Mark G. Williams

Testing the Vesicular Morphology to Destruction : Birth and Death of Diblock Copolymer Vesicles Prepared via Polymerization-Induced Self-Assembly

Small angle X-ray scattering (SAXS), electrospray ionization charge detection mass spectrometry (CD-MS), dynamic light scattering (DLS), and transmission electron microscopy (TEM) are used to characterize poly(glycerol monomethacrylate)55-poly(2-hydroxypropyl methacrylate)x (G55-Hx) vesicles prepared by polymerization-induced self-assembly (PISA) using a reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization formulation. A G55 chain transfer agent is utilized to prepare a series of G55-Hx diblock copolymers, where the mean degree of polymerization (DP) of the membrane-forming block (x) is varied from 200 to 2000. TEM confirms that vesicles with progressively thicker membranes are produced for x = 200–1000, while SAXS indicates a gradual reduction in mean aggregation number for higher x values, which is consistent with CD-MS studies. Both DLS and SAXS studies indicate minimal change in the overall vesicle diameter between x = 400 and 800. Fitting SAXS patterns to a vesicle model enables calculation of the membrane thickness, degree of hydration of the membrane, and the mean vesicle aggregation number. The membrane thickness increases at higher x values, hence the vesicle lumen must become smaller if the external vesicle dimensions remain constant. Geometric considerations indicate that this growth mechanism lowers the total vesicle interfacial area and hence reduces the free energy of the system. However, it also inevitably leads to gradual ingress of the encapsulated water molecules into the vesicle membrane, as confirmed by SAXS analysis. Ultimately, the highly plasticized membranes become insufficiently hydrophobic to stabilize the vesicle morphology when x exceeds 1000, thus this PISA growth mechanism ultimately leads to vesicle “death”.

Colloidosomes: synthesis, properties and applications.

Colloidosomes represent a rapidly expanding field with various applications in microencapsulation, including the triggered release of cargoes. With self-assembled shells comprising colloidal particles, they offer significant flexibility with respect to microcapsule functionality. This review explores the various types of particles and techniques that have been employed to prepare colloidosomes. The relative advantages and disadvantages of these routes are highlighted and their potential as microcapsules for both small molecule and macromolecular actives is evaluated.

Crystal and molecular structure of a seven-coordinate chloroindium(III) complex of 1,4,7-triazacyclononanetriacetic acid

Abstract The title macrocyclic ligand forms a seven-coordinate chloroindium complex which exists as a stable neutral hexacoordinate species in aqueous solution.

Cationic and reactive primary amine-stabilised nanoparticles via RAFT aqueous dispersion polymerisation

The synthesis of primary amine-functionalised diblock copolymer nanoparticles via polymerisation-induced self-assembly (PISA) using a RAFT aqueous dispersion polymerisation formulation is reported. The primary amine steric stabiliser is a macromolecular chain transfer agent (macro-CTA) based on 2-aminoethyl methacrylate AMA, which can be readily polymerised in its hydrochloride salt form with good control (Mw/Mn < 1.30) using RAFT aqueous solution polymerisation. Subsequent chain extension of this macro-CTA with 2-hydroxypropyl methacrylate (HPMA) leads to the formation of relatively monodisperse spherical nanoparticles (68 to 288 nm) at pH 6. However, worms or vesicles could not be obtained, because strong lateral repulsion between the highly cationic PAMA stabiliser chains impedes the formation of these higher order copolymer morphologies. Deprotonation of the primary amine stabiliser chains at or above pH 9 results in flocculation of these spherical nanoparticles as the PAMA block becomes uncharged. Diblock copolymer spheres, worms or vesicles can be synthesised that remain stable at pH 9 by supplementing the PAMA macro-CTA with a poly(glycerol monomethacrylate) (PGMA) macro-CTA, since this non-ionic block confers effective steric stabilisation in alkaline media. A series of diblock copolymer nanoparticles with the general formula ([1 − n]PGMAx + nPAMAy)–PHPMAz can be synthesised by optimising: (i) the mean degree of polymerisation (DP, or x) of the PGMA block, (ii) the PHPMA core-forming DP (or z); (iii) the mol fraction (n) of the PAMA stabiliser; and (iv) the copolymer concentration. These spheres, worms and vesicles are both cationic at low pH and colloidally stable at high pH. Furthermore, deprotonation of the protonated primary amine groups on the PAMA stabiliser chains at high pH renders these particles susceptible to epoxy-amine conjugation. This is demonstrated by the reaction between the primary amine groups on (0.8PGMA101 + 0.2PAMA96)–PHPMA1000 diblock copolymer spheres, and epoxide-functionalised diblock copolymer nanoparticles in aqueous solution at pH 8.

Bespoke cationic nano-objects via RAFT aqueous dispersion polymerisation

A range of cationic diblock copolymer nanoparticles are synthesised via polymerisation-induced self-assembly (PISA) using a RAFT aqueous dispersion polymerisation formulation. The cationic character of these nanoparticles can be systematically varied by utilising a binary mixture of two macro-CTAs, namely non-ionic poly(glycerol monomethacrylate) (PGMA) and cationic poly[2-(methacryloyloxy)ethyl]trimethylammonium chloride (PQDMA), with poly(2-hydroxypropyl methacrylate) (PHPMA) being selected as the hydrophobic core-forming block. Thus a series of cationic diblock copolymer nano-objects with the general formula ([1 − n] PGMAx + [n] PQDMAy) − PHPMAz were prepared at 20% w/w solids, where n is the mol fraction of the cationic block and x, y and z are the mean degrees of polymerisation of the non-ionic, cationic and hydrophobic blocks, respectively. These cationic diblock copolymer nanoparticles were analysed in terms of their chemical composition, particle size, morphology and cationic character using 1H NMR spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and aqueous electrophoresis, respectively. Systematic variation of the above PISA formulation enabled the formation of spheres, worms or vesicles that remain cationic over a wide pH range. However, increasing the cationic character favors the formation of kinetically-trapped spheres, since it leads to more effective steric stabilisation which prevents sphere–sphere fusion. Furthermore, cationic worms form a soft free-standing gel at 25 °C that undergoes reversible degelation on cooling, as indicated by variable temperature oscillatory rheology studies. Finally, the antimicrobial activity of this thermo-responsive cationic worm gel towards the well-known pathogen Staphylococcus aureus is examined via direct contact assays.

Inorganic/organic hybrid microcapsules: melamine formaldehyde-coated Laponite-based Pickering emulsions.

A facile synthesis route to novel inorganic/organic hybrid microcapsules is reported. Laponite nanoparticles are surface-modified via electrostatic adsorption of Magnafloc, an amine-based polyelectrolyte allowing the formation of stable oil-in-water Pickering emulsions. Hybrid microcapsules can be subsequently prepared by coating these Pickering emulsion precursors with dense melamine formaldehyde (MF) shells. Employing a water-soluble polymeric stabiliser, poly(acrylamide-co-sodium acrylate) leads to stable hybrid microcapsules that survive an alcohol challenge and the ultrahigh vacuum conditions required for SEM studies. Unfortunately, the presence of this copolymer also leads to secondary nucleation of excess MF latex particles in the aqueous continuous phase. However, since the Magnafloc is utilised at submonolayer coverage when coating the Laponite particles, the nascent cationic MF nanoparticles can deposit onto anionic surface sites on the Laponite, which removes the requirement for the poly(acrylamide-co-sodium acrylate) component. Following this electrostatic adsorption, the secondary amine groups on the Magnafloc chains can react with the MF, leading to highly robust cross-linked MF shells. The absence of the copolymer leads to minimal secondary nucleation of MF latex particles, ensuring more efficient deposition at the surface of the emulsion droplets. However, the MF shells appear to become more brittle, as SEM studies reveal cracking on addition of ethanol.

Metal-ion selectivity by macrocyclic ligands. Part 1. The interaction of NiII and CuII with pyridinyl-derived N3O2 macrocycles; the X-ray structures of a free macrocycle, its endomacrocyclic complexes of NiII and CuII and an exomacrocyclic nickel(II) complex

The interaction of CuII and NiII with two macrocycles L1 and L2, each containing an N3O2 donor set, has been investigated. Spectrophotometric studies in dimethyl sulphoxide reveal the formation of complexes with 1 : 1 and 1 : 2 metal : ligand ratios and conductometric studies in the same solvent indicated that all of the complexes were 1 : 2 electrolytes. Conductometric titration of the 1 : 1 copper(II) complexes with chloride in each case indicated the formation of a 1 : 1 electrolyte, presumably through co-ordination of a chloride ion to the central copper of each complex. Similar titration of the nickel(II) complexes gave evidence for the formation of dinuclear species; each of these was postulated to contain a bridging chloride anion. The stability constants of the complexes together with their enthalpies of co-ordination have been determined in 95% methanol. Extraction and related transport experiments were carried out and under the conditions employed CuII was favoured over NiII. The X-ray crystal structures of the free macrocycle L1, the 1 : 1 complexes [CuL1(H2O)][ClO4]2 and [NiL1(I)]I·MeOH, and the 1 : 2 complex [NiL12(NO3)]NO3·2MeOH have been determined. The metal in [CuL1(H2O)][ClO4]2 is six-co-ordinate and lies within the folded macrocyclic cavity. The donor set comprises the five macrocyclic donor atoms and a water molecule. Overall, the co-ordination sphere corresponds to a restricted tetragonal rhombic arrangement. The complex [NiL1(I)]I·MeOH also has all donors of the macrocycle co-ordinated with an iodide anion occupying the sixth site to yield a distorted-octahedral geometry. The structure of [NiL12(NO3)]NO3·2MeOH shows that the nickel is again six-co-ordinated, to the aliphatic nitrogen atoms from two macrocycles (each showing exo co-ordination) and a bidentate nitrate anion.

Metal-ion selectivity by macrocyclic ligands. Part 3. The interaction of MnII and CoII with pyridinyl-derived N3O2 macrocycles; X-ray structures of endomacrocyclic complexes of MnII and CoII

The interaction of MnII and CoII with the macrocycles L1 and L2, each containing an N3O2-donor set, has been investigated. Conductometric titration of the 1 : 1 MnII complexes with chloride indicated the formation of a 2 : 1 complex presumably through bridging of a chloride ion. The stability constants of the complexes have been determined in 95% methanol. The X-ray crystal structures of the 1 : 1 complexes [MnL1Br(EtOH)]ClO4 and [CoL1(NO3)]NO3, have been determined. The metal in [MnL1Br(EtOH)]ClO4 is seven-co-ordinate and lies within the macrocyclic cavity. The donor set comprises the five macrocyclic donor atoms, a bromide anion and an ethanol molecule. Overall, the co-ordination sphere corresponds to a distorted pentagonal-bipyramidal arrangement. The complex [CoL1(NO3)]NO3 also has all donors of the macrocycle co-ordinated together with a nitrate anion. The cobalt is seven-co-ordinated and the co-ordination polyhedron is intermediate between a capped trigonal prism and a pentagonal bipyramid.

Complexes of ligands providing endogenous bridges. Part 7. The concurrent formation of 1 + 1 and 2 + 2 oxa-azamacrocycles; the X-ray crystal structure of an exocyclic dinuclear copper(II) complex

A series of oxa-azamacrocycles derived from the non-template condensation of 1,3-diamino-2-propanol and acyclic dialdehydes followed by in situ reduction with tetrahydroborate has been prepared. Fast atom bombardment mass spectrometry (f.a.b.m.s.) showed the presence of 1 + 1 and 2 + 2 condensates and these were separated using medium pressure liquid chromatography. Metal complexes of the 1 + 1 macrocycles (HL) were prepared and characterised. Mononuclear complexes, M (HL)X2, were recovered for M = CoII, NII, ZnII, CdII, or HgII and X = Cl or Br and homo-dinuclear complexes, Cu2LCl2(OH)·nH2O, for CuCl2. The salts M(ClO4)2 and M(NO3)2(M = CoII, NiII, CuII, ZnII, or CdII) gave complexes [M(L)X] and f.a.b.m.s. provided evidence for oligomer formation. Mononuclear complexes were recovered from the reaction of one 2 + 2 macrocycle with M(ClO4)2(M = CoII, NiII, or ZnII) and CdCl2, whereas a homodinuclear complex was obtained for Cu(ClO4)2. The crystal structure of [Cu2(µ-C19H23N2O3)(µ-O2CPh)(OH2)Cl2]·2PhCH2OH reveals a dimeric structure in which the dinuclear units are linked by chloride bridges. The compound crystallises in monoclinic space group P21/c(C2h5 no. 14) with unit-cell dimensions a= 13.460(15), b= 14.608(16), c= 17.096(8)A, β= 96.227(9)°, and Z= 2; 3 678 independent reflections with I/σ(I) > 3.0 gave R= 0.0532.

Metal-ion selectivity by macrocyclic ligands. Part 2. The interaction of ZnII, CdII and HgII with pyridinyl-derived N3O2 macrocycles; X-Ray structures of one zinc and two cadmium endomacrocyclic complexes and of one zinc and one mercury exomacrocyclic complex

The interaction of ZnII, CdII and HgII with the macrocycles L1 and L2, each containing an N3O2-donor set, has been investigated. Conductometric titration of the 1:1 complexes of ZnII and CdII with chloride in each case indicated the sequential formation of a 1:1 electrolyte of the type [ML(Cl)]+ and a 2:1 electrolyte of the type [MLCl2] in each case. Proton NMR titration of the ligands with M(O2CMe)2 in CD3OD gave evidence for the formation of 1:1 and 1:2 (metal : ligand) species. The stability constants of the complexes have been determined in 95% methanol. The X-ray crystal structures of the 1:1 complexes [ZnL1I2]·H2O, [ZnL1(NO3)]NO3, [CdL1(NO3)(MeOH)]NO3, [CdL2-(ClO4)(MeCN)]ClO4 and [HgL1I2] have been determined. The metal atoms in [ZnL1I2]·H2O and [HgL1I2] are four-co-ordinated in a tetrahedral geometry and lie outside the macrocyclic cavity. The donor set in each molecule comprises the two secondary amine nitrogen atoms from the macrocycle and the two iodide anions. The complex [ZnL1(NO3)]NO3 has all donors of the macrocycle co-ordinated with one oxygen from a nitrate anion occupying the sixth site to yield an approximately trigonal-prismatic geometry. The structure of [CdL1(NO3)(MeOH)]NO3 shows that the metal is seven-co-ordinated in an approximately pentagonal-bipyramidal environment consisting of the full donor set of the macrocycle together with one oxygen each from a nitrate anion and a methanol of solvation. The structure of [CdL2(ClO4)(MeCN)]ClO4 shows that the metal has a similar co-ordination environment consisting of the full donor set of the macrocycle together with an oxygen from a perchlorate anion and a nitrogen from acetonitrile of solvation.