL-89 and MIL-89 PEG with core capacity suitable to accommodate PAH drugs are relatively non-toxic and may have the added advantage of being anti-inflammatory and reducing the release of endothelin-1. These data are consistent with the idea that these materials may not only be useful as drug carriers in PAH but also offer some therapeutic benefit in their own right.
Tome LC, Gouveia ASL, Ab Ranii MA, et al., 2017, Study on Gas Permeation and CO2 Separation through Ionic Liquid Based Membranes with Siloxane-Functionalized Cations, Industrial & Engineering Chemistry Research, Vol: 56, Pages: 2229-2239, ISSN: 0888-5885
This work explores ionic liquid-based membranes with siloxane functionalized cations using two different approaches: supported ionic liquid membranes (SILMs) and poly(ionic liquid)–ionic liquid (PIL–IL) composite membranes. Their CO2, CH4, and N2 permeation properties were measured at T = 293 K with a trans-membrane pressure differential of 100 kPa. The thermophysical properties of the synthesized siloxane-functionalized ILs, namely viscosity and density (data in the Supporting Information), were also determined. Contrary to what was expected, the gas permeation results show that the SILMs containing siloxane-functionalized cations have CO2 permeabilities that are lower than those of their analogues without the siloxane functionality. The addition of siloxane-based ILs into PILs increases both CO2 permeability and CO2/N2 permselectivity, although it does not significantly change the CO2/CH4 permselectivity. The prepared membranes present very diverse CO2 permeabilities, between 57 and 568 Barrer, while they show permselectivities varying from 16.8 to 36.8 for CO2/N2 and from 9.8 to 11.5 for CO2/CH4. As observed for other ILs, superior CO2 separation performances were obtained when the IL containing [C(CN)3]− is used compared to that having the [NTf2]− anion.
Mohamed NA, Ahmetaj-Shala B, Duluc L, et al., 2016, A New NO-Releasing Nanoformulation for the Treatment of Pulmonary Arterial Hypertension., Journal of Cardiovascular Translational Research, Vol: 9, Pages: 162-164, ISSN: 1937-5395
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease which continues to carry an unacceptably high mortality and morbidity. The nitric oxide (NO) pathway has been implicated in the pathophysiology and progression of the disease. Its extremely short half-life and systemic effects have hampered the clinical use of NO in PAH. In an attempt to circumvent these major limitations, we have developed a new NO-nanomedicine formulation. The formulation was based on hydrogel-like polymeric composite NO-releasing nanoparticles (NO-RP). The kinetics of NO release from the NO-RP showed a peak at about 120 min followed by a sustained release for over 8 h. The NO-RP did not affect the viability or inflammation responses of endothelial cells. The NO-RP produced concentration-dependent relaxations of pulmonary arteries in mice with PAH induced by hypoxia. In conclusion, NO-RP drugs could considerably enhance the therapeutic potential of NO therapy for PAH.
Mohamed NA, Davies R, Lickiss PD, et al., 2016, In Vivo Assessment of Metal Organic Framework (MOFs) for the Future use as Delivery Agents for Drugs to Treat PAH
Pulmonary arterial hypertension (PAH) is a progressive, debilitating and fatal condition with no cure. However small molecule drugs, including sildenafil, selexipag and bosentan, have been developed and are used to treat PAH but do not offer a cure and life expectancy, even on medication, is only between 2-5 years after diagnosis. All PAH drugs are ubiquitous dilators and their therapeutic dose is severely limited by their systemic side-effects [1]. We are working on the hypothesis that current PAH-drugs could be used more effectively at higher local (to the lung) concentrations if delivered selectively using a nanomedicine approach. We suggest that if toxicological limitations of nanomedicines can be overcome their use in PAH to delivery current drugs to the lung could turn this fatal disease to a chronic drug-managedcondition. One nanoparticle that we are interested in is from the Materials of Institute Lavoisier (MIL), the so called MIL-89. MIL-89 is an iron based metal organic framework (MOF). MIL-89 is a good candidate for delivery of drugs because (i) it can be tailored to accommodate different drugs including those with the molecular weights of current PAH-medications (MW; 300-500) [2], (ii) it is biocompatible and biodegradable [3]; (iii) it has a large internal surface area and high drug loading capacity; (iv) it is thermally and mechanically stable; and (v) it promises a long drug release-period with the ability to incorporate different functional groups [2, 4-5]. We have previously shown that MIL-89 at concentrations up to 10µg/ml is non-toxic to human lung cells including those from patients with PAH. In the current study we have investigated the effects of MIL-89 in rats in vivo for markers of toxicity. MIL-89 at 50mg/kg was administered (i.p.) for two weeks at days 0, 1, 3, 7, 10 and 14. At each time point rats were weighed, killed, plasma and tissues collected. MIL-89 had no effect on body weight, lung oedema or on plasma markers of organ failur
Wann DA, Young S, Baetz K, et al., 2015, Structures of Tetrasilylmethane Derivatives C(SiXMe<sub>2</sub>)<sub>4</sub> (X = H, F, Cl, Br) in the Gas Phase and their Dynamic Structures in Solution, ZEITSCHRIFT FUR NATURFORSCHUNG SECTION B-A JOURNAL OF CHEMICAL SCIENCES, Vol: 69, Pages: 1321-1332, ISSN: 0932-0776
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- Citations: 1
Wann DA, Robinson MS, Baetz K, et al., 2015, Structures of Tetrasilylmethane Derivatives (XMe<sub>2</sub>Si)<sub>2</sub>C(SiMe<sub>3</sub>)<sub>2</sub> (X = H, Cl, Br) in the Gas Phase, and their Dynamic Structures in Solution, JOURNAL OF PHYSICAL CHEMISTRY A, Vol: 119, Pages: 786-795, ISSN: 1089-5639
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- Citations: 1
Wann DA, Reilly AM, Rataboul F, et al., 2014, The Gas-phase Structure of the Hexasilsesquioxane Si<sub>6</sub>O<sub>9</sub>(OSiMe<sub>3</sub>)<sub>6</sub>, ZEITSCHRIFT FUR NATURFORSCHUNG SECTION B-A JOURNAL OF CHEMICAL SCIENCES, Vol: 64, Pages: 1269-1275, ISSN: 0932-0776
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- Citations: 6
Timokhin I, White AJP, Lickiss PD, et al., 2014, Microporous metal-organic frameworks built from rigid tetrahedral tetrakis(4-tetrazolylphenyl)silane connectors, CRYSTENGCOMM, Vol: 16, Pages: 8094-8097, ISSN: 1466-8033
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- Citations: 14
Ab Rani MA, Borduas N, Colquhoun V, et al., 2013, The potential of methylsiloxanes as solvents for synthetic chemistry applications, Green Chemistry, Vol: 16, Pages: 1282-1296, ISSN: 1744-1560
The potential use of volatile methylsiloxanes (VMSs) as solvents for chemicals synthesis has been explored. Assessment of the environmental impact of these VMS solvents is made and found to be significantly lower than those of the non-polar organic solvents that they have the potential to replace. The polarities of the VMSs, as expressed by empirical polarity measurements, and miscibilities with other liquids are found to be similar to those of alkane solvents. Finally, some uses of VMSs as solvents for both organic and inorganic transformations are described. The VMSs provide environmentally more sustainable (greener) alternatives to the nonpolar solvents that they have the potential to replace.
Timokhin I, Torres JB, White AJP, et al., 2013, Organosilicon linkers in metal organic frameworks: the tetrahedral tetrakis(4-tetrazolylphenyl)silane ligand, DALTON TRANSACTIONS, Vol: 42, Pages: 13806-13808, ISSN: 1477-9226
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- Citations: 14
Bulut S, Ab Rani MA, Welton T, et al., 2012, Preparation of [Al(hfip)4]--Based Ionic Liquids with Siloxane-Functionalized Cations and Their Physical Properties in Comparison with Their [Tf2N]- Analogues, CHEMPHYSCHEM, Vol: 13, Pages: 1802-1805, ISSN: 1439-4235
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- Citations: 17
Davies RP, Lickiss PD, Robertson K, et al., 2012, An organosilicon hexacarboxylic acid and its use in the construction of a novel metal organic framework isoreticular to MOF-5, CRYSTENGCOMM, Vol: 14, Pages: 758-760, ISSN: 1466-8033
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- Citations: 23
Davies RP, Lickiss PD, Robertson K, et al., 2012, An Organosilicon hexacarboxylic acid and its use in the construction of a novel metal organic framework isoreticular to MOF-5, CrystEngComm, Vol: 14, Pages: 758-760
A novel hexacarboxylate organo-silicon molecule has been synthesised and used in the construction of a new MOF of pcu topology and isoreticular to MOF-5.
Wann DA, Dickson CN, Lickiss PD, et al., 2011, The Gas-Phase Equilibrium Structures of Si<sub>8</sub>O<sub>12</sub>(OSiMe<sub>3</sub>)<sub>8</sub> and Si<sub>8</sub>O<sub>12</sub>(CHCH<sub>2</sub>)<sub>8</sub>, INORGANIC CHEMISTRY, Vol: 50, Pages: 2988-2994, ISSN: 0020-1669
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- Citations: 13
Davies RP, Lickiss PD, Robertson K, 2011, Coordination polymers containing novel silicon-based connectors, 241st National Meeting and Exposition of the American-Chemical-Society (ACS), Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727
Davies RP, Lickiss PD, Robertson K, et al., 2011, Mg<SUP>II</SUP>, Ca<SUP>II</SUP>, and Co<SUP>II</SUP> Metal-Organic Framework Materials with [Si(<i>p</i>-C<sub>6</sub>H<sub>4</sub>CO<sub>2</sub>)<sub>3</sub>(<i>p</i>-C<sub>6</sub>H<sub>4</sub>CO<sub>2</sub>H)]<SUP>3-</SUP> Struts, AUSTRALIAN JOURNAL OF CHEMISTRY, Vol: 64, Pages: 1237-1244, ISSN: 0004-9425
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- Citations: 20
Davies RP, Less R, Lickiss PD, et al., 2010, Structural Diversity in Metal-Organic Frameworks Built from Rigid Tetrahedral [Si(<i>p</i>-C<sub>6</sub>H<sub>4</sub>CO<sub>2</sub>)<sub>4</sub>]<SUP>4-</SUP> Struts, CRYSTAL GROWTH & DESIGN, Vol: 10, Pages: 4571-4581, ISSN: 1528-7483
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- Citations: 69
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