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Antibiotic resistance is currently a global health emergency. Metallodrugs, especially metal coordination complexes, comprise a broad variety of candidates to combat antibacterial infections. In this work, we designed a new family of Schiff base zinc(II) complexes with iminopyridine as an organic ligand and different inorganic ligands: chloride, nitrate, and acetate. The antibacterial effect of the Zn(II) complexes was studied against planktonic bacterial cells of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) strains. The results showed a moderate biocide activity in both types of planktonic bacteria, which arises from the metal complexation to the Schiff base ligand. Importantly, we confirmed the crucial effect of the metal, with Zn(II) improving the activity of Cu(II) counterparts previously reported. On the other hand, the impact of the inorganic ligands was not significant for the antibacterial effect but was relevant for the complex solubility. Finally, as proof of concept of topical antibacterial formulation, we formulated an emulsion containing the most lipophilic Zn(II) complex and confirmed a sustained release for 24 h in a vertical cell diffusion assay. The promising activity of iminopyridine Zn(II) complexes is potentially worth exploring in more detailed studies.

Dendritic hydrogels based on carbosilane crosslinkers are promising drug delivery systems, as their amphiphilic nature improves the compatibility with poorly water-soluble drugs. In this work, we explored the impact of the complementary polymer on the amphiphilic properties of the dendritic network. Different polymers were selected as precursors, from the highly lipophilic propylene glycol (PPG) to the hydrophilic polyethylene glycol (PEG), including amphiphilic Pluronics L31, L35 and L61. The dithiol polymers reacted with carbosilane crosslinkers through UV-initiated thiol-ene coupling (TEC), and the resultant materials were classified as non-swelling networks (for PPG, PLU L31 and PLU L61 ) and high-swelling hydrogels (for PEG and PLU L35 ). The hydrogels exhibited thermo-responsive properties, shrinking at higher temperatures, and exhibited an intriguing drug release pattern due to internal nanostructuring. Furthermore, we fine-tuned the dendritic crosslinker, including hydroxyl and azide pendant groups in the focal point, generating functional networks that can be modified through degradable (ester) and non-degradable (triazol) bonds. Overall, this work highlighted the crucial role of the amphiphilic balance in the design of dendritic hydrogels with thermo-responsive behavior and confirmed their potential as functional networks for biomedical applications.

Soft gelatin capsules (SGCs) are the most widely used pharmaceutical form after tablets. The active components, active pharmaceutical ingredients (APIs), or nutrients are dissolved, dispersed, or suspended in a liquid or semisolid fill, which is covered with a gelatin shell. Several factors can modify the properties of the gelatin shell and subsequently affect their operative handling during manufacturing process and the stability of the soft gelatin capsules. Three elements appear to be crucial: the shell formulation (type and content of the different components such as gelatins-source, extraction method-plasticizers, or additives); the manufacture and storage conditions (temperature, humidity, light) as well as the interactions between fill-shell formulas. Mechanical and thermal analysis arise as straightforward but highly useful tools to monitor the properties of the gelatin shell. This review provides an updated overview on the shell formulation and design. Additionally, it presents the uses of mechanical and thermal techniques to characterize and evaluate the impact of different parameters on the gelatin behavior over the production and stability of these pharmaceutical forms. This will help to detect changes that are yet not visible by visual inspection ensuring a suitable finished product over its shelf-life., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

The emergence of antibiotic resistance is a serious global health problem. There is an incessant demand for new antimicrobial drugs and materials that can address this global issue from different angles. Dendritic hydrogels have appeared as a promising strategy. A family of bifunctional amphiphilic carbosilane dendrimers was designed and employed as nanosized cross-linking points for the synthesis of high-swelling hydrogels using the highly efficient Thiol-Ene click reaction for their preparation. Both stoichiometric and off-stoichiometric conditions were studied, generating hydrogels with pendant hydroxyl or alkene moieties. These hydrogels were found to be tunable antibacterial materials. They can easily be postmodified with relevant antibiotic moieties through covalent attachment on the hydroxyl or alkene pendant groups, generating ammonium-decorated networks with temperature and pH-responsive properties. Additionally, they can efficiently encapsulate drugs with poor solubility in water, like ciprofloxacin, and perform a sustained release over time, as demonstrated in preliminary assays against Staphylococcus aureus ., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Carbosilane dendrimers are hyperbranched lipophilic scaffolds widely explored in biomedical applications. This work exploits, for the first time, the ability of these scaffolds to generate functional hydrogels with amphiphilic properties. The monodispersity and multivalency enable a precise synthetic control of the network, while the lipophilicity improves the compatibility with poorly soluble cargo. The first family of cleavable carbosilane dendrimers was designed for this purpose, overcoming one of the main drawbacks of these type of dendrimers. Biodegradable dendritic low-swelling hydrogels with aromatic nanodomains were easily prepared using the highly efficient click thiol-ene chemistry. Our studies through electron-paramagnetic resonance, molecular dynamics simulations, and experimental assays confirmed the impact of the carbosilane dendritic nanodomains in both the encapsulation and the release pattern of model drugs such as ibuprofen and curcumin. Curcumin-loaded hydrogels were further tested in in vitro assays against advanced prostate cancer cells. The dendritic hydrogels not only enabled drugs encapsulation; as proof of concept, ibuprofen was efficiently attached via fluoride-promoted esterification and was enzymatically cleaved, achieving a controlled release over time., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Pluronics are a family of amphiphilic block copolymers broadly explored in the pharmaceutical field. Under certain conditions, Pluronics self-assemble in different structures including nanosized direct and reverse micelles. This review provides an overview about the main parameters affecting the micellization process of Pluronics, such as polymer length, fragments distribution within the chain, solvents, additives and loading of cargo. Furthermore, it offers a guide about the most common techniques used to characterize the structure and properties of the micelles. Finally, it presents up-to-date approaches to improve the stability and drug loading of Pluronic micelles. Special attention is paid to reverse Pluronics and reverse micelles, currently underexplored in the literature. Pluronic micelles present a bright future as drug delivery agents. A smart design and thorough characterization will improve the transfer to clinical applications.

Biofilm formation is a critical health concern, involved in most human bacterial infections. Combatting this mechanism, which increases resistance to traditional antibiotics and host immune defences, requires novel therapeutic approaches. The remarkable biocide activity and the monodispersity of carbosilane metallodendrimers make them excellent platforms to evaluate the impact of different structural parameters on the biological activity. In this work, we explore the influence of iminopyridine ring substituents on the antibacterial activity against planktonic and biofilm Staphylococcus aureus . New families of first-generation Ru(II) and Cu(II) metallodendrimers were synthesised and analysed, in comparison to the non-substituted counterparts. The results showed that the presence of methyl or methoxy groups in meta position to the imine bond decreased the overall positive charge on the metal ion and, subsequently, the activity against planktonic bacteria. However, it seemed a relevant parameter to consider for the prevention of biofilm formation, if they contribute to increasing the overall lipophilicity. An optimum balance of the charge and lipophilicity of the metallodrug, accomplished through structural design, will provide effective biocide agents against bacteria biofilms.

Bacterial infections are one of the major threats to human health due to the raising crisis of antibiotic resistance. Herein, second generation antibacterial heterofunctional dendrimers based on 2,2-bis(methylol)propionic acid were synthesized. The dendrimers possessed six alkenes and 12 ammonium end-groups per molecule and were used to fabricate antibacterial hydrogels together with dithiol-functional polyethylene glycol (mol wt of 2, 6 and 10 kDa) as crosslinkers via thiol-ene chemistry. The network formation can be completed within 10 s upon UV-irradiation as determined by the stabilization of the storage modulus in a rheometer. The hydrogels swelled in aqueous media and could be functionalized with the N-hydroxysuccinimide ester of the dye disperse red 13, which allowed for visually studying the degradation of the hydrogels through the hydrolysis of the ester bonds of the dendritic component. The maximum swelling ratio of the gels was recorded within 4-8 h and the swelling ratios increased with higher molecular weight of the polyethylene glycol crosslinker. The gel formed with 10 kDa polyethylene glycol crosslinker showed the highest swelling ratio of 40 and good mechanical properties, with a storage modulus of 8 kPa. In addition, the hydrogels exhibited good biocompatibility towards both human fibroblasts and mouse monocytes, while showing strong antibacterial activity against both gram-positive and gram-negative bacteria.

Iminopyridine-decorated carbosilane metallodendrimers have recently emerged as a promising strategy in the treatment of cancer diseases. Their unique features such as the nanometric size, the multivalent nature and the structural perfection offer an extraordinary platform to explore structure-to-property relationships. Herein, we showcase the outstanding impact on the antitumor activity of a parameter not explored before: the iminopyridine substituents in meta position. New Cu(II) carbosilane metallodendrimers, bearing methyl or methoxy substituents in the pyridine ring, were synthesized and thoroughly characterized. Electron Paramagnetic Resonance (EPR) was exploited to unveil the properties of the metallodendrimers. This study confirmed the presence of different coordination modes of the Cu(II) ion (Cu-N 2 O 2 , Cu-N 4 and Cu-O 4 ), whose ratios were determined by the structural features of the dendritic molecules. These metallodendrimers exhibited IC 50 values in the low micromolar range (<6 μM) in tumor cell lines such as HeLa and MCF-7. The subsequent in vitro assays on both healthy (PBMC) and tumor (U937) myeloid cells revealed two key facts which improved the cytotoxicity and selectivity of the metallodrug: First, maximizing the Cu-N 2 O 2 coordination mode; second, adequately selecting the pair ring-substituent/metal-counterion. The most promising candidates, G 1 (-CH 3 )Cl (8) and G 1 (-OCH 3 )NO 3 (17), exhibited a substantial increase in the antitumor activity in U937 tumor cells, compared to the non-substituted counterparts, probably through two different ROS-production pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

SARS‑CoV‑2 is a newly discovered member of the betacoronaviruses and the etiological agent of the disease COVID‑19. SARS‑CoV‑2 is responsible for the worldwide pandemic which has been taking place in 2020, and is causing a markedly higher number of infections and deaths compared to previous coronaviruses, such as SARS‑CoV or MERS‑CoV. Based on updated scientific literature, the present review compiles the most relevant knowledge of SARS‑CoV‑2, COVID‑19 and the clinical and typical responses that patients have exhibited against this virus, discussing current and future therapies, and proposing strategies with which to combat the disease and prevent a further global threat. The aggressiveness of SARS‑CoV‑2 arises from its capacity to infect, and spread easily and rapidly through its tight interaction with the human angiotensin‑converting enzyme 2 (ACE‑2) receptor. While not all patients respond in a similar manner and may even be asymptomatic, a wide range of manifestations associated with COVID‑19 have been described, particularly in vulnerable population groups, such as the elderly or individuals with other underlying conditions. The proper function of the immune system plays a key role in an individual's favorable response to SARS‑CoV‑2 infection. A hyperactivated response, on the contrary, could account for the more severe cases of COVID‑19, and this may finally lead to respiratory insufficiency and other complications, such as thrombotic or thromboembolic events. The development of novel therapies and vaccines designed to control and regulate a proper immune system response will be key to clinical management, prevention measures and effective population screening to attenuate the transmission of this novel RNA virus.

Heterofunctional dendrimers with internal and external representations of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over the structure, molecular weight, number, and location of different cargos across the whole dendritic skeleton. Consequently, these dendrimers with multipurpose characters are the pinnacle of precision polymers and thereof are highly attractive to the scientific community as they can find use in a great number of cutting-edge applications, especially as discrete unimolecular carriers for therapeutic exploitation. Unfortunately, most established dendrimer families display external functionalities but lack internal scaffolding ability, which leads to inherent limitations to their full potential use as precision carriers. Consequently, here, we embark on a novel synthetic strategy facilitating the introduction of internal functionalization of established dendrimers. As a proof of concept, a new class of internally and externally functionalized multipurpose dendrimers based on the established 2,2-bis(methylol)propionic acid (bis-MPA) was successfully obtained by the elegant and simple design of AB 2 C monomers, amalgamated from two traditional AB 2 monomers. Utilizing fluoride-promoted esterification (FPE), straightforward layer-by-layer divergent growth up to the fourth generation was successful in less than one day of reaction time, with a molecular weight of 15 kDa, and displaying 93 reactive groups divided by 45 internal and 48 external functionalities. The feasibility of postfunctionalization through click reactions is demonstrated, where the fast and effective attachment of drugs, dyes, and PEG chains is achieved, as well as cross-linking into multifunctional hydrogels. The simplicity and versatility of the presented strategy can easily be transferred to generate a myriad of functional materials such as polymers, surfaces, nanoparticles, or biomolecules.

Background: Chronic venous disease (CVD) is a prevalent lower limb venous pathology that especially affects women, who also show an increased risk of this disease during pregnancy. Studies have shown significant structural changes in the placentas of women with CVD and several markers of tissue damage have been also described. Patients and Methods: To try to understand the different placental pathologies, research efforts have focused on examining metabolomic profiles as indicators of the repercussions of these vascular disorders. This study examines changes produced in the metabolomic profiles of chorionic villi in the placentas of women with CVD. In a study population of 12 pregnant women, 6 with and 6 without CVD, we compared through mass spectroscopy coupled to ultra-high performance liquid chromatography (UHPLC-MS), 240 metabolites in chorionic villus samples. Results: This study is the first to detect in the placental villi of pregnant women with CVD, modifications in lysophosphatidylcholines and amino acids along with diminished levels of other lipids such as triglycerides, sphingomyelins, and non-esterified omega 9 fatty acids, suggesting a role of these abnormalities in the pathogenesis of CVD. Conclusions: Our findings are a starting point for future studies designed to examine the impacts of CVD on maternal and fetal well-being., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Infectious diseases are one of the main global public health risks, predominantly caused by viruses, bacteria, fungi, and parasites. The control of infections is founded on three main pillars: prevention, treatment, and diagnosis. However, the appearance of microbial resistance has challenged traditional strategies and demands new approaches. Dendrimers are a type of polymeric nanoparticles whose nanometric size, multivalency, biocompatibility, and structural perfection offer boundless possibilities in multiple biomedical applications. This review provides the reader a general overview about the uses of dendrimers and dendritic materials in the treatment, prevention, and diagnosis of highly prevalent infectious diseases, and their advantages compared to traditional approaches. Examples of dendrimers as antimicrobial agents per se, as nanocarriers of antimicrobial drugs, as well as their uses in gene transfection, in vaccines or as contrast agents in imaging assays are presented. Despite the need to address some challenges in order to be used in the clinic, dendritic materials appear as an innovative tool with a brilliant future ahead in the clinical management of infectious diseases and many other health issues.

In searching for efficient and selective antitumour drugs, a new family of carbosilane metallodendrimers functionalized with [Ru(η 5 -C 5 H 5 )(PTA)Cl] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1] decane) is reported. Experiments of the biophysical characterization showed an ability to interact with biological membranes, as well as with proteins (e.g. human serum albumin) without affecting their usual biological activity. These metallodendrimers possessed potent and selective anticancer activity in vitro in a panel of tumour cell lines. Importantly, the first generation metallodendrimer, bearing 4 Ru(II) complexes, was remarkably active towards resistant prostate cancer cells, inhibiting both cell proliferation and metastasis to bone tissues. Such promising antitumour activity can be further improved when given with docetaxel, with in vitro cytotoxicity being in the nanomolar range. Furthermore, its intravenous administration to an advanced prostate cancer mice model inhibited tumour growth up to 25% and 45% when given 10 mg/kg/week and 7.5 mg/kg/4-5 days, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Copper(II) carbosilane metallodendrimers are promising nanosized anticancer metallodrugs. The precise control on their design enables an accurate structure-to-activity study. We hypothesized that different structural features, such as the dendrimer generation and metal counterion, modulate the interaction with tumor cells, and subsequently, the effectivity and selectivity of the therapy. A computer-aided analysis of the electron paramagnetic resonance (EPR) spectra allowed us to obtain dynamical and structural details on the interactions over time between the dendrimers and the cells, the myeloid U937 tumor cells and peripheral blood mononuclear cells (PBMC). The intracellular fate of the metallodendrimers was studied through a complete in vitro evaluation, including cytotoxicity, cytostaticity, and sublethal effects regarding mitochondria function, lysosomal compartments, and autophagic organelle involvement. EPR results confirmed a higher membrane stabilization for chloride dendrimers and low generation complexes, which ultimately influence the metallodrug uptake and intracellular fate. The in vitro evaluation revealed that Cu(II) metallodendrimers are cytostatic and moderate cytotoxic agents for U937 tumor cells, inducing death processes through the mitochondria-lysosome axis as well as autophagic vacuole formation, while barely affecting healthy monocytes. The study provided valuable insight into the mechanism of action of these nanosized metallodrugs and relevant structural parameters affecting the activity.

Chemoselective reactions are a highly desirable approach to generate well-defined functional macromolecules. Their extraordinary efficiency and selectivity enable the development of flawless structures, such as dendrimers, with unprecedented structure-to-property capacity but with typically tedious synthetic protocols. Here we demonstrate the potency of chemoselective reactions to accomplish sequence-controlled heterolayered dendrimers. An accurate accelerated design of bis-MPA monomers with orthogonally complementary moieties and a wisely selected chemical toolbox generated highly complex monodisperse dendrimers through simplified protocols. The versatility of the strategy was proved by obtaining different dendritic families with different properties after altering the order of addition of the monomers. Moreover, we evaluated the feasibility of the one-pot approach toward these heterolayered dendrimers as proof-of-concept.

Dendrimers exhibit unique interactions with cell membranes, arising from their nanometric size and high surface area. To a great extent, these interactions define their biological activity and can be reported in situ by spin-labelling techniques. Schiff-base carbosilane ruthenium (II) metallodendrimers are promising antitumor agents with a mechanism of action yet to explore. In order to study their in situ interactions with model cell membranes occurring at a molecular level, namely cetyltrimethylammonium bromide micelles (CTAB) and lecithin liposomes (LEC), electron paramagnetic resonance (EPR) was selected. Both a spin probe, 4-( N , N -dimethyl- N -dodecyl)ammonium-2,2,6,6-tetramethylpiperidine-1-oxyl bromide (CAT12), able to enter the model membranes, and a spin label, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) covalently attached at newly synthesized heterofunctional dendrimers, were used to provide complementary information on the dendrimer-membrane interactions. The computer-aided EPR analysis demonstrated a good agreement between the results obtained for the spin probe and spin label experiments. Both points of view suggested the partial insertion of the dendrimer surface groups into the surfactant aggregates, mainly CTAB micelles, and the occurrence of both polar and hydrophobic interactions, while dendrimer-LEC interactions involved more polar interactions between surface groups. We found out that subtle changes in the dendrimer structure greatly modified their interacting abilities and, subsequently, their anticancer activity.

Antibiotic resistance is currently one of the main threats to public health security. Biofilm formation is a resistance mechanism that is responsible for most human bacterial infections and requires new and effective therapeutic approaches, such as those provided by nanotechnology. In this work, the antibacterial effect of carbosilane metallodendrimers with different metals (copper(II) and ruthenium(II)), ligands (chloride and nitrate) and generations (generation 0, 1 and 2) has been studied using planktonic Gram-positive ( Staphylococcus aureus ) and Gram-negative ( Escherichia coli ) bacteria. Furthermore, the ability of the metallodendrimers to avoid the formation of S. aureus biofilms was also evaluated. The results showed a promising biocide activity in both types of planktonic bacteria, especially for first-generation dendrimers, which arises from the metal complexation to the dendrimer. Cu(II) metallodendrimers require lower concentration than Ru(II) counterpart to inhibit the production of S. aureus biofilms, but none produce hemolysis at the inhibitory concentrations and can be safely used as antibacterial agents. In particular, the first-generation Cu(II) metallodendrimer with nitrate ligands displayed the most promising properties to continue with further studies in both planktonic cells and biofilms.

Current cancer therapies present serious drawbacks including severe side-effects and development of drug resistance. Strategies based on nanosized metallodrugs combine the structural diversity and non-classical modes of action of metal complexes with the selectivity arising from the unique interaction of nanoparticles with biological membranes. A new family of water-soluble copper(ii) carbosilane metallodendrimers was synthesized and characterized as a nanotechnological alternative to current therapies. The interactions occurring over time between the dendrimers, at different generations (G 0 to G 2 ) and with different Cu(ii) counter-ions (nitrate vs. chloride), and cell-membrane models (cethyl-trimethylammonium bromide (CTAB) micelles and lecithin liposomes) were investigated using a computer-aided analysis of the electron paramagnetic resonance (EPR) spectra. The EPR analysis provided structural and dynamical information on the systems indicating that the increase in generation and the change of the Cu(ii) contra-ion - from nitrate to chloride - produce an increased relative amount and strength of interaction of the dendrimer with the model membranes. Interestingly, the stabilization effect produced a lower toxicity towards cancer cells. The cytotoxic effect of Cu(ii) metallodendrimers was verified by an in vitro screening in a selection of tumor cell lines, revealing the impact of multivalency on the effectivity and selectivity of the metallodrugs. As a proof-of-concept, first-generation dendrimer G 1 -Cu(ONO 2 ) 2 was selected for in-depth in vitro and in vivo antitumor evaluation towards resistant prostate cancer. The Cu(ii)-metallodendrimers produced a significant tumor size reduction with no signs of toxicity during the experiment, confirming their promising potential as anticancer metallodrugs.

Newly synthesized carbosilane copper dendrimers (CCD) with chloride and nitrate surface groups seem to be good candidates to be used as gene and drug carriers in anti-cancer therapy, due to their properties such as size and surface charge. Copper attached to the nanoparticles is an important element of many biological processes and recently their anti-cancer properties have been widely examined. Zeta size and potential, transmission electron microscopy (TEM), circular dichroism (CD), analysis of haemolytic activity, and fluorescence anisotropy techniques were used to characterize copper dendrimers. Additionally, their cytotoxic properties toward normal (PBMC) and cancer (1301; HL-60) cells were examined. All tested dendrimers were more cytotoxic against cancer cells in comparison with normal cells.

In recent years innovative nanostructures are attracting increasing interest and, among them, dendrimers have shown several fields of application. Dendrimers can be designed and modified in plentiful ways giving rise to hundreds of different molecules with specific characteristics and functionalities. Biomedicine is probably the field where these molecules find extraordinary applicability, and this is probably due to their multi-valency and to the fact that several other chemicals can be coupled to them to obtain desired compounds. In this review we will describe the different production strategies and the tools and technologies for the study of their characteristics. Finally, we provide a panoramic overview of their applications to meet biomedical needs, especially their use as novel antimicrobials., Competing Interests: The authors declare no conflict of interest.

The development of novel strategies to prevent HIV-1 infection is of outstanding relevance. Metal complexes of Cu(2+), Ni(2+), Co(2+) and Zn(2+) derived from sulfonated and carboxylated poly(propylene imine) dendrimers with ethylenediamine core were evaluated as tunable antiviral agents against HIV-1. After demonstrating their biocompatibility, specific trends in the antiviral properties were found, related to both the dendritic scaffold (peripheral group, generation) and the bound metal ions (sort, amount). In HEC-1A and VK-2 cell lines, as model of the first barrier against HIV-1 infection, a high preventive inhibitory action was found, which also avoided virus internalization inside cells and inhibited both CCR5 and CXCR4 HIV-1 strains. In peripheral blood mononuclear cells (PBMC), as model of the second barrier, a dual preventive and therapeutic behavior was observed. A rational design of such metallodendrimers opens new avenues for the production of versatile and efficient treatments against HIV-1 infection., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Based on the growing demand for facile and sustainable synthetic methods to structurally perfect polymers, we herein describe a significant improvement of esterification reactions capitalizing on 1,1'-carbonyldiimidazole (CDI). Cesium fluoride was shown to be an essential catalyst for these reactions to reach completion. This approach was successfully applied to the synthesis of structurally flawless and highly functional polyester dendrimers employing traditional and accelerated growth strategies. A sixth generation bis-MPA dendrimer with a molecular weight of 22.080 Da and 192 peripheral hydroxy groups was isolated in less than one day of total reaction time. Large quantities of dendrimers were obtained in high yields (>90%) using simple purification steps under sustainable conditions. The fluoride-promoted esterification (FPE) via imidazolide-activated compounds is wide in scope and constitutes a potentially new approach toward functional polymers and other materials., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development of carbon-monoxide-releasing molecules (CORMs) as pharmaceutical agents represents an attractive and safer alternative to administration of gaseous CO. Most CORMs developed to date are transition-metal carbonyl complexes. Although such CORMs have showed promising results in the treatment of a number of animal models of disease, they still lack the necessary attributes for clinical development. Described in this Minireview are the methods used for CORM selection, to date, and how new insights into the reactivity of metal-carbonyl complexes in vivo, together with advances in methods for live-cell CO detection, are driving the design and synthesis of new CORMs, CORMs that will enable controlled CO release in vivo in a spatial and temporal manner without affecting oxygen transport by hemoglobin., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein we describe the synthesis and characterization of new sulfonated and carboxylated poly(propyleneimino) (PPI) dendrimers with the ethylenediamino (EDA) core, at generations 1, 2 and 3. By means of UV-Vis and EPR spectroscopy, using Cu(2+) as a probe, we concluded that these dendrimers show a specific pattern in the coordination of metal ions. In agreement with the UV-Vis studies, EPR spectra of carboxylated compounds are constituted by 3 different signals which appear and then disappear with increasing copper concentration, corresponding to the saturation of different copper complexation sites. At the lowest copper concentration up to a 1:1 molar ratio between Cu(II) and the dendrimer, the spectrum is characteristic of a CuN2O2 coordination at the core of the dendrimer. The spectrum appearing at higher Cu(II) concentrations indicates a peripheral location of the ions coordinating one nitrogen and 3 oxygen atoms in a square planar geometry in restricted mobility conditions. For the highest concentrations tested, copper ions are confined at the external dendrimer surface with CuO4 coordination. For sulfonate systems, the EPR results are in line with a weaker interaction of Cu(II) with the nitrogen sites and a stronger interaction with the oxygen (SO3(-)) groups with respect to the interactions measured by EPR for carboxylate systems.

We describe here the synthesis and characterization of new sulfonated and carboxylated-containing N-donor ligands [Na(4)(edts)]·4H(2)O (2), [Na(2)(dmeddp)]·2H(2)O (3) and [Na(4)(edtp)]·H(2)O (4) (edts = ethylene-diamine- N,N,N',N'-tetraethylenesulfonate ion; dmeddp = dimethyl-ethylene-diamine-N,N,N',N'-tetra-3-propionate ion; edtp = ethylene-diamine-N,N,N',N'-tetra-3-propionate ion) and their corresponding metal (Ni, Co, Cu and Zn) complexes. Mainly, UV-Vis and a computer aided analysis of the EPR spectra provided information on the geometry and structure of the complexes in solution. Some of the metal complexes inhibit HIV replication when treating both pre- and post-infected PBMC cells, and hustle the inhibitory effect compared to the metal salts alone.

New amine-terminated carbosilane dendrimers have been prepared by a Huisgen cycloaddition ("click chemistry" reaction) of azide-terminated carbosilane dendrimers with two different propargyl amines. The corresponding cationic derivatives with peripheral ammonium groups were obtained by subsequent addition of MeI. Quaternized dendrimers are soluble and stable in water or other protic solvents for long time periods, and have been studied as nonviral vectors for the transfection of DNA to cancer cells. In this study DNA-dendrimeric nanoparticles (dendriplexes) formulated with two different families of cationic carbosilane dendrimers (family 1 (G1, G2 and G3) and family 2 (G1, G2)) were characterized and evaluated for their ability to transfect cells in vitro and in vivo. Dendriplex derived from second generation dendrimer of family 1 (F1G2 5/1 (+/-)) increased the efficiency of plasmid-mediated gene transfer in HepG2 cells as compared to naked DNA and the commercial control dendrimer. Also, intravenously administered dendriplex F1G3 20/1 (+/-) is superior in terms of gene transfer efficiency in vivo.