Nanoparticle-Cell Interactions: Surface Chemistry Effects on the Cellular Uptake of Biocompatible Block Copolymer Assemblies.

The development of nanovehicles for intracellular drug delivery is strongly bound to the understating and control of nanoparticles cellular uptake process, which in turn is governed by surface chemistry. In this study, we explored the synthesis, characterization, and cellular uptake of block copolymer assemblies consisting of a pH-responsive poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) core stabilized by three different biocompatible hydrophilic shells (a zwitterionic type poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer, a highly hydrated poly(ethylene oxide) (PEO) layer with stealth effect, and an also proven nontoxic and nonimmunogenic poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) layer). All particles had a spherical core-shell structure. The largest particles with the thickest hydrophilic stabilizing shell obtained from PMPC40-b-PDPA70 were internalized to a higher level than those smaller in size and stabilized by PEO or PHPMA and produced from PEO122-b-PDPA43 or PHPMA64-b-PDPA72, respectively. Such a behavior was confirmed among different cell lines, with assemblies being internalized to a higher degree in cancer (HeLa) as compared to healthy (Telo-RF) cells. This fact was mainly attributed to the stronger binding of PMPC to cell membranes. Therefore, cellular uptake of nanoparticles at the sub-100 nm size range may be chiefly governed by the chemical nature of the stabilizing layer rather than particles size and/or shell thickness.

Gene Transfection Mediated by Catiomers Requires Free Highly Charged Polymer Chains To Overcome Intracellular Barriers.

The prospective use of the block copolymers poly(ethylene oxide)113-b-poly[2-(diethylamino)ethyl methacrylate]50 (PEO113-b-PDEA50) and poly[oligo(ethylene glycol)methyl ether methacrylate]70-b-poly[oligo(ethylene glycol)methyl ether methacrylate10-co-2-(diethylamino)ethyl methacrylate47-co-2-(diisopropylamino)ethyl methacrylate47] (POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47)) as nonviral gene vectors was evaluated. The polymers are able to properly condense DNA into nanosized particles (RH ≈ 75 nm), which are marginally cytotoxic and can be uptaken by cells. However, the green fluorescent protein (GFP) expression assays evidenced that DNA delivery is essentially negligible meaning that intracellular trafficking hampers efficient gene release. Subsequently, we demonstrate that cellular uptake and particularly the quantity of GFP-positive cells are substantially enhanced when the block copolymer polyplexes are produced and further supplemented by BPEI chains (branched polyethylenimine). The dynamic light scattering/electrophoretic light scattering/isothermal titration calorimetry data suggest that such a strategy allows the adsorption of BPEI onto the surface of the polyplexes, and this phenomenon is responsible for increasing the size and surface charge of the assemblies. Nevertheless, most of the BPEI chains remain freely diffusing in the systems. The biological assays confirmed that cellular uptake is enhanced in the presence of BPEI and principally, the free highly charged polymer chains play the central role in intracellular trafficking and gene transfection. These investigations pointed out that the transfection efficiency versus cytotoxicity issue can be balanced by a mixture of BPEI and less cytotoxic agents such as for instance the proposed block copolymers.

Efficient Condensation of DNA into Environmentally Responsive Polyplexes Produced from Block Catiomers Carrying Amine or Diamine Groups.

The intracellular delivery of nucleic acids requires a vector system as they cannot diffuse across lipid membranes. Although polymeric transfecting agents have been extensively investigated, none of the proposed gene delivery vehicles fulfill all of the requirements needed for an effective therapy, namely, the ability to bind and compact DNA into polyplexes, stability in the serum environment, endosome-disrupting capacity, efficient intracellular DNA release, and low toxicity. The challenges are mainly attributed to conflicting properties such as stability vs efficient DNA release and toxicity vs efficient endosome-disrupting capacity. Accordingly, investigations aimed at safe and efficient therapies are still essential to achieving gene therapy clinical success. Taking into account the mentioned issues, herein we have evaluated the DNA condensation ability of poly(ethylene oxide)113-b-poly[2-(diisopropylamino)ethyl methacrylate]50 (PEO113-b-PDPA50), poly(ethylene oxide)113-b-poly[2-(diethylamino)ethyl methacrylate]50 (PEO113-b-PDEA50), poly[oligo(ethylene glycol)methyl ether methacrylate]70-b-poly[oligo(ethylene glycol)methyl ether methacrylate10-co-2-(diethylamino)ethyl methacrylate47-co-2-(diisopropylamino)ethyl methacrylate47] (POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47), and poly[oligo(ethylene glycol)methyl ether methacrylate]70-b-poly{oligo(ethylene glycol)methyl ether methacrylate10-co-2-methylacrylic acid 2-[(2-(dimethylamino)ethyl)methylamino]ethyl ester44} (POEGMA70-b-P(OEGMA10-co-DAMA44). Block copolymers PEO113-b-PDEA50 and POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47) were evidenced to properly condense DNA into particles with a desirable size for cellular uptake via endocytic pathways (R(H) ≈ 65-85 nm). The structure of the polyplexes was characterized in detail by scattering techniques and atomic force microscopy. The isothermal titration calorimetric data revealed that the polymer/DNA binding is endothermic; therefore, the process in entropically driven. The combination of results supports that POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47) condenses DNA more efficiently and with higher thermodynamic outputs than does PEO113-b-PDEA50. Finally, circular dichroism spectroscopy indicated that the conformation of DNA remained the same after complexation and that the polyplexes are very stable in the serum environment.

Polymer-coated palladium nanoparticle catalysts for Suzuki coupling reactions.

A set of seven different palladium nanoparticle (PdNP) systems stabilized by small amounts (1.0mg/mL) of structurally related macromolecular capping agents were comparatively tested as catalyst in p-nitrophenol (Nip) reduction and Suzuki cross-coupling reactions. The observed rate constants (kobs) for Nip reduction were in the range of 0.052-3.120×10(-2)s(-1), and the variation reflected the effects of polymer chain conformation, ionic strength and palladium-polymer complex coordination. Macromolecules featuring pendant pyridyl moieties or inverse temperature-dependent solubility were found to be unsuitable capping agents for PdNPs catalysts, despite being active. The catalytic activity in Suzuki cross-coupling reactions followed the same behavior; the most active particles in the Nip reaction also mediated the cross-coupling reaction providing the expected products in quantitative yields under relatively mild conditions after only 4h at 50°C. Experiments involving the successive addition of reactants and catalyst recovery/re-use indicated that the recycling potential was comparable to those of the standards used in this field.

Direct synthesis of coated gold nanoparticles mediated by polymers with amino groups.

The single-step/single-phase synthesis of hybrid organic-inorganic core-shell gold nanoparticles (AuNPs), facilitated by amino-functionalized amphiphilic block copolymers that simultaneously play the roles of reductant and stabilizer, was investigated in this study. Experiments were devised with emphasis on the pH-responsive poly(ethylene oxide)-b-poly(2,3-dihydroxypropyl methacrylate)-b-poly[2-(diisopropylamino)ethyl methacrylate] triblock copolymer, which allows direct chemical cross-linking of the micellar structures to be performed. The polymer structure-reactivity relationship associated with the AuNP formation was established using a set of six structurally related macromolecules. AuNP formation was dependent on the aqueous dissociation equilibrium involving tertiary amino groups, the Au(III) speciation, and electrochemical redox potentials. The effects of these parameters on the synthesis of AuNPs change as the solution pH is increased from pH 3.3 (molecularly dissolved polymer chains; no AuNP formation) to 6.8 or higher (polymer chains self-assembled into spherical micelles; stable gold sols are produced), and Au(III) reduction potentials shift toward the cathodic region while the oxidation potential of deprotonated amino groups decreases. Sigmoidal nanoparticle growth kinetics was observed in all cases after a characteristic induction period. Stable, well-defined, uniform polymer-coated gold colloids with localized surface plasmon resonance centered at 53 0nm can be conveniently produced in one-pot, two-reactant, no work-up reactions when the stoichiometry is [N]/[Au]=3.5-25.0.

Film/contact loading method improves the encapsulated amount of triazene anticancer compounds in polymeric micelles.

The development of organic solvent-free methods for the encapsulation of hydrophobic molecules is necessary for advances in micelle-mediated drug delivery. In this study we investigated the film/contact approach in which the use of organic solvents is limited to the preparation of a dry film before encapsulation. Unloaded micelles of five structurally related block copolymers were placed in contact with thin homogeneous films of two hydrophobic triazene anticancer compounds (1-(4-amidophenyl)-3-(4-acetylphenyl)triazene (1) and corresponding triazenido complex with triphenylphosphanegold(I) fragment (2)). The micelle surface becomes saturated with the drug, which eventually penetrates as a front into the core. Because the drug interacts with both the shell and the core microenvironments of micelle during the process, the maximum loading capacities were very sensitive to block copolymer micelle composition, ranging from 2.2 to 20.4% (wt./wt. of polymer). We conclude that micelles with poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) cores are the best option for the encapsulation of triazene compounds because i) they are prepared in absence of organic phase; ii) the drug concentration in the particles is high enough for a therapeutic effect and iii) the responsiveness properties of PDPA is appropriate for practical applications in pH-triggered drug release systems.

Light scattering evidence of selective protein fouling on biocompatible block copolymer micelles.

Selective protein fouling on block copolymer micelles with well-known potential for tumour-targeting drug delivery was evidenced by using dynamic light scattering measurements. The stability and interaction of block copolymer micelles with model proteins (BSA, IgG, lysozyme and CytC) is reported for systems featuring a hydrophobic (poly[2-(diisopropylamino)-ethyl methacrylate]) (PDPA) core and hydrophilic coronas comprising poly(ethylene oxide)/poly(glycerol monomethacrylate) (PEO-b-PG2MA) or poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC). The results revealed that protein size and hydrophilic chain density play important roles in the observed interactions. The PEO(113)-b-PG2MA(30)-b-PDPA(50) nanoparticles are stable and protein adsorption is prevented at all investigated protein environments. The successful protein-repellent characteristic of these nanoparticles is attributed to a high hydrophilic surface chain density (>0.1 chains per nm(2)) and to the length of the hydrophilic chains. On the other hand, although PMPC also has protein-repellent characteristics, the low surface chain density of the hydrophilic shell is supposed to enable interactions with small proteins. The PMPC(40)-b-PDPA(70) micelles are stable in BSA and IgG environments due to weak repulsion forces between PMPC and the proteins, to the hydration layer, and particularly to a size-effect where the large BSA (R(H) = 4.2 nm) and IgG (R(H) = 7.0 nm) do not easily diffuse within the PMPC shell. Conversely, a clear interaction was observed with the 2.1 nm radius lysozyme. The lysozyme protein can diffuse within the PMPC micellar shell towards the PDPA hydrophobic core in a process favored by its smaller size and the low hydrophilic PMPC surface chain density (∼0.049 chains per nm(2)) as compared to PEO-b-PG2MA (∼0.110 chains per nm(2)). The same behavior was not evidenced with the 2.3 nm radius positively charged CytC, probably due to its higher surface hydrophilicity and the consequent chemical incompatibility with PDPA.

Fluorescent vesicles consisting of galactose-based amphiphilic copolymers with a π-conjugated sequence self-assembled in water.

Fluorescent vesicles considered as a mimic of natural primitive cells are prepared from poly(3-hexylthiophene)-block-poly(3-O-methacryloyl-D-galactopyranose) P3HT-b-PMAGP copolymers. The unique characteristic of such vesicular nanostructures is their architecture, which comprises a hydrophobic π-conjugated P3HT wall stabilized by a hydrophilic PMAGP interface featuring glucose units. The results of this work offer a very efficient and straightforward method for engineering well-controlled fluorescent nanoparticles (without the addition of dyes), which provide an excellent support to the study of carbohydrate-protein interactions.

Physicochemical properties of methylcellulose and dodecyltrimethylammonium bromide in aqueous medium.

Interactions between uncharged polymers and cationic surfactants are considered weaker than interactions with the anionic analogues. This work describes the binding occurring between methylcellulose (MC) and the cationic surfactant DTAB in aqueous medium. In the absence of salt, MC-DTAB exhibits a maximum in hydrodynamic radius, R(h,slow), with the increase in the surfactant concentration. Otherwise, in presence of salt the MC-DTAB system shows only a linear increase of R(h,slow). CAC is lower than the CMC, which is taken as an evidence of binding between the cationic surfactant and neutral polymer that induces the aggregation process. Static light scattering, rheology and micro-DSC results highlight the hydrophobic MC-DTAB association. Salt-out and the salt-in effects were observed in presence of DTAB, with a clear transition at concentration values close to the CMC, as judged from rheological and micro DSC measurements. Indeed, DTAB affects both the pattern of the sol-gel transition and the gel strength.

Structure of micelles formed by highly asymmetric polystyrene-b-polydimethylsiloxane and polystyrene-b-poly[5-(N,N-diethylamino)isoprene] diblock copolymers.

The internal structure of polystyrene(PS)-shell micelles having core-forming blocks consisting of polydimethylsiloxane (PDMS) or poly[5-(N,N-diethylamino)isoprene] (PAI) was determined in detail by accessing the multilevel structural organization using static and dynamic light scattering and small-angle X-ray scattering techniques. Well-defined PS-b-PDMS and PS-b-PAI diblock copolymers with molar masses in the range of 12.0k-18.2k g/mol were dispersed in cyclohexane, dimethylacetamide, or dimethylformamide. Colloidal nanoparticles exhibiting either swollen core with a large surface area per corona chain that enables the PS chains to assume a random coil conformation with gaussian statistics, or compact core and slightly stretched PS chains in the corona were obtained. Therefore, the results of this study provide an interesting alternative allowing for precise control of the core and corona properties of PS-b-PDMS and PS-b-PAI micelles in selective solvents. Admittedly, such differences in terms of micellar properties can dictate the potential of block copolymer micelles for generating thin films from preformed nano-objects, as well as the capability to function as nanoreactors in organic medium.

Block copolymer systems: from single chain to self-assembled nanostructures.

Recent advances in the field of macromolecular engineering applied to the fabrication of nanostructured materials using block copolymer chains as elementary building blocks are described in this feature article. By highlighting some of our work in the area and accounting for the contribution of other groups, we discuss the relationship between the physical-chemical properties of copolymer chains and the characteristics of nano-objects originating from their self-assembly in solution and in bulk, with emphasis on convenient strategies that allow for the control of composition, functionality, and topology at different levels of sophistication. In the case of micellar nanoparticles in solution, in particular, we present approaches leading to morphology selection via macromolecular architectural design, the functionalization of external solvent-philic shells with biomolecules (polysaccharides and proteins), and the maximization of micelle loading capacity by the suitable choice of solvent-phobic polymer segments. The fabrication of nanomaterials mediated by thin block copolymer films is also discussed. In this case, we emphasize the development of novel polymer chain manipulation strategies that ultimately allow for the preparation of precisely positioned nanodomains with a reduced number of defects via block-selective chemical reactivity. The challenges facing the soft matter community, the urgent demand to convert huge public and private investments into consumer products, and future possible directions in the field are also considered herein.

Aggregation of a versatile triblock copolymer into pH-responsive cross-linkable nanostructures in both organic and aqueous media.

The self-assembly of linear poly(ethylene oxide)-b-poly(glycerol monomethacrylate)-b-poly[2-(diisopropylamino)ethyl methacrylate] (PEO-b-PG2MA-b-PDPA) triblock copolymer into pH-responsive cross-linkable nanostructures in both organic and aqueous media is reported. Light scattering (LS), electron transmission microscopy (TEM), and nuclear magnetic resonance spectroscopy (NMR) techniques revealed that spherical particles with a core-shell architecture originated upon direct copolymer dissolution in THF, with PG2MA middle blocks occupying the nucleus, and PEO + PDPA segments forming the external layer. The hydroxylated core could be conveniently reticulated to form core cross-linked (CCL) micelles, which swelled without dissociating in presence of water at pH < pK(a) of amino groups. In the absence of stabilizing mechanisms (cross-links), the aggregates first disassembled in response to changes in the solvent selectivity due to water addition and eventually self-assembled again into spherical particles with a three-layered core-shell-corona structure. While pH-responsive PDPA segments were located at the core, PG2MA and PEO blocks composed the inner shell and corona, respectively. The interactions that facilitate micelle existence were reinforced by covalent cross-links in the PG2MA inner shell. Thus, depending on both the solution pH and the presence of cross-links, micelles exhibiting either pH-triggered or diffusion-controlled release mechanisms could be prepared. The encapsulation of enough amounts of guest molecules that interact strongly with the core-forming block led to the formation of cylindrical micelles. These results demonstrate that at least five different types of aggregates can be prepared from this versatile triblock copolymer, thus emphasizing the great potential of combining macromolecular design and sample manipulation strategies to devise functional nanostructures.

In vivo human electrochemical properties of a NiTi-based alloy (Nitinol) used for minimally invasive implants.

The development of a homemade device for in vivo human determination of the open circuit potential (OCP) of Nitinol is described. Pseudo-reference electrodes (316L stainless steel and Pt) were initially tested and validated in vitro using simulated body fluids. As judged from the excellent electrochemical responses in terms of both accuracy and precision, the most ideal system comprised the combination of sterilized Pt (pseudo-reference) and Nitinol (working) needle-shaped electrodes. The average in vivo human OCP determined from independent measurements on six human patients with indication of direct arterial surgery was -0.334 +/- 0.030 V/SCE. This value was in good agreement with data recorded in vitro using simulated body fluids (-0.313 +/- 0.003 V/SCE in AFNOR S90-701 artificial saliva; -0.334 +/- 0.001 V/SCE in artificial urine; -0.239 +/- 0.007 V/SCE in Ringer's solution). The thin surface film protecting the bulk NiTi alloy is therefore not susceptible to active dissolution at rest as long as the break down potentials (>>0.0 V/SCE) so far reported are well above OCP measured in this study. These results highlight the importance of evaluating the corrosion resistance of Nitinol under realistic conditions (mechanical loads, wear and fatigue) in order to establish multifaceted mechanisms that might lead to accelerated dissolution and failure of implanted stents.

Formation of annexin-a5 protein/block copolymer micelle complexes: QCM-D and PAGE experiments.

The Annexin-A5 (Anx5) protein is a specific marker of the exposure of phosphatidylserine molecules at the surface of cells, which occurs in processes such as apoptosis and platelet activation. Decoration of self-assembled block copolymer nanostructures by Anx5 is of particular interest in micelle-mediated target drug delivery or in vivo magnetic resonance imaging, the Anx5 imparting (bio)functionality to the system. In this work, the reversible binding of the Anx5 onto polystyrene-b-poly(2-phosphatethyl methacrylate-co-2-hydroxyethyl methacrylate) (PS-b-P(PEMA-co-HEMA)) block copolymer micelles in the presence of Ca2+ ions is described using Quartz crystal microbalance with dissipation monitoring (QCM-D) and polyacrylamide gel electrophoresis (PAGE) analysis. QCM-D experiments confirmed the binding process as well as its reversibility and dependence on the characteristics of macromolecular assemblies, such as the number of phosphonic diacid groups (Pmic) and hydrodynamic diameter (2RH). A linear relationship between the amount of micelles and the amount of protein bound onto the micelle surface until a saturation point was established by QCM-D. The amount of Anx5 bound to PS-b-P(PEMA-co-HEMA) micelles was successfully quantified by PAGE experiments in nondenaturing conditions, which also corroborated that the binding process is mediated by Ca2+ ions. The ability of such surface (bio)-functionalized nanoparticle systems to stabilize and transport hydrophobic loads was highlighted by transmission electron microscopy (TEM) of assemblies with entrapped iron oxide particles.

Specific interactions improve the loading capacity of block copolymer micelles in aqueous media.

Block copolymer micelles find application in many fields as nanocarriers, especially in drug delivery. We report herein that specific interactions between hydrophobic guest molecules and core-forming segments can significantly improve the loading capacity of polymeric micelles. High loading capacities (>100% weight/weight of polymer (w/wp)) were systematically observed for the encapsulation of probes containing weak carboxylic acid groups by micellar nanoparticles having poly[2-(dialkylamino)ethyl methacrylate] cores (i.e., particles whose cargo space exhibits antagonist weak base functions), as demonstrated by the incorporation of indomethacin (IND), ibuprofen (IBPF), and trans-3,5-bis(trifluoromethyl)cinnamic acid (F-CIN) into either poly(ethylene oxide)-b-poly[2-(diisopropylamino)ethyl methacrylate] (PEO-b-PDPA) or poly(glycerol monomethacrylate)-b-PDPA (PG2MA-b-PDPA) micelles. The esterification of IND yielding to a nonionizable IND ethyl ester derivative (IND-Et) caused an abrupt decrease in the micellar loading capacity down to 10-15% w/wp. Similar results were also obtained when IND was combined with nonionizable block copolymers such as PEO-b-polycaprolactone (PEO-b-PCL) and PEO-b-poly(glycidyl methacrylate) (PEO-b-PGMA). The existence of acid-base interactions between the solubilizate and the weak polybase block forming the micelle core was confirmed by 1H NMR measurements. However, the incorporation of high numbers of hydrophobic guest molecules inside polymeric micelles can provoke not only an increase in the hydrodynamic size (2RH) of the objects but also a substantial change in the morphology (transition from spheres to cylinders). The application of the Higuchi model showed that the probe release followed a diffusion-controlled mechanism, and diffusion coefficients (D) on the order of 10-18-10-17 cm2/s were determined for IND release from 1.0 mg/mL PEO113-b-PDPA50 + 100% w/wp IND. Probe release from micelles with weak polybase-based cores can also be triggered by changes in the solution pH.

Diblock copolymer micellar nanoparticles decorated with annexin-A5 proteins.

The formation of protein-decorated nanosized polymeric particles is described. Annexin-A5 protein binding to micellar aggregates having poly((1-ethoxycarbonyl)vinylphosphonic diacid) (PECVPD) and poly(n-butyl acrylate) (PBuA) as corona- and core-forming segments, respectively, was evidenced by Static and Dynamic Light Scattering (SDLS), cryo-Transmission Electron Microscopy (cryo-TEM), and Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) experiments. These new objects find potential applications, for example, in micelle-mediated target drug delivery and controlled fabrication of biochips.

Phosphorylcholine-based pH-responsive diblock copolymer micelles as drug delivery vehicles: light scattering, electron microscopy, and fluorescence experiments.

The micellization behavior of a diblock copolymer comprising a highly hydrophilic and biocompatible poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) corona-forming block and a pH-sensitive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) core-forming block (PMPC-b-PDPA) has been studied by static and dynamic light scattering (SDLS), transmission electron microscopy (TEM), and potentiometry. Self-assembly of PMPC-b-PDPA copolymers with two different DPA volume fractions (phi(DPA)) leads to narrowly distributed and structurally distinct spherical micelles, as evidenced by their molecular weight (M(w,mic)), aggregation number (N(agg)), hydrodynamic radius (R(H)), corona width (W), and core radius (R(c)). The excellent potential of these pH-responsive micelles as nanosized drug delivery vehicles was illustrated by the encapsulation of dipyridamole (DIP), a model hydrophobic drug that dissolves in acid solutions and becomes insoluble above pH 5.8, which is comparable to the pK(a) of the PDPA block. The influence of micelle structure (namely M(w,mic), N(agg), R(H), W, and R(c)) on drug loading content, drug loading efficiency, partition coefficient, and release kinetics was investigated and confirmed by fluorescence spectroscopy studies. The maximum dipyridamole loadings within PMPC(30)-b-PDPA(30) (R(H) = 14.0 nm; W = 4.8 nm; R(c) = 9.2 nm) and PMPC(30)-b-PDPA(60) (R(H) = 27.1 nm; W = 11.0 nm; R(c) = 16.1 nm) micelles were 7 and 12% w/w(p), respectively. This preferential solubilization of DIP into micelles formed by copolymer chains having longer core-forming blocks (i.e., possessing larger core volumes) reflects the larger partition coefficient (K(V)) of DIP between the aqueous phase and PMPC(30)-b-PDPA(60) micelles (K(V) = 5.7 x 10(4)) compared to PMPC(30)-b-PDPA(30) micelles (K(V) = 1.1 x 10(4)). This enhanced ability of PMPC(30)-b-PDPA(60) aggregates to entrap/stabilize small hydrophobic molecules also produces slower release kinetics. Rapid release can be triggered by lowering the pH to induce micellar dissociation.

Antioxidant activity of phenolic and related compounds: a density functional theory study on the O-H bond dissociation enthalpy.

We report here on calculations at the hybrid DFT/HF (B3-LYP/6-31G(d, p)) level of the O-H bond dissociation enthalpy (O-H BDE) of phenylpropenoic acids (caffeic, ferulic, p-coumaric and cinnamic) and phenolic acids and related compounds (gallic, methylgallate, vanillic and gentisic) in order to gain insight into the understanding of structure-antioxidant activity relationships. The results were correlated and discussed mainly on the basis of experimental data in a companion work (Galato D, Giacomelli C, Ckless K, Susin MF, Vale RMR, Spinelli A. Antioxidant capacity of phenolic and related compounds: correlation among electrochemical, visible spectroscopy methods and structure-antioxidant activity. Redox Report 2001; 6: 243-250). The O-H BDE values showed remarkable dependence on the hydroxyl position in the benzene ring and the existence of additional interaction due to hydrogen bonding. For parent molecules, the experimental antioxidant activity (AA) order was properly obeyed only when intramolecular hydrogen bonding was present in the radicalized structures of o-dihydroxyl moieties. In structurally related compounds, excellent correlation with experimental data was in general observed (0.64 < rho < 0.99). However, it is shown that excellent correlation can also be obtained for this series of compounds considering p-radicalized structures which were not stabilized by intramolecular hydrogen bonding, but this had no physical meaning. These findings suggested that the antioxidant activity evaluation of phenolic and related compounds must take into consideration the characteristics of each particular compound.