Effect of the Size and Shape of Dendronized Iron Oxide Nanoparticles Bearing a Targeting Ligand on MRI, Magnetic Hyperthermia, and Photothermia Properties-From Suspension to In Vitro Studies.

Functionalized iron oxide nanoparticles (IONPs) are increasingly being designed as a theranostic nanoplatform combining specific targeting, diagnosis by magnetic resonance imaging (MRI), and multimodal therapy by hyperthermia. The effect of the size and the shape of IONPs is of tremendous importance to develop theranostic nanoobjects displaying efficient MRI contrast agents and hyperthermia agent via the combination of magnetic hyperthermia (MH) and/or photothermia (PTT). Another key parameter is that the amount of accumulation of IONPs in cancerous cells is sufficiently high, which often requires the grafting of specific targeting ligands (TLs). Herein, IONPs with nanoplate and nanocube shapes, which are promising to combine magnetic hyperthermia (MH) and photothermia (PTT), were synthesized by the thermal decomposition method and coated with a designed dendron molecule to ensure their biocompatibility and colloidal stability in suspension. Then, the efficiency of these dendronized IONPs as contrast agents (CAs) for MRI and their ability to heat via MH or PTT were investigated. The 22 nm nanospheres and the 19 nm nanocubes presented the most promising theranostic properties (respectively, r2 = 416 s-1·mM-1, SARMH = 580 W·g-1, SARPTT = 800 W·g-1; and r2 = 407 s-1·mM-1, SARMH = 899 W·g-1, SARPTT = 300 W·g-1). MH experiments have proven that the heating power mainly originates from Brownian relaxation and that SAR values can remain high if IONPs are prealigned with a magnet. This raises hope that heating will maintain efficient even in a confined environment, such as in cells or in tumors. Preliminary in vitro MH and PTT experiments have shown the promising effect of the cubic shaped IONPs, even though the experiments should be repeated with an improved set-up. Finally, the grafting of a specific peptide (P22) as a TL for head and neck cancers (HNCs) has shown the positive impact of the TL to enhance IONP accumulation in cells.

Magnetic Nanoclusters Stabilized with Poly[3,4-Dihydroxybenzhydrazide] as Efficient Therapeutic Agents for Cancer Cells Destruction.

Magnetic structures exhibiting large magnetic moments are sought after in theranostic approaches that combine magnetic hyperthermia treatment (MH) and diagnostic magnetic resonance imaging in oncology, since they offer an enhanced magnetic response to an external magnetic field. We report on the synthesized production of a core-shell magnetic structure using two types of magnetite nanoclusters (MNC) based on a magnetite core and polymer shell. This was achieved through an in situ solvothermal process, using, for the first time, 3,4-dihydroxybenzhydrazide (DHBH) and poly[3,4-dihydroxybenzhydrazide] (PDHBH) as stabilizers. Transmission electron microscopy (TEM) analysis showed the formation of spherical MNC, X-ray photoelectronic spectroscopy (XPS) and Fourier transformed infrared (FT-IR) analysis proved the existence of the polymer shell. Magnetization measurement showed saturation magnetization values of 50 emu/g for PDHBH@MNC and 60 emu/g for DHBH@MNC with very low coercive field and remanence, indicating that the MNC are in a superparamagnetic state at room temperature and are thus suitable for biomedical applications. MNCs were investigated in vitro, on human normal (dermal fibroblasts-BJ) and tumor (colon adenocarcinoma-CACO2, and melanoma-A375) cell lines, in view of toxicity, antitumor effectiveness and selectivity upon magnetic hyperthermia. MNCs exhibited good biocompatibility and were internalized by all cell lines (TEM), with minimal ultrastructural changes. By means of flowcytometry apoptosis detection, fluorimetry, spectrophotometry for mitochondrial membrane potential, oxidative stress, ELISA-caspases, and Western blot-p53 pathway, we show that MH efficiently induced apoptosis mostly via the membrane pathway and to a lower extent by the mitochondrial pathway, the latter mainly observed in melanoma. Contrarily, the apoptosis rate was above the toxicity limit in fibroblasts. Due to its coating, PDHBH@MNC showed selective antitumor efficacy and can be further used in theranostics since the PDHBH polymer provides multiple reaction sites for the attachment of therapeutic molecules.

Doxorubicin Loaded Thermosensitive Magneto-Liposomes Obtained by a Gel Hydration Technique: Characterization and In Vitro Magneto-Chemotherapeutic Effect Assessment.

The combination of magnetic hyperthermia with chemotherapy is considered a promising strategy in cancer therapy due to the synergy between the high temperatures and the chemotherapeutic effects, which can be further developed for targeted and remote-controlled drug release. In this paper we report a simple, rapid, and reproducible method for the preparation of thermosensitive magnetoliposomes (TsMLs) loaded with doxorubicin (DOX), consisting of a lipidic gel formation from a previously obtained water-in-oil microemulsion with fine aqueous droplets containing magnetic nanoparticles (MNPs) dispersed in an organic solution of thermosensitive lipids (transition temperature of ~43 °C), followed by the gel hydration with an aqueous solution of DOX. The obtained thermosensitive magnetoliposomes (TsMLs) were around 300 nm in diameter and exhibited 40% DOX incorporation efficiency. The most suitable MNPs to incorporate into the liposomal aqueous lumen were Zn ferrites, with a very low coercive field at 300 K (7 kA/m) close to the superparamagnetic regime, exhibiting a maximum absorption rate (SAR) of 1130 W/gFe when dispersed in water and 635 W/gFe when confined inside TsMLs. No toxicity of Zn ferrite MNPs or of TsMLs was noticed against the A459 cancer cell line after 48 h incubation over the tested concentration range. The passive release of DOX from the TsMLs after 48h incubation induced a toxicity starting with a dosage level of 62.5 ug/cm2. Below this threshold, the subsequent exposure to an alternating magnetic field (20-30 kA/m, 355 kHz) for 30 min drastically reduced the viability of the A459 cells due to the release of incorporated DOX. Our results strongly suggest that TsMLs represent a viable strategy for anticancer therapies using the magnetic field-controlled release of DOX.

Enhanced Magnetic Hyperthermia Performance of Zinc Ferrite Nanoparticles under a Parallel and a Transverse Bias DC Magnetic Field.

The collective organization of magnetic nanoparticles (MNPs) influences significantly their hyperthermic properties, relevant for their in vitro and in vivo applications. We report a systematic investigation of the effects of the concentration and the static bias direct current (DC) magnetic field superposed over the alternating magnetic field (AMF), both in a parallel and perpendicular configuration, on the specific absorption rate (SAR) by using zinc ferrite MNPs. The nonmonotonic dependence of the SAR on the concentration, with a maximum at very small concentrations (c ≤ 0.1 mgFe/mL), followed by a minimum at 0.25 mgFe/mL, and the second maximum of 3.3 kW/gFe at around 1 mgFe/mL, was explained by the passage of the MNPs from a single particle behavior to a collective one and the role of the dipolar interactions. By superposing a static 10 kA/m bias DC field on the AMF we obtained an increase in the SAR for both parallel and perpendicular orientations, up to 4285 W/gFe and 4070 W/gFe, respectively. To the best of our knowledge, this is the first experimental proof of a significant enhancement of the SAR produced by a perpendicular DC field. The effect of the DC field to increase the SAR is accompanied by an increase in the hyperthermia coercive field (HcHyp) for both configurations. No enhancement of the DC fields was noticed for the MNPs immobilized in a solid matrix but the DC field increases the HcHyp only in the parallel configuration. This translates into a higher SAR value for the perpendicular configuration as compared to the parallel configuration. These results have practical applications for magnetic hyperthermia.

A Fast, Reliable Oil-In-Water Microemulsion Procedure for Silica Coating of Ferromagnetic Zn Ferrite Nanoparticles Capable of Inducing Cancer Cell Death In Vitro.

The applications of ferrimagnetic nanoparticles (F-MNPs) in magnetic hyperthermia (MH) are restricted by their stabilization in microscale aggregates due to magnetostatic interactions significantly reducing their heating performances. Coating the F-MNPs in a silica layer is expected to significantly reduce the magnetostatic interactions, thereby increasing their heating ability. A new fast, facile, and eco-friendly oil-in-water microemulsion-based method was used for coating Zn0.4Fe2.6O4 F-MNPs in a silica layer within 30 min by using ultrasounds. The silica-coated clusters were characterized by various physicochemical techniques and MH, while cytotoxicity studies, cellular uptake determination, and in vitro MH experiments were performed on normal and malignant cell lines. The average hydrodynamic diameter of silica-coated clusters was approximately 145 nm, displaying a high heating performance (up to 2600 W/gFe). Biocompatibility up to 250 µg/cm2 (0.8 mg/mL) was recorded by Alamar Blue and Neutral Red assays. The silica-coating increases the cellular uptake of Zn0.4Fe2.6O4 clusters up to three times and significantly improves their intracellular MH performances. A 90% drop in cellular viability was recorded after 30 min of MH treatment (20 kA/m, 355 kHz) for a dosage level of 62.5 µg/cm2 (0.2 mg/mL), while normal cells were more resilient to MH treatment.

The Influence of Zn Substitution on Physical Properties of CoFe2O4 Nanoparticles.

Co1−xZnxFe2O4 nanoparticles (0 ≤ x ≤ 1) have been synthesized via a green sol−gel combustion method. The prepared samples were studied using X-ray diffraction measurements (XRD), transmission electron microscopy (TEM), Raman, and magnetic measurements. All samples were found to be single phases and have a cubic Fd-3m structure. EDS analysis confirmed the presence of cobalt, zinc, iron, and oxygen in all studied samples. Raman spectra clearly show that Zn ions are preferentially located in T sites for low Zn concentrations. Due to their high crystallinity, the nanoparticles show high values of the magnetization, which increases with the Zn content for x < 0.5. The magnetic properties are discussed based on Raman results. Co ferrite doped with 30% of Zn produced the largest SAR values, which increase linearly from 148 to 840 W/gMNPs as the H is increased from 20 to 60 kA/m.

The Effect of Zn-Substitution on the Morphological, Magnetic, Cytotoxic, and In Vitro Hyperthermia Properties of Polyhedral Ferrite Magnetic Nanoparticles.

The clinical translation of magnetic hyperthermia (MH) needs magnetic nanoparticles (MNPs) with enhanced heating properties and good biocompatibility. Many studies were devoted lately to the increase in the heating power of iron oxide MNPs by doping the magnetite structure with divalent cations. A series of MNPs with variable Zn/Fe molar ratios (between 1/10 and 1/1) were synthesized by using a high-temperature polyol method, and their physical properties were studied with different techniques (Transmission Electron Microscopy, X-ray diffraction, Fourier Transform Infrared Spectroscopy). At low Zn doping (Zn/Fe ratio 1/10), a significant increase in the saturation magnetization (90 e.m.u./g as compared to 83 e.m.u./g for their undoped counterparts) was obtained. The MNPs' hyperthermia properties were assessed in alternating magnetic fields up to 65 kA/m at a frequency of 355 kHz, revealing specific absorption rates of up to 820 W/g. The Zn ferrite MNPs showed good biocompatibility against two cell lines (A549 cancer cell line and BJ normal cell line) with a drop of only 40% in the viability at the highest dose used (500 µg/cm2). Cellular uptake experiments revealed that the MNPs enter the cells in a dose-dependent manner with an almost 50% higher capacity of cancer cells to accommodate the MNPs. In vitro hyperthermia data performed on both cell lines indicate that the cancer cells are more sensitive to MH treatment with a 90% drop in viability after 30 min of MH treatment at 30 kA/m for a dose of 250 µg/cm2. Overall, our data indicate that Zn doping of iron oxide MNPs could be a reliable method to increase their hyperthermia efficiency in cancer cells.

Quantitative Analysis of the Specific Absorption Rate Dependence on the Magnetic Field Strength in ZnxFe3-xO4 Nanoparticles.

Superparamagnetic ZnxFe3-xO4 magnetic nanoparticles (0 ≤ x < 0.5) with spherical shapes of 16 nm average diameter and different zinc doping level have been successfully synthesized by co-precipitation method. The homogeneous zinc substitution of iron cations into the magnetite crystalline structure has led to an increase in the saturation magnetization of nanoparticles up to 120 Am2/kg for x ~ 0.3. The specific absorption rate (SAR) values increased considerably when x is varied between 0 and 0.3 and then decreased for x ~ 0.5. The SAR values are reduced upon the immobilization of the nanoparticles in a solid matrix being significantly increased by a pre-alignment step in a uniform static magnetic field before immobilization. The SAR values displayed a quadratic dependence on the alternating magnetic field amplitude (H) up to 35 kA/m. Above this value, a clear saturation effect of SAR was observed that was successfully described qualitatively and quantitatively by considering the non-linear field's effects and the magnetic field dependence of both Brown and Neel relaxation times. The Neel relaxation time depends more steeply on H as compared with the Brown relaxation time, and the magnetization relaxation might be dominated by the Neel mechanism, even for nanoparticles with large diameter.

In Vitro Intracellular Hyperthermia of Iron Oxide Magnetic Nanoparticles, Synthesized at High Temperature by a Polyol Process.

We report the synthesis of magnetite nanoparticles (IOMNPs) using the polyol method performed at elevated temperature (300 °C) and high pressure. The ferromagnetic polyhedral IOMNPs exhibited high saturation magnetizations at room temperature (83 emu/g) and a maximum specific absorption rate (SAR) of 2400 W/gFe in water. The uniform dispersion of IOMNPs in solid matrix led to a monotonous increase of SAR maximum (3600 W/gFe) as the concentration decreased. Cytotoxicity studies on two cell lines (cancer and normal) using Alamar Blues and Neutral Red assays revealed insignificant toxicity of the IOMNPs on the cells up to a concentration of 1000 µg/mL. The cells internalized the IOMNPs inside lysosomes in a dose-dependent manner, with higher amounts of IOMNPs in cancer cells. Intracellular hyperthermia experiments revealed a significant increase in the macroscopic temperatures of the IOMNPs loaded cell suspensions, which depend on the amount of internalized IOMNPs and the alternating magnetic field amplitude. The cancer cells were found to be more sensitive to the intracellular hyperthermia compared to the normal ones. For both cell lines, cells heated at the same macroscopic temperature presented lower viability at higher amplitudes of the alternating magnetic field, indicating the occurrence of mechanical or nanoscale heating effects.

Hyperthermia, Cytotoxicity, and Cellular Uptake Properties of Manganese and Zinc Ferrite Magnetic Nanoparticles Synthesized by a Polyol-Mediated Process.

Manganese and zinc ferrite magnetic nanoparticles (MNPs) were successfully synthesizedusing the polyol method in ethylene glycol and were found to have high saturation magnetizationvalues (90-95 emu/g at 4 K) when formed by ~30-nm crystallites assembled in an ~80-nm multicorestructure. Hyperthermia data revealed a sigmoidal dependence of the specific absorption rate (SAR)on the alternating magnetic field (AMF) amplitude, with remarkable saturation SAR values in waterof ~1200 W/gFe+Mn and ~800 W/gFe+Zn for the Mn and Zn ferrites, respectively. The immobilizationof the MNPs in a solid matrix reduced the maximum SAR values by ~300 W/gFe+Mn, Zn for bothferrites. The alignment of the MNPs in a uniform static magnetic field, before their immobilizationin a solid matrix, significantly increased their heating performance. Toxicity assays performed infour cell lines revealed a lower toxicity for the Mn ferrites, while in the case of the Zn ferrites, only~50% of cells were viable upon their incubation for 24 h with 0.2 mg/mL of MNPs. Cellular uptakeexperiments revealed that both MNPs entered the cells in a time-dependent manner, as they werefound initially in endosomes and later in the cytosol. All of the studied cell lines were more sensitiveto the ZnFe2O4 MNPs.

Origanum vulgare mediated green synthesis of biocompatible gold nanoparticles simultaneously possessing plasmonic, antioxidant and antimicrobial properties.

PURPOSE: The leaves and flowering stem of Origanum vulgare contain essential oils, flavonoids, phenolic acids and anthocyanins. We propose a new, simple, one-pot, O. vulgare extract (OVE) mediated green synthesis method of biocompatible gold nanoparticles (AuNPs) possessing improved antioxidant, antimicrobial and plasmonic properties. MATERIALS AND METHODS: Different concentrations of OVEs were used to reduce gold ions and to synthetize biocompatible spherical AuNPs. Their morphology and physical properties have been investigated by means of transmission electron microscopy, ultraviolet-visible absorption spectroscopy, photon correlation spectroscopy and Fourier transform infrared spectroscopy, whereas their plasmonic properties have been tested using surface-enhanced Raman spectroscopy (SERS). The antioxidant properties of nanoparticles (NPs) have been evaluated by 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, and the antimicrobial tests were performed using the disk diffusion assay. Their cytotoxicity has been assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS: The experimental results confirmed the successful synthesis of biocompatible, spherical, plasmonic NPs having a mean diameter of ~40 nm and an outstanding aqueous stability. This new class of NPs exhibits a very good antioxidant activity and presents interesting inhibitory effects against Staphylococcus aureus and Candida albicans. Due to their plasmonic properties, AuNPs are used as SERS substrates for the detection of a test molecule (methylene blue) up to a concentration of 10-7 M and a pharmaceutical compound (propranolol) in solution. Cytotoxicity assays revealed that AuNPs are better tolerated by normal human dermal fibroblast cells, while the melanoma cancer cells are more sensitive. CONCLUSION: The biocompatible AuNPs synthetized using OVEs showed significant bactericidal and antimycotic activities, the most sensitive microorganisms being S. aureus and C. albicans, both commonly involved in various dermatological infections. Moreover, the significant antioxidant effect might recommend their use for protective and/or preventive effect in various skin inflammatory conditions, including the reduction in side effects in dermatological infections. Meanwhile, the as-synthesized biocompatible AuNPs can be successfully used as SERS substrates for the detection of pharmaceutical compounds in aqueous solutions.

Small versus Large Iron Oxide Magnetic Nanoparticles: Hyperthermia and Cell Uptake Properties.

Efficient use of magnetic hyperthermia in clinical cancer treatment requires biocompatible magnetic nanoparticles (MNPs), with improved heating capabilities. Small (~34 nm) and large (~270 nm) Fe3O4-MNPs were synthesized by means of a polyol method in polyethylene-glycol (PEG) and ethylene-glycol (EG), respectively. They were systematically investigated by means of X-ray diffraction, transmission electron microscopy and vibration sample magnetometry. Hyperthermia measurements showed that Specific Absorption Rate (SAR) dependence on the external alternating magnetic field amplitude (up to 65 kA/m, 355 kHz) presented a sigmoidal shape, with remarkable SAR saturation values of ~1400 W/gMNP for the small monocrystalline MNPs and only 400 W/gMNP for the large polycrystalline MNPs, in water. SAR values were slightly reduced in cell culture media, but decreased one order of magnitude in highly viscous PEG1000. Toxicity assays performed on four cell lines revealed almost no toxicity for the small MNPs and a very small level of toxicity for the large MNPs, up to a concentration of 0.2 mg/mL. Cellular uptake experiments revealed that both MNPs penetrated the cells through endocytosis, in a time dependent manner and escaped the endosomes with a faster kinetics for large MNPs. Biodegradation of large MNPs inside cells involved an all-or-nothing mechanism.

Polyethylene Glycol-Mediated Synthesis of Cubic Iron Oxide Nanoparticles with High Heating Power.

Iron oxide magnetic nanoparticles (IOMNPs) have been successfully synthesized by means of solvothermal reduction method employing polyethylene glycol (PEG200) as a solvent. The as-synthesized IOMNPs are poly-dispersed, highly crystalline, and exhibit a cubic shape. The size of IOMNPs is strongly dependent on the reaction time and the ration between the amount of magnetic precursor and PEG200 used in the synthesis method. At low magnetic precursor/PEG200 ratio, the cubic IOMNPs coexist with polyhedral IOMNPs. The structure and morphology of the IOMNPs were thoroughly investigated by using a wide range of techniques: TEM, XRD, XPS, FTIR, and RAMAN. XPS analysis showed that the IOMNPs comprise a crystalline magnetite core bearing on the outer surface functional groups from PEG200 and acetate. The presence of physisorbed PEG200 on the IOMNP surface is faintly detected through FT-IR spectroscopy. The surface of IOMNPs undergoes oxidation into maghemite as proven by RAMAN spectroscopy and the occurrence of satellite peaks in the Fe2p XP spectra. The magnetic studies performed on powder show that the blocking temperature (TB) of IOMNPs is around 300 K displaying a coercive field in between 160 and 170 Oe. Below the TB, the field-cooled (FC) curves turn concave and describe a plateau indicating that strong magnetic dipole-dipole interactions are manifested in between IOMNPs. The specific absorption rate (SAR) values increase with decreasing nanoparticle concentrations for the IOMNPs dispersed in water. The SAR dependence on the applied magnetic field, studied up to magnetic field amplitude of 60 kA/m, presents a sigmoid shape with saturation values up to 1700 W/g. By dispersing the IOMNPs in PEG600 (liquid) and PEG1000 (solid), it was found that the SAR values decrease by 50 or 75 %, indicating that the Brownian friction within the solvent was the main contributor to the heating power of IOMNPs.

A new class of pegylated plasmonic liposomes: synthesis and characterization.

The multifunctional nanoobjects that can be controlled, manipulated and triggered using external stimuli represent very promising candidates for nanoscale therapeutic and diagnostic applications. In this study we report the successful synthesis and characterization of a new class of very stable multifunctional nanoobjects, containing cationic liposomes decorated with PEGylated gold nanoparticles (PEGAuNPs). The multifunctional hybrid nanoobjects (mHyNp) were prepared by taking advantage of the electrostatic interactions between small unilamelar cationic liposomes and negatively charged gold nanoparticles. The mHyNps have been investigated by UV-VIS absorption spectroscopy, Dynamic Light Scattering (DLS), Zeta Potential Measurements and Transmission Electron Microscopy (TEM). The TEM images clearly revealed the attachment of individual gold nanoparticles onto the spherical outer surface of the cationic liposomes which was also confirmed by DLS and UV-VIS data. Furthermore, the plasmonic properties of the hybrid complexes have been evaluated by using the Surface Enhanced Raman Spectroscopy (SERS) technique. It is shown that PEG mediated interaction between the liposomes and the gold nanoparticles enabled the recording of the SER spectra of the liposomes in aqueous environment, thus demonstrating the plasmonic properties of the hybrids.

Surface mediated chiral interactions between cyclodextrins and propranolol enantiomers: a SERS and DFT study.

The nanoparticles mediated enantioselective recognition of propranolol enantiomers through native cyclodextrin complexation has been investigated by using surface-enhanced Raman spectroscopy (SERS). The highly efficient chiral recognition mechanism is based on a synergistic interaction between spherical noble metal nanoparticles, propranolol enantiomers and native cyclodextrins (CDs). Amongst the native cyclodextrins, ß-CD has the highest chiral recognition ability for propranolol enantiomers, due to its specific shape and cavity size, thus producing the largest difference between the recorded SERS spectra of the two hosted enantiomers. The molecular interaction mechanism responsible for enantioselectivity was furthermore proven by quantum chemical calculations based on density functional theory (DFT). The theoretical calculations and experimental SER spectra allowed the assignment of functional moieties involved in the chiral recognition mechanism. The most important factors governing the highly efficient chiral probing by SERS are the fundamentally different mechanism of interaction between the R- and S-enantiomers and ß-CD and the strength of interaction between the nanoparticle surface and the two propranolol-CD complexes. The role of metallic nanoparticles in the enantioselective recognition process has been experimentally evaluated by using silver and gold nanoparticles as SERS substrates, given their ability to interact differently with the complexes. The viability of this new method for chiral discrimination has been demonstrated for both substrates and could open new avenues for these kinds of applications.

SERS-active silver colloids prepared by reduction of silver nitrate with short-chain polyethylene glycol.

We report a fast, one-step, facile, and green preparation method that yields very stable and biocompatible silver colloids that are highly active as surface-enhanced Raman spectroscopy (SERS) platforms that has a possible application in biomedicine. Reduction of silver nitrate has been carried out using polyethylene glycol (PEG) which acts as both reducing agent and stabilizer. It turned out that the -OH groups provided by the addition of NaOH represent a key element in the successful synthesis of PEG-coated silver nanoparticles (AgNPs). The as-obtained silver colloids have been characterized by UV-visible spectroscopy, transmission electron spectroscopy, and SERS using 532- and 633-nm laser lines on a dispersive Raman spectrometer. Several analytes as methylene blue, p-aminothiophenol, amoxicillin, and Cu(PAR)2 were used to prove SERS enhancement of the obtained silver colloid. It has been found that the PEGylated AgNPs provide SERS signals comparable to those achieved using classical hydroxylamine and citrate-reduced silver colloids, thus demonstrating the ability of this new method to prepare biocompatible silver colloids.

Controlling the dimensionality and structure of supramolecular porphyrin assemblies by their functional substituents: dimers, chains, and close-packed 2D assemblies.

Repulsive interactions: a staging of supramolecular aggregation from (0D) clusters to (1D) chains and (2D) assemblies as a function of molecular coverage of dipolar porphyrins adsorbed on the Ag(111) surface is described. It displays a complex interplay of both attractive and repulsive molecule-molecule interactions, the emergence of chirality, and the registry of the substrate.

Assembly of 2D ionic layers by reaction of alkali halides with the organic electrophile 7,7,8,8-tetracyano-p-quinodimethane (TCNQ).

Sublimation of alkali halides (NaCl and LiCl) onto a pre-assembled hydrogen-bonded layer of TCNQ on Au(111) resulted in the formation of 2D ionic layers via a direct charge-transfer reaction without involvement of the substrate. The presented approach allows for the fabrication of different ionic layers, decoupled from the substrate and offering new, potentially interesting properties.

Controlling spins in adsorbed molecules by a chemical switch.

The development of chemical systems with switchable molecular spins could lead to the architecture of materials with controllable magnetic or spintronic properties. Here, we present conclusive evidence that the spin of an organometallic molecule coupled to a ferromagnetic substrate can be switched between magnetic off and on states by a chemical stimulus. This is achieved by nitric oxide (NO) functioning as an axial ligand of cobalt(II)tetraphenylporphyrin (CoTPP) ferromagnetically coupled to nickel thin-film (Ni(001)). On NO addition, the coordination sphere of Co(2+) is modified and a NO-CoTPP nitrosyl complex is formed, which corresponds to an off state of the Co spin. Thermal dissociation of NO from the nitrosyl complex restores the on state of the Co spin. The NO-induced reversible off-on switching of surface-adsorbed molecular spins observed here is attributed to a spin trans effect.