Elisa Lubian

Fullerene/Porphyrin Multicomponent Nanostructures on Ag(110): From Supramolecular Self-Assembly to Extended Copolymers

A novel two-step bottom-up approach to construct a 2D long-range ordered, covalently bonded fullerene/porphyrin binary nanostructure is presented: in the first place, reversible supramolecular interactions between C60 and 5,15-bis(4-aminophenyl)-10,20-diphenylporphyrin are exploited to obtain large domains of an ordered binary network, subsequently a reaction between fullerene molecules and the amino-groups residing on porphyrin units, triggered by thermal treatment, is used to freeze the supramolecular nanostructure with covalent bonds. The resulting nanostructure resists high temperature treatments as expected for an extended covalent network, whereas very similar fullerene/porphyrin nanostructures held together only by weak interactions are disrupted upon annealing at the same or at lower temperatures.

Bulky melamine-based Zn-porphyrin tweezer as a CD probe of molecular chirality†‡

The transfer of chirality from a guest molecule to an achiral host is the subject of significant interest especially when, upon chiral induction, the chiroptical response of the host/guest complex can effectively report the absolute configuration (AC) of the guest. For more than a decade, dimeric metalloporphyrin hosts (tweezers) have been successfully applied as chirality probes for determination of the AC for a wide variety of chiral synthetic compounds and natural products. The objective of this study is to investigate the utility of a new class of melamine-bridged Zn-porphyrin tweezers as sensitive AC reporters. A combined approach based on an experimental CD analysis and a theoretical prediction of the prevailing interporphyrin helicity demonstrates that these tweezers display favorable properties for chiral recognition. Herein, we discuss the application of the melamine-bridged tweezer to the chiral recognition of a diverse set of chiral guests, such as 1,2-diamines, α-amino-esters and amides, secondary alcohols, and 1,2-amino-alcohols. The bulky periphery and the presence of a rigid porphyrin linkage lead, in some cases, to a more enhanced CD sensitivity than that reported earlier with other tweezers.

Melamine-Bridged Bis(porphyrin-ZnII) Receptors: Molecular Recognition Properties

Dimeric metalloporphyrin hosts with tweezer-like structures have been synthesized by reacting the cyanuric chloride scaffold, CC, with 5-(4-aminophenyl)-10,15,20-triphenylporphyrin, P, and 5-(4-aminophenyl)-10,15,20-trimesitylporphyrin, M, to yield the homoconjugates free bases PP and MM and the heterodyad PM. Metalation with Zn(II), gives three structurally related ditopic receptors P(Zn)P(Zn), P(Zn)M(Zn), and M(Zn)M(Zn) with differential steric hindrance and conformational rigidity. The solution structure and supramolecular properties of these porphyrin dimers have been investigated as isolated molecules and in the presence of aliphatic alpha,omega-diamines of general formula H(2)N-(CH(2))(n)-NH(2) (n = 4-8) by spectroscopic and theoretical studies including multidimensional NMR, UV-vis, molecular modeling, and computational NMR methods. Binding constants in the range 4.2 x 10(6) to 3.4 x 10(7) M(-1) are observed in dichloromethane at 298 K, with a 3 orders of magnitude increase as compared to monodentate nBuNH(2), thus indicating the occurrence of a host-guest ditopic interaction. Linear correlation graphs are obtained by plotting the Soret band shift (Delta nu, cm(-1)) of the complex as a function of the diamine chain length. Combined NMR evidence and OPLS 2005 Force Field conformational analysis point to a mutual adaptation of both the binding partners in the host-guest complex, whose geometry is mainly dictated by the steric impact of the bulky substituents at the porphyrin periphery.

Stereoselective Photopolymerization of Tetraphenylporphyrin Derivatives on Ag(110) at the Sub-Monolayer Level

We explore a photochemical approach to achieve an ordered polymeric structure at the sub-monolayer level on a metal substrate. In particular, a tetraphenylporphyrin derivative carrying para-amino-phenyl functional groups is used to obtain extended and highly ordered molecular wires on Ag(110). Scanning tunneling microscopy and density functional theory calculations reveal that porphyrin building blocks are joined through azo bridges, mainly as cis isomers. The observed highly stereoselective growth is the result of adsorbate/surface interactions, as indicated by X-ray photoelectron spectroscopy. At variance with previous studies, we tailor the formation of long-range ordered structures by the separate control of the surface molecular diffusion through sample heating, and of the reaction initiation through light absorption. This previously unreported approach shows that the photo-induced covalent stabilization of self-assembled molecular monolayers to obtain highly ordered surface covalent organic frameworks is viable by a careful choice of the precursors and reaction conditions.

Variations of the corona HDL:albumin ratio determine distinct effects of amorphous SiO2 nanoparticles on monocytes and macrophages in serum

AIM We investigated monocyte and macrophage death and cytokine production induced by amorphous silica nanoparticles (SiO2-NPs) to clarify the role of defined serum corona proteins. MATERIALS & METHODS The cytotoxic proinflammatory effects of SiO2-NPs on human monocytes and macrophages were characterized in no serum, in fetal calf serum and in the presence of purified corona proteins. RESULTS In no serum and in fetal calf serum above approximately 75 µg/ml, SiO2-NPs lysed monocytes and macrophages by plasma membrane damage (necrosis). In fetal calf serum below approximately 75 µg/ml, SiO2-NPs triggered an endolysosomal acidification and caspase-1-dependent monocyte death (pyroptosis). The corona high-density lipoproteins:albumin ratio accounted for the features of the SiO2-NPs in serum. DISCUSSION Corona high-density lipoproteins are a major determinant of the differential cytotoxic action of SiO2-NPs on monocytes and macrophages.

STM investigation of temperature-dependent two-dimensional supramolecular architectures of C60 and amino-tetraphenylporphyrin on Ag(110).

Multicomponent supramolecular self-assemblies of exceptional long-range order and low defectivity are obtained if C(60) and 5-(4-aminophenyl)-10,15,20-triphenylporphyrin (TPP-NH2) are assembled on Ag(110) by sequential evaporation in the submonolayer range of TPP-NH2 and fullerene on the substrate surface and subsequent annealing. A (+/-2 -3, 6 +/- 3) array consisting of supramolecular stripes of a 1:1 C(60)/TPP-NH2 2D adduct develops at 410 K (the low temperature, LT, phase). If the LT phase is annealed at 470 K, then a 3:1 fullerene/TPP-NH2 (+/-3 -5, 5 +/- 5) nanoporous array (the HT phase) forms, with each pore containing a single porphyrin molecule. Phase separation occurs by annealing the HT phase at 520 K. Structural models are proposed and discussed on the basis of the experimental scanning tunneling microscopy results.

PEGylation of ORMOSIL nanoparticles differently modulates the in vitro toxicity toward human lung cells

AbstractORganically MOdified SILica (ORMOSIL) nanoparticles (NPs) appear promising carriers for the delivery of drugs to target tissues but concerns on possible cytotoxic effects exist. Here, we studied the in vitro responses to ORMOSIL NPs in different types of human lung cells to determine the effects of polyethylene glycol (PEG) coating on NP cytotoxicity. Non-PEG NPs caused a concentration-dependent decrease of viability of all types of cells, while PEG NPs induced deleterious effects and death in carcinoma alveolar type II A549 cells but not in CCD-34Lu fibroblasts and NCI-H2347 adenocarcinoma cells. Reactive oxygen species were detected in cells incubated with PEG NPs, but their deactivation by superoxide dismutase and catalase did not protect A549 cells from death, suggesting that the oxidative stress was not the main determinant of cytotoxicity. Only in A549 cells PEG NPs modulated the transcription of genes involved in inflammation, signal transduction and cell death. Transmission electron microscopy evidenced a unique intracellular localization of PEG NPs in the lamellar bodies of A549 cells, which could be the most relevant factor leading to cytotoxicity by reducing the production of surfactant proteins and by interfering with the pulmonary surfactant system.

C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes

Poly(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly(ethylene glycol) (PEG) for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA-engineered NPs have shown comparable pharmacokinetics and in vivo performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes, and macrophages and compared their performance with PEGylated and uncoated NP counterparts. Through detailed immunological and proteomic profiling, we show that PMOXA-coated NPs extensively trigger complement activation in human sera exclusively through the classical pathway. Complement activation is initiated by the sensing molecule C1q, where C1q binds with high affinity ( Kd = 11 ± 1 nM) to NP surfaces independent of immunoglobulin binding. C1q-mediated complement activation accelerates PMOXA opsonization with the third complement protein (C3) through the amplification loop of the alternative pathway. This promoted NP recognition by human blood leukocytes and monocyte-derived macrophages. The macrophage capture of PMOXA-coated NPs correlates with sera donor variability in complement activation and opsonization but not with other major corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps.

Preparation of ORMOSIL nanoparticles conjugated with vitamin D3 analogues and their biological evaluation

Dye-doped, 90 nm diameter, multifunctional organically modified silica (ORMOSIL) nanoparticles were prepared by condensation of vinyltriethoxysilane within surfactant-stabilized microemulsions and conjugated with several vitamin D3 derivatives. For this, vitamin D analogues possessing at least one hydroxyl group derivatized as vinylcarbonate have been synthesized. These analogues were conjugated to ORMOSIL nanoparticles through the carbonate function, forming carbamate derivatives of vitamin D nanoparticles. The interaction between these nanoparticles and human serum albumin, which is one of the serum transporters of the insoluble vitamin D3, was investigated by surface plasmon resonance. The results obtained revealed that this approach allows obtaining water-soluble vitamin D3 derivatives, which maintain their full protein binding ability.

Combined action of human commensal bacteria and amorphous silica nanoparticles on the viability and immune responses of dendritic cells

ABSTRACT Dendritic cells (DCs) regulate the host-microbe balance in the gut and skin, tissues likely exposed to nanoparticles (NPs) present in drugs, food, and cosmetics. We analyzed the viability and the activation of DCs incubated with extracellular media (EMs) obtained from cultures of commensal bacteria (Escherichia coli, Staphylococcus epidermidis) or pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus) in the presence of amorphous silica nanoparticles (SiO2 NPs). EMs and NPs synergistically increased the levels of cytotoxicity and cytokine production, with different nanoparticle dose-response characteristics being found, depending on the bacterial species. E. coli and S. epidermidis EMs plus NPs at nontoxic doses stimulated the secretion of interleukin-1β (IL-1β), IL-12, IL-10, and IL-6, while E. coli and S. epidermidis EMs plus NPs at toxic doses stimulated the secretion of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, and IL-5. On the contrary, S. aureus and P. aeruginosa EMs induced cytokines only when they were combined with NPs at toxic concentrations. The induction of maturation markers (CD86, CD80, CD83, intercellular adhesion molecule 1, and major histocompatibility complex class II) by commensal bacteria but not by pathogenic ones was improved in the presence of noncytotoxic SiO2 NP doses. DCs consistently supported the proliferation and differentiation of CD4+ and CD8+ T cells secreting IFN-γ and IL-17A. The synergistic induction of CD86 was due to nonprotein molecules present in the EMs from all bacteria tested. At variance with this finding, the synergistic induction of IL-1β was prevalently mediated by proteins in the case of E. coli EMs and by nonproteins in the case of S. epidermidis EMs. A bacterial costimulus did not act on DCs after adsorption on SiO2 NPs but rather acted as an independent agonist. The inflammatory and immune actions of DCs stimulated by commensal bacterial agonists might be altered by the simultaneous exposure to engineered or environmental NPs.