Carboxyl End Research Articles

Biodegradation Behavior of Degradable Mulch with Poly (Butylene Adipate-co-Terephthalate) (PBAT) and Poly (Butylene Succinate) (PBS) in Simulation Marine Environment.

Poly (butylene adipate-co-terephthalate) (PBAT) and poly (butylene succinate) (PBS) are polyester materials with excellent biodegradability under soil and compost conditions. However, the research on their degradation process in the marine environment is scarce. In this study, a more realistic simulation marine environment with sediment and marine organisms was developed, followed by investigation of the biodegradation behavior of PBAT and PBS mulch in it. The effect of aromatic structure, carboxyl end group content, molecular weight, and inorganic fillers on the degeneration of mulch was characterized by the changes in appearance, chemical structure, thermal properties, and crystallinity via Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, gel permeation chromatography, element analysis, and X-ray photoelectron spectroscopy. The molecular weight of polyester blends decreased, while the content of the C-O bond in the composites increased, indicating that the samples indeed degraded. The degradation rate was measured with the CO2 release amount. The aliphatic polyester structure, lower molecular weight, higher carboxyl end group content, and the involvement of inorganic fillers facilitate the disintegration of polyester in the marine environment, which provides an effective method to construct materials with controllable biodegradable performance.

Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells.

Folic acid-conjugated nanophotosensitizers composed of folic acid (FA), poly(ethylene glycol) (PEG) and chlorin e6 (Ce6) tetramer were synthesized using diselenide linkages for reactive oxygen species (ROS)- and folate receptor-specific delivery of photosensitizers. Ce6 was conjugated with 3-[3-(2-carboxyethoxy)-2,2-bis(2-carboxyethoxymethyl)propoxy]propanoic acid (tetra acid, or TA) to make Ce6 tetramer via selenocystamine linkages (TA-sese-Ce6 conjugates). In the carboxylic acid end group of the TA-sese-Ce6 conjugates, FA-PEG was attached again using selenocystamine linkages to make FA-PEG/TA-sese-Ce6 conjugates (abbreviated as FAPEGtaCe6 conjugates). Nanophotosensitizers were fabricated by a dialysis procedure. In the morphological observations, they showed spherical shapes with small diameters of less than 200 nm. Stability of the aqueous FAPEGtaCe6 nanophotosensitizer solution was maintained (i.e., their particle sizes were not significantly changed until 7 days later). When H2O2 was added to the nanophotosensitizer solution, the particle size distribution was changed from a monomodal pattern to a multimodal pattern. In addition, the fluorescence intensity and Ce6 release rate from the nanophotosensitizers were also increased by the addition of H2O2. These results indicated that the nanophotosensitizers had ROS-sensitive properties. In an in vitro cell culture study, an FAPEGtaCe6 nanophotosensitizer treatment against cancer cells increased the Ce6 uptake ratio, ROS generation and light-irradiated cytotoxicity (phototoxicity) compared with Ce6 alone against various cancer cells. When the folic acid was pretreated to block the folate receptors of the Y79 cells and KB cells (folate receptor-overexpressing cells), the intracellular Ce6 uptake, ROS generation and thereby phototoxicity were decreased, while the MCF-7 cells did not significantly respond to blocking of the folate receptors. These results indicated that they could be delivered by a folate receptor-mediated pathway. Furthermore, an in vivo pulmonary metastasis model using Y79 cells showed folate receptor-specific delivery of FAPEGtaCe6 nanophotosensitizers. When folic acid was pre-administered, the fluorescence intensity of the lungs was significantly decreased, indicating that the FAPEGtaCe6 nanophotosensitizers had folate receptor specificity in vitro and in vivo. We suggest that FAPEGtaCe6 nanophotosensitizers are promising candidates for a targeted photodynamic therapy (PDT) approach against cancer cells.

The utilities of pyrazolines encouraged synthesis of a new pyrazoline derivative via ring closure of chalcone, for optimistic neurodegenerative applications

Pyrazolines and their derivatives have been extensively studied as coordinated ligands of high potential applications in diverse chemical and biological systems. This work explores some methods of synthesis of pyrazolines, such as the preparation of pyrazole derivatives via chalcones. It also demonstrates that 2-pyrazoline complexes were biologically active and have had a range of clinical applications. Palladium (II) complex of pyrazole was active as antitumor when tested against murine mammary adenocarcinoma (LM3). Copper (II) and Cobalt (II) complex are biologically active in the living system as biomolecules or co factors. Based on these information, we tried here to synthesis a new 2-pyrazoline from (E)-3-(4-bromophenyl)-1-(pyridin-2-yl)prop-2-en-1-one. The newly synthesized pyrazoline was characterized using mass spectroscopy, nucleic magnetic resonance spectroscopy NMR and Fourier transform infrared spectroscopy FTIR. The characterization results showed that 2-pyrazoline has successfully synthesized. The microanalyses (C.H.N.S), GC-MS, H and 13C NMR and FT-IR spectra confirmed the formation of 2-pyrazoline ring with substitution at N1,C-3 and C-5 and the spin-spin coupling constants (J) for the multiple peaks at H NMR spectra pointed to the de shielded aromatic protons in α and β protons of the prepared chalcone. Interestingly, some new family of pyrazoles that have isosteres of Zonisamide have previously showed activity toward treating neuroglial disorders such as epilepsy and autism. Thus, our synthesized pyrazole could have the potency to moderate some neurodegenerative disorders. It could negatively interact with some neurotransmitters through hydrogen bonding and electrostatic interactions with the amino and carboxylic ends of the functional ends of the neurotransmitters. This promising trend by the promising candidate 2- pyrazoline should have further investigations.

Fabrication of highly efficient phenylphosphorylated chitosan bio-based flame retardants for flammable PLA biomaterial

Modified chitosan (CS)-based flame retardants exhibit promising prospects owing to their sustainability, biodegradability, and good charring properties. A series of novel modified-CS bio-based flame retardants (phenylphosphorylated CS (PhPCS) and phenylphosphoramidated CS (PhPNCS)) were prepared by the phosphorylation and phosphoramidation reactions of CS with phenylphosphoryl dichloride and tetraethylenepentamine, respectively. Bio-based PhPCS and PhPNCS exhibited excellent flame retardancy efficiency for poly(lactic acid) (PLA). The limited oxygen index (LOI) values of the PLA/3 wt% PhPCS and PLA/3 wt% PhPNCS biocomposites increased to 29% and 27%, respectively, and they both achieved a V-0 rating during the UL-94 vertical combustion test. However, the mechanical properties of the PLA/PhPCS biocomposites decreased with increasing PhPCS content. The mechanical strengths of the PLA/PhPNCS biocomposites were better than those of the PLA/PhPCS biocomposites owing to the reactive compatibilization of the interface between the amino and carboxyl end groups of the PhPNCS nanoparticles and PLA matrix, respectively.

Hydrolytic Depolymerization of Polyethylene Terephthalate by Reactive Extrusion

Abstract Continuous hydrolytic depolymerization of polyethylene terephthalate (PET) resin at high temperature and pressure was carried out in a co-rotating twin screw extruder. In this novel process, hydrolysis is achieved by injection of saturated steam at high pressure. Optimum conditions occur at relatively low screw speeds and water/PET ratios. Hydrolysis extent was measured using carboxyl end group titration, and by determination of molecular weights using NMR and GPC analysis. Low molecular weight products are obtained at low residence times in the extruder, suggesting high depolymerization rates. This is supported by the results of a simple kinetic model.

Insight into Chemical Recycling of Flexible Polyurethane Foams by Acidolysis.

Acidolysis is emerging as a promising method for recycling polyurethane foam (PUF) waste. Here, we present highly efficient acidolysis of PUFs with adipic acid (AA) by heating the reaction mixtures with microwaves. The influence of experimental conditions, such as reaction temperature, time, and amount of the degradation reagent, on the polyol functionality, molecular weight characteristics, the presence of side products, and the degree of degradation of the remaining PUF hard segments was studied by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS), nuclear magnetic resonance (NMR), size-exclusion chromatography (SEC) coupled to a multidetection system, and Fourier transform infrared (FT-IR) spectroscopy. The purified recycled polyols were used for the synthesis of flexible PUFs. The morphology and mechanical properties of the PUFs show that the degree of functionalization of the polyol by the carboxylic end groups, which is higher for larger amounts of AA used to degrade the PUFs, significantly affects the quality and performance of the flexible PUFs from the recycled polyols.

Electron Transport Mechanisms in Polyethylene Terephthalate Membranes

This paper describes carrier transport mechanisms in polyethylene terephthalate (PET) films and porous PET-based membranes (PMs) obtained by irradiating pristine PET film with swift heavy ions, with subsequent chemical etching in an alkali (NaOH) solution. The obtained PMs had through nanochannels (pores) with an average diameter of 720-750 nm. We observed that in the temperature range 240-300 K, the current-voltage characteristics I(V) of the initial Cu|PET|Cu structure obeyed the improved Mott--Gurney law, which is based on the Mark--Helfrich model for a space-charge-limited current (SCLC) mechanism for electron transport. It was found for the first time that creation of nanochannels in PMs resulted in a significant increase in the electric current density (by about three orders of magnitude) while maintaining the SCLC mechanism. The enhanced current density is explained by the formation of a highly conductive layer along the inner surface of the walls of the nanochannel that are covered with carboxyl end groups, which are created by alkaline hydrolysis. According to the model, the surface states formed by these groups enable the drift of additional electrons injected from the copper electrodes under the action of the bias voltage. Keywords: polyethylene terephthalate, electron transport, space-charge-limited current mechanism, Mark--Helfrich injection model.

Overcoming tumor heterogeneity by ex vivo arming of T cells using multiple bispecific antibodies

BackgroundTumorous heterogeneity is a hallmark of tumor evolution and cancer progression, being a longstanding challenge to targeted immunotherapy. Ex vivo armed T cells (EATs) using IgG-(L)-scFv bispecific antibodies (BsAbs) are...

5-FU@DHA-UIO-66-NH2 potentiates chemotherapy sensitivity of breast cancer cells through a microRNA let-7a-dependent mechanism.

BackgroundDrug delivery systems with magnetization facilitate the accumulation of drug at the target site. This study aimed to explore the mechanism by which docosahexaenoic acid (DHA)-modified porous metal-organic framework (MOF) UIO-66-NH2 loads chemotherapeutic drug 5-fluorouracil (5-FU) and reduces the chemotherapy resistance of breast cancer (BC) cells.MethodsUIO-66-NH2 was synthesized and DHA with carboxyl end was used to modify the surface of UIO-66-NH2. 5-FU was incorporated to UIO-66-NH2 or DHA-UIO-66-NH2 by a post-synthesis method. The loading and release of 5-FU by @DHA-UIO-66-NH2 was investigated with ultraviolet (UV) spectroscopy. RT-qPCR was conducted to detect the expression of let-7a in cells. The uptake of DHA-UIO-66-NH2 by MCF-7 BC cells was observed by confocal laser scanning microscope (CLSM). Cell counting kit-8 (CCK-8), flow cytometry, and live/dead cell staining were applied to investigate the effects of 5-FU@DHA-UIO-66-NH2 on BC cells, and a BC mouse model was established to explore its effects on tumorigenesis. HE staining and routine blood index analysis were applied for determination of the biological safety of 5-FU@DHA-UIO-66-NH2.Results5-FU@DHA-UIO-66-NH2 was successfully constructed and characterized. The loading amount of DHA-UIO-NH2 for 5-FU reached 30.31%. DHA-UIO-66-NH2 was effectively taken up by MCF-7 cells. Further, 5-FU@DHA-UIO-66-NH2 exhibited stronger inhibitory effects on MCF-7 cell viability in vitro as well as tumorigenesis in vivo than 5-FU and 5-FU@UIO-66-NH2. DHA up-regulated let-7a to reduce the resistance of MCF-7 cells to 5-FU. Moreover, the biosafety of 5-FU@DHA-UIO-66-NH2 was identified.Conclusions5-FU@DHA-UIO-66-NH2 increased the level of let-7a in BC cells, repressed cell viability and augmented apoptosis, and thus reduced the chemotherapy resistance of BC cells.

The proliferation and colonization of functional bacteria on amorphous polyethylene terephthalate: Key role of ultraviolet irradiation and nonionic surfactant polysorbate 80 addition

Environmental pollution with plastics including polyethylene terephthalate (PET) has become a severe global problem, especially microplastic pollution, which is acknowledged as an emerging global pollutant. Biodegradation as a feasible and promising method has been studied, while colonization as the initiating step of the degradation process has seldom been studied. Here in this paper, we explored for the first time the key role of ultraviolet (UV) irradiation and nonionic surfactant polysorbate 80 (Tween-80, 0.2% V/V) in the proliferation and colonization of three functional bacteria (Pseudomonas putida, Pseudomonas sp. and Paracoccus sp.) on amorphous PET (APET). We found that 25 days of UV irradiation can trigger photolytic degradation process (appear the stretching vibration of associating carboxyl end group and the in-plane bending vibration of -OH) and introduce oxygen-containing functional groups on the surface of APET, even though the hydrophobicity of APET was scarcely changed. With regard to Tween-80, it can be utilized by these bacteria strains as carbon source to promote the proliferation, and it can also improve the cell surface hydrophobicity to stimulate the bacterial colonization during the first ten days of the experiment. When UV-irradiation and Tween-80 were provided together, the former factor can provide the target sites for functional bacteria to colonize, and the later factor can provide more candidates waiting to colonize by stimulating proliferation. As a result, an even better proliferation and colonization result can be achieved through the synergistic effect between the two factors. To some extent, the exposure between potential degrading bacteria and substrates to be degraded can be increased, which will create conditions for degrading. Generally, this research can provide certain theoretical basis and technical guidance for the remediation of plastic-polluted soil and the ocean.

A GX2GX3G motif facilitates acyl chain sequestration by Saccharomyces cerevisiae acyl carrier protein

Saccharomyces cerevisiae acyl carrier protein (ScACP) is a component of the large fungal fatty acid synthase I (FAS I) complex. ScACP comprises two subdomains: a conserved ACP domain that shares extensive structural homology with other ACPs and a unique structural domain. Unlike the metazoan type I ACP that does not sequester the acyl chain, ScACP can partially sequester the growing acyl chain within its hydrophobic core by a mechanism that remains elusive. Our studies on the acyl-ScACP intermediates disclose a unique 188GX2GX3G195 sequence in helix II important for ACP function. Complete loss of sequestration was observed upon mutation of the three glycines in this sequence to valine (G188V/G191V/G195V), while G191V and G188V/G191V double mutants displayed a faster rate of acyl chain hydrolysis. Likewise, mutation of Thr216 to Ala altered the size of the hydrophobic cavity, resulting in loss of C12- chain sequestration. Combining NMR studies with insights from the crystal structure, we show that three glycines in helix II and a threonine in helix IV favor conformational change, which in turn generate space for acyl chain sequestration. Furthermore, we identified the primary hydrophobic cavity of ScACP, present between the carboxyl end of helix II and IV. The opening of the cavity lies between the second and third turns of helix II and loop II. Overall, the study highlights a novel role of the GX2GX3G motif in regulating acyl chain sequestration, vital for ScACP function.

Study on the effect of end group on the anti-corrosion behavior of polyether derivatives

Three polyether derivatives with different end-groups were synthesized using a green solvent-free method, which were used as ash-less multifunctional anti-corrosion lubricating additives. Friction tests confirmed their good lubrication performance. Their anti-corrosion ability was comprehensively studied by using weight loss, ASTM D665 and ASTM D130 methods. SEM-EDS, QCM and Micro-IR were used to explore the mechanism. The results suggested although polyether derivatives with both carbon–carbon double bond and carboxyl as end-groups showed the best adsorption ability, but the one only with carboxyl end-group had the best corrosion resistance.

Reduction of Nonradiative Loss in Inverted Perovskite Solar Cells by Donor-π-Acceptor Dipoles.

Inverted perovskite solar cells (IPSCs) attract growing interest because of their simple configuration, reliable stability, and compatibility with tandem applications. However, the power conversion efficiency (PCE) of IPSCs still lags behind their regular counterparts, mainly due to the more serious nonradiative loss. Here, we design three donor-π-acceptor (D-π-A) dipoles with various dipole moments to introduce extra electric fields at the interface of perovskites and electron transport materials via the binding between the carboxylate end group and under-coordinated divalent Pb. The chemical binding reduces the recombination centers, while the superposition of the built-in electric field facilitates the electron collection and the hole blocking. As a result, the nonradiative loss is diminished as the dipole moments of D-π-A dipoles increase, which contributes to a PCE of 21.4% with enhancement in both the open-circuit voltage and fill factor. The stability for an unencapsulated device is also improved due to the hydrophobic property of D-π-A dipoles.

Carboxyl functional group-assisted defects passivation strategy for efficient air-processed perovskite solar cells with excellent ambient stability

Because the perovskites materials tend to decompose in humid air and at high temperature, a controlled inert condition is usually necessary to obtain high-performance perovskite solar cells (PSCs), which is inconvenient for large-scale commercial production. Furthermore, defects/traps in the perovskite layer, as non-radiative charge recombination centers, dramatically deteriorate the device efficiency and stability. Inspired by the Lewis acid-base adduct theory, herein we report a terephthalic acid (PTA)-assisted defect passivation strategy for fabricating highly efficient and stable devices in ambient air. Density functional theory calculation confirms that electrons are located at two carboxylic acid end groups in the PTA molecule, which can serve as Lewis base to form the Lewis acid-base adduct with uncoordinated Pb2+ defects. The PTA-treatment effects promote high performance of PSCs, the champion device provides power conversion efficiency (PCE) of 18.22%, in sharp contrast to 17.41% of control sample. More importantly, unencapsulated devices retain over 80% of their original PCE after being stored for 4500 h in air (≈45% average relative humidity (RH)), exhibiting one of the best long-term stability to date. Correspondingly, PTA-treatment gives the device favorable thermal stability. Our strategy provides a simple yet effective path for passivating defects and improving performance of PSCs.

Metal-Ion-Responsive Chromogenic Probe for Rapid, On-Location Detection of Foodborne Bacterial Pathogens in Contaminated Food Items.

An amphiphilic chromogenic probe based on an oxidized di(indolyl)arylmethane backbone has been utilized for visual detection of both Cu2+ (detection limit = 8.5 ppb) and Hg2+ (detection limit = 10.2 ppb) ions via mutually independent sensing pathways. The Cu2+ ion binds to the carboxylate ends (donor site) and induces a color change from orange to yellow in the aqueous medium, while coordinating Hg2+ at the bisindolyl moiety (acceptor site) can result in the formation of a red-colored solution. Interestingly, by selecting the proper excitation channel, we can specifically excite either the monomer species or nanoaggregates. The addition of Hg2+ enhances the monomer fluorescence, while Cu2+ induces quenching. However, in both cases, metal-ion coordination triggers dissociation of a preformed self-assembled structure. Further, the in-situ-formed Cu(II) complex was utilized for rapid, on-location detection of food-borne pathogens, such as Escherichia coli (E. coli) in contaminated food items and water (detection limit = 52 CFU·mL-1). E. coli induces reduction of Cu2+ to Cu+ and transforms the yellow-colored solution into an orange-colored solution. Finally, low-cost, reusable paper strips were designed as an eco-friendly, sustainable strategy to detect bacterial pathogens.

Carboxylate-Decorated Aggregation of Octanuclear Co4Ln4 (Ln = Dy, Ho, Yb) Complexes from Ligand-Controlled Hydrolysis: Synthesis, Structures, and Magnetic Properties

One-pot reactions of an asymmetric carboxy-ether-phenol based Schiff base H2L (2-((2-hydroxy-3-methoxybenzylidene)amino)benzoic acid) with selected Ln(NO3)3·nH2O and [Co2(μ-OH2)(O2CCMe3)4(HO2CCMe3)4] (Co2-Piv) in basic MeOH medium resulted in a family of three octanuclear complexes, [CoII4LnIII4L4(μ1,3-Piv)4(μ1,1,3-Piv)2(η1-Piv)2(μ3-OH)4(MeOH)2]·mMeOH·nH2O (Ln = Dy; m = 3, n = 1 (1), Ho; m = 4, n = 0 (2), Yb; m = 3, n = 1 (3)). The coordination aggregates thus obtained were nicely sustained by four ligand anions and eight externally added carboxylate anions showing three different modes of intermetallic connectivity. The options for incorporating different 4f ions in an investigative synthesis, without altering the resulting intermetallic core structure, were successful for the three representative examples. Single-crystal X-ray diffraction studies revealed that the compounds are isostructural and built from two initially formed partial dicubane-type Co2Ln2L2 units. In each of the tetranuclear parts, the metal ion centers are held together by two L2-, two μ3-HO-, three Piv- bridges, one terminal Piv-, and one terminal MeOH. Four carboxylate ends of four L2- units are responsible for connecting two Co2Ln2 units into octanuclear structures. The unique distortion around the CoII centers is achieved from the facile coordination of bigger 4f ions to the adjacent hard OO sites. The distortion is further maintained by the presence of terminal COO- groups from L2-. The dc magnetic susceptibility data revealed ferromagnetic coupling between the CoII and LnIII centers within the series, whereas the ac magnetic susceptibility measurements identified only 1, having a highly anisotropic DyIII ion, as a single-molecule magnet in the absence of any external magnetic field, with an energy barrier Ueff of 12.5 K.

Development of a functional impedimetric immunosensor for accurate detection of thyroid-stimulating hormone.

Thyroid-stimulating hormone (TSH), which regulates the synthesis of thyroid gland hormones affecting the whole metabolism, is a pituitary hormone. Determination of TSH is crucial for monitoring thyroid gland-related disorders and some metabolic diseases.In this study, a nonlabeled immunosensor based on covalent immobilization of anti-TSH antibody by using the formation of self-assembled monolayers (SAM) of 4-mercaptophenylacetic acid (4-MPA) and functionalization of carboxyl ends with 1-ethyl-3-(3-dimetilaminopropil) carbodiimide (EDC)/N-Hydroxysuccinimide (NHS) was fabricated for detection of TSH. Immobilization steps including the concentration of 4-MPA, the concentration of anti-TSH antibody, and duration of anti-TSH antibody incubation were optimized by utilizing electrochemical impedance spectroscopy. Under optimal conditions, a sensitive, rapid, and accurate determination of TSH at a concentration range between 0.7 and 3.5 mIU/L was accomplished with a notable linearity and LOD value of 0.034 mIU/L, as well as reproducibility and repeatability. Moreover, for comparison, linear range experiments were also carried out by using other electrochemical methods, including linear sweep voltammetry, cyclic voltammetry, and capacitance spectroscopy. Finally, the constructed immunosensor was used for analyzing TSH levels spiked in the artificial serum samples.

Highly selective and sensitive sandwich immunosensor platform modified with MUA-capped GNPs for detection of spike Receptor Binding Domain protein: A precious marker of COVID 19 infection

A label-free electrochemical biosensing system as a suitable analysis technique for COVID 19 specific spike receptor-binding domain protein (RBD) was developed with an aim to facilitate the diagnosis of coronavirus. A novel production procedure for the fabrication of gold nanoparticles (GNPs)-capped 11-mercaptoundecanoic acid (MUA) modified bioelectrode was presented and its application potential for RBD biosensing was examined. The bioelectrode fabrication protocol was based on covalent ester linking formation between hydroxylated ITO electrode and GNPs-capped MUA (GNPs@MUA) with carboxyl ends. For this aim, spherical GNPs were prepared and characterized with scanning-transmission electron microscopy (S-TEM), UV–vis, and Raman spectroscopy. The synthesized GNPs were functionalized with MUA yielding Au-S bonds. Then, covalent immobilization of anti-RBD antibodies on the GNPs@MUA was performed with the help of carbodiimide coupling chemistry. The assembly processes of GNPs@MUA, anti-RBD antibodies and RBD antigens were characterized electrochemical, chemical and morphological techniques. GNPs@MUA was used as immobilization environment and provided the most effective surface design for target immunosensor. The resulting immunosensor is further applied to the impedimetric detection of RBD and it displayed a linear response to RBD antigen in the linear range of 0.002−100 pg mL−1 with a limit of detection of 0.577 fg mL−1 and sensitivity of 0.238 kohmpgmL−1 cm−2. The fabricated immunosensor had a good repeatability, long storage, stability and a reusable property after simple regeneration process. Furthermore, it was successfully employed for selective determination of RBD in artificial nasal secretion samples.

Toward Quantitative Sequencing of Deuteration of Unsaturated Hydrocarbon Chains in Fatty Acids.

No general method currently is available for the quantitative determination of deuterium (D) at C positions along a hydrocarbon chain. Bis-allylic deuterated highly unsaturated fatty acids (D-HUFA) are a novel class of drugs stabilized against H-abstraction-mediated oxidation by deuteration at the most labile positions. Ru-based catalytic deuteration overcomes the limited scale of bis-allylic D-HUFA production by total organic synthesis; however, it produces a complex mixture of bis-allylic D isotopologues and isotopomers, requiring detailed sequencing for characterization. We report here adaptation and application of the Paternó-Büchi (PB) reaction of 2-acetylpyridine to a series of D-HUFA with analysis by shotgun lipidomics to determine position-specific quantitative D abundances. Sodiated PBD-HUFA result in diagnostic ions of high abundance upon collision-induced dissociation (CID) activation, enabling sensitive differentiation and quantification of D fraction at each bis- and mono-allylic position for each isotopologue. Catalytically deuterated isotopologues D5-7 linolenic acid (D5-7 LnA), D6-8 arachidonic acid (D6-8 ARA), D7-9 eicosapentaenoic acid (D7-9 EPA), and D9-11 docosahexaenoic acid (D9-11 DHA) incorporate 80-98, 95-100, 81-100, and 83-100% D at their bis-allylic positions, respectively. D-HUFA isotopologues having D number greater than or equal to bis-allylic sites (e.g., D10-DHA or D11-DHA) deuterated >95% at bis-allylic positions, except for D-LnA. The mono-allylic position near the methyl end deuterates to a much greater extent than the mono-allylic position near the carboxyl end, and both positions deuterate only when bis-allylic D is near-saturated. This method enables rapid, accurate characterization of position and isotopomer-specific D composition and enables sequencing along the chain.

Use of Half-Generation PAMAM Dendrimers (G0.5-G3.5) with Carboxylate End-Groups to Improve the DACHPtCl2 and 5-FU Efficacy as Anticancer Drugs.

The DACHPtCl2 compound (trans-(R,R)-1,2-diaminocyclohexanedichloroplatinum(II)) is a potent anticancer drug with a broad spectrum of activity and is less toxic than oxaliplatin (trans-l-diaminocyclohexane oxalate platinum II), with which it shares the active metal fragment DACHPt. Nevertheless, due to poor water solubility, its use as a chemotherapeutic drug is limited. Here, DACHPtCl2 was conjugated, in a bidentate form, with half-generation PAMAM dendrimers (G0.5–G3.5) with carboxylate end-groups, and the resulting conjugates were evaluated against various types of cancer cell lines. In this way, we aimed at increasing the solubility and availability at the target site of DACHPt while potentially reducing the adverse side effects. DNA binding assays showed a hyperchromic effect compatible with DNA helix’s disruption upon the interaction of the metallodendrimers and/or the released active metallic fragments with DNA. Furthermore, the prepared DACHPt metallodendrimers presented cytotoxicity in a wide set of cancer cell lines used (the relative potency regarding oxaliplatin was in general high) and were not hemotoxic. Importantly, their selectivity for A2780 and CACO-2 cancer cells with respect to non-cancer cells was particularly high. Subsequently, the anticancer drug 5-FU was loaded in a selected metallodendrimer (the G2.5COO(DACHPt)16) to investigate a possible synergistic effect between the two drugs carried by the same dendrimer scaffold and tested for cytotoxicity in A2780cisR and CACO-2 cancer cell lines. This combination resulted in IC50 values much lower than the IC50 for 5-FU but higher than those found for the metallodendrimers without 5-FU. It seems, thus, that the metallic fragment-induced cytotoxicity dominates over the cytotoxicity of 5-FU in the set of considered cell lines.