Raquel F. M. Frade

5-Hydroxymethylfurfural (HMF) as a building block platform: Biological properties, synthesis and synthetic applications

The biorefinery is an important approach for the current needs of energy and chemical building blocks for a diverse range of applications, that gradually may replace current dependence on fossil-fuel resources. Among other primary renewable building blocks, 5-hydroxymethylfurfural (HMF) is considered an important intermediate due to its rich chemistry and potential availability from carbohydrates such as fructose, glucose, sucrose, cellulose and inulin. In recent years, considerable efforts have been made on the transformation of carbohydrates into HMF. In this critical review we provide an overview of the effects of HMF on microorganisms and humans, HMF production and functional group transformations of HMF to relevant target molecules by taking advantage of the primary hydroxyl, aldehyde and furan functionalities.

Impact of ionic liquids in environment and humans: An overview

Ionic liquids enclose a large number of molecular structures consisting of a cation and an anion. Their physical state and their chemical properties can be tuned by different combination of the ions and a large number of ionic liquids have already been reported. Toxicity of ionic liquids is a subject of great importance concerning their likely use as greener solvents and new materials for a broad number of potential applications. This review provides relevant toxicological data published so far about this topic and includes a large range of ionic liquids based on different cations (imidazolium, pyridinium, pyrrolidinium, quaternary ammonium, quaternary phosphonium and guanidinium) and anions (halogens-Br, Cl, bis (trifluoromethyl)sulfonylamide, tetrafluoroborate, hexafluorophosphate, dicyanamide, acesulfame and saccharin, amongst others). In general, toxicity of ionic liquids depends on both ions and the effect of the cation alkyl chain length is very pronounced although the type of anion also exerts impact on the overall toxicity.

Effect of ionic liquids on human colon carcinoma HT-29 and CaCo-2 cell lines

The toxicity of ionic liquids, involving different classes of cations and different types of anions, was evaluated by a colorimetric assay with 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) in two colon carcinoma HT-29 and CaCo-2 cell lines. Confluent CaCo-2 cells can undergo spontaneously an enterocytic differentiation and represent a good in vitro model of normal human intestinal epithelium. Ionic liquids are highly promising due to their low vapour pressures, however, toxicity evaluation of these ionic liquids is of great importance to assess the risk of these ionic liquids to humans and the environment.

Toxicological evaluation on human colon carcinoma cell line (CaCo-2) of ionic liquids based on imidazolium, guanidinium, ammonium, phosphonium, pyridinium and pyrrolidinium cations

Toxicological evaluation of a new group of ionic liquids was performed on human colon cancerous cells—CaCo-2. They belong to different classes of cations: imidazolium (IM), dimethyl-guanidinium (dmg) and tetramethyl-guanidinium (tmg), methyl-pyrrolidinium (MPyr), 2-methyl-1-ethyl-pyridinium (2-MEPy), quaternary ammonium (benzyltriethyl-ammonium–BzTEA; phenyltrimethyl-ammonium–PhTMA; tri-n-octyl-methylammonium-Aliquat) and tri-n-hexyl-tetra-n-decylphosphonium (P6,6,6,14). The new results were compared with data obtained in previous reported studies performed in our lab, and we clearly saw that toxicity can vary significantly with the type of anion. Dicyanoamide-[DCA] and bis(trifluoromethanesulfonyl)amide-[NTf2] were seen to visibly change the impact of some cations. Some were considerably less harmful for CaCo-2 monolayer when the anion was [DCA] or [NTf2], while others induced an abnormal increase of cellular metabolism when [NTf2] was present and therefore, they were considered toxic. However, some cations induced similar responses in the presence of a broad number of anions as (1-butyl-3-methylimidazolium)-[C4MIM] (with the exception of [FeCl4]), (1-(2-hydroxyethyl)-3-methylimidazolium)-[C2OHMIM] and [C4MPyr] and did not cause toxicity. Consequently, they are considered promising cations for building human friendlier solvents. But, a reasonable number of other combinations involving different classes of cations were also seen to not significantly affect viability of the CaCo-2 monolayer.

Isolation, Chemical, and Biotransformation Routes of Labdane-type Diterpenes

1. Introduction and Scope 44182. Isolation and Chemical Manipulation 44192.1. Sclareol 44192.2. Sclareolide 44262.3. Labdanolic Acid 44312.4. Abietic Acid 44342.5. Larixol 44352.6. Ozic Acid 44383. Biotransformation 44383.1. Sclareol 44383.2. Sclareolide 44393.3. Stemodin 44403.4. Stemodinone 44413.5. Stemarin 44413.6. Ambrox 44423.7. Manoyl Oxide Derivatives 44433.8. Isocupresic Acid 44443.9. Epicandicandiol and Candicandiol 44453.10. Cedrol 44454. Conclusions and Future Prospects 4447Author Information 4448Biographies 4449Acknowledgment 4449References 4449

Toxicological evaluation of magnetic ionic liquids in human cell lines

Magnetic ionic liquids (MILs) are new solvents with an interesting broad of applications however their toxicity is still an open issue. In this paper we report the toxicity of [C(8)MIM] and [Choline-C(n)] based magnetic ionic liquids assessed in two human cell lines: normal skin fibroblasts (CRL-1502) and colorectal adenocarcinoma cells (CaCo-2), acquiring this last characteristics of human enterocytes after differentiation. The results showed that [CoCl(4)] and [MnCl(4)] are more prone to generate cytotoxicity.

Development of novel sophorolipids with improved cytotoxic activity toward MDA-MB-231 breast cancer cells.

Sophorolipids (SLs) are glycolipid biosurfactants, produced as a mixture of several compounds by some nonpathogenic yeast. In the current study, separation of individual SLs from mixtures with further evaluation of their surface properties and biologic activity on MDA‐MB‐321 breast cancer cell line were investigated. SLs were biosynthesized by Starmerella bombicola in a culture media supplemented with borage oil. A reverse‐phase flash chromatography method with an automated system coupled with a prepacked cartridge was used to separate and purify the main SLs. Compositional analysis of SLs was performed by high‐performance liquid chromatography with electrospray ionization mass spectrometry and tandem mass spectrometry. The following diacetylated lactonic SLs were isolated and purified: C18:0, C18:1, C18:2, and C18:3. The critical micelle concentration (CMC) and surface tension at CMC (γCMC) of the purified SLs showed an increase with the number of double bonds. High cytotoxic effect against MDA‐MB‐231 cells was observed with C18:0 and C18:1 lactonic SLs. The cytotoxic effects of C18:3 lactonic SL on cancerous cells were for the first time studied. This cytotoxic effect was considerably higher than the promoted by acidic SLs; however, it induced a lower effect than the previously mentioned SLs, C18:0 and C18:1. To our knowledge, for the first time, C18:1 lactonic SL, in selected concentrations, proved to be able to inhibit MDA‐MB‐231 cell migration without compromising cell viability and to increase intracellular reactive oxygen species. Copyright

Reversible lysine modification on proteins by using functionalized boronic acids.

Iminoboronates have been utilized to successfully install azide and alkyne bioorthogonal functions on proteins, which may then be further reacted with their bioorthogonal counterparts. These constructs were also used to add polyethylene glycol (PEG) to insulin, a modification which has been shown to be reversible in the presence of fructose. Finally, iminoboronates were used to assemble a folic acid/paclitaxel small-molecule/drug conjugate in situ with an IC50  value of 20.7 nM against NCI-H460 cancer cells and negligible cytotoxicity against the CRL-1502 noncancer cells.

Iso-seco-tanapartholides: Isolation, Synthesis and Biological Evaluation

The isolation, identification and total synthesis of two plant-derived inhibitors of the NF-κB signaling pathway from the iso-seco-tanapartholide family of natural products is described. A key step in the efficient reaction sequence is a late-stage oxidative cleavage reaction that was carried out in the absence of protecting groups to give the natural products directly. A detailed comparison of the synthetic material with samples of the natural products proved informative. Biological studies on synthetic material confirmed that these compounds act late in the NF-κB signaling pathway. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

New dirhodium complex with activity towards colorectal cancer.

A novel dirhodium complex (Rh(2)(L-PheAla)(2)(OAc)(2) is reported with strong activity towards human colon adenocarcinoma cells. Its effect was not accompanied by generation of reactive oxygen species (ROS) neither by activation of caspase-3.