Polyamine Groups Research Articles

Spermidine constitutes a key determinant of motility and attachment of Salmonella Typhimurium through a novel regulatory mechanism

Spermidine is a poly-cationic molecule belonging to the family of polyamines and is ubiquitously present in all organisms. Salmonella synthesizes, and harbours specialized transporters to import spermidine. A group of polyamines have been shown to assist in Salmonella Typhimurium's virulence and regulation of Salmonella pathogenicity Inslad 1 (SPI-1) genes and stress resistance; however, the mechanism remains elusive. The virulence trait of Salmonella depends on its ability to employ multiple surface structures to attach and adhere to the surface of the target cells before invasion and colonization of the host niche. Our study discovers the mechanism by which spermidine assists in the early stages of Salmonella pathogenesis. For the first time, we report that Salmonella Typhimurium regulates spermidine transport and biosynthesis processes in a mutually inclusive manner. Using a mouse model, we show that spermidine is critical for invasion into the murine Peyer’s patches, which further validated our in vitro cell line observation. We show that spermidine controls the mRNA expression of fimbrial (fimA) and non-fimbrial adhesins (siiE, pagN) in Salmonella and thereby assists in attachment to host cell surfaces. Spermidine also regulated the motility through the expression of flagellin genes by enhancing the translation of sigma-28, which features an unusual start codon and a poor Shine-Dalgarno sequence. Besides regulating the formation of the adhesive structures, spermidine tunes the expression of the two-component system BarA/SirA to regulate SPI-1 encoded genes. Thus, our study unravels a novel regulatory mechanism by which spermidine exerts critical functions during Salmonella Typhimurium pathogenesis.

Carboxyl and polyamine groups functionalized polyacrylonitrile fibers for efficient recovery of copper ions from solution.

Heavy metals (e.g., Cu) in wastewater are attractive resources for diverse applications, and adsorption is a promising route to recovery of heavy metals from wastewater. However, high-performance adsorbents with high adsorption capacity, speed, and stability remain challenging. Herein, chelating fibers were prepared by chemically grafting amine and carboxyl groups onto the polyacrylonitrile fiber surface and used in the wastewater's adsorption of Cu2+. The adsorption behavior of Cu2+ on the fibers was systematically investigated, and the post-adsorption fibers were comprehensively characterized to uncover the adsorption mechanism. The results show that chelated fiber has a 136.3mg/g maximum capacity for Cu2+ adsorption at pH = 5, and the whole adsorption process could reach equilibrium in about 60min. The adsorption process corresponds to the quasi-secondary kinetic and Langmuir models. The results of adsorption, FTIR, and XPS tests indicate that the synergistic coordination of -COOH and -NH2 plays a leading role in the rapid capture of Cu2+. In addition, introducing hydrophilic groups facilitates the rapid contact and interaction of the fibers with Cu2+ in the solution. After being used five times, the fiber's adsorption capacity remains at over 90% of its original level.

Co-administration of curcumin and polyamines in high-fat diet induced obese rats: Assessment of changes in serum polyamine levels and some tissue parameters

Obesity is a non-communicable chronic disease that continues to increase around the world. Recently, it has been shown that curcumin positively affects lipid, energy metabolism, and body weight change. Moreover, polyamines are aliphatic polycations, which can be found in all mammalian cells and foods and have been shown to prevent obesity through many different mechanisms. However, whether the co-administration of curcumin and polyamines has synergistic effects has yet to be clarified. Our study aimed to examine the effects of curcumin and polyamines on obesity and to assess the changes in serum polyamine levels and tissue parameters. 28 Sprague-Dawley male rats were fed a high-fat diet for 10 weeks to develop obesity, and then they were randomly divided into 4 groups as the control group (CONT), curcumin group (CUR), polyamine group (POL), curcumin and polyamine group (CUR+POL) and supplements were administered for 6 weeks. As a result, the lowest feed consumption in rats was recorded in the CUR+POL group, and the group with the lowest weight after supplements was the POL group, then the CUR+POL, CONT, and CUR groups, respectively. N-acetyl putrescine and GABA levels increased significantly after obesity development. The total histopathological score in fat, liver, and kidney tissues increased significantly in the CONT group. In the CUR+POL group, damage to the tissues was in the direction of recovery compared to the other groups, and the expression of NF-κB was significantly low. These results suggest that combined curcumin and polyamines may have protective effects.

Quantitative Attribution of the Protective Effects of Aminosterols against Protein Aggregates to Their Chemical Structures and Ability to Modulate Biological Membranes.

Natural aminosterols are promising drug candidates against neurodegenerative diseases, like Alzheimer and Parkinson, and one relevant protective mechanism occurs via their binding to biological membranes and displacement or binding inhibition of amyloidogenic proteins and their cytotoxic oligomers. We compared three chemically different aminosterols, finding that they exhibited different (i) binding affinities, (ii) charge neutralizations, (iii) mechanical reinforcements, and (iv) key lipid redistributions within membranes of reconstituted liposomes. They also had different potencies (EC50) in protecting cultured cell membranes against amyloid-β oligomers. A global fitting analysis led to an analytical equation describing quantitatively the protective effects of aminosterols as a function of their concentration and relevant membrane effects. The analysis correlates aminosterol-mediated protection with well-defined chemical moieties, including the polyamine group inducing a partial membrane-neutralizing effect (79 ± 7%) and the cholestane-like tail causing lipid redistribution and bilayer mechanical resistance (21 ± 7%), linking quantitatively their chemistry to their protective effects on biological membranes.

Covalent functionalization of graphene sheets for plasmid DNA delivery: experimental and theoretical study.

Several approaches, including plasmid transfection and viral vectors, were used to deliver genes into cells for therapeutic and experimental purposes. However, due to the limited efficacy and questionable safety issues, researchers are looking for better new approaches. Over the past decade, graphene has attracted tremendous attention in versatile medical applications, including gene delivery, which could be safer than the traditional viral vectors. This work aims to covalently functionalize pristine graphene sheets with a polyamine to allow the loading of plasmid DNA (pDNA) and enhance its delivery into cells. Graphene sheets were successfully covalently functionalized with a derivative of tetraethylene glycol connected to polyamine groups to improve their water dispersibility and capacity to interact with the pDNA. The improved dispersibility of the graphene sheets was demonstrated visually and by transmission electron microscopy. Also, it was shown by thermogravimetric analysis that the degree of functionalization was about 58%. Moreover, the surface charge of the functionalized graphene was +29 mV as confirmed by zeta potential analysis. The complexion of f-graphene with pDNA was achieved at a relatively low mass ratio (10 : 1). The incubation of HeLa cells with f-graphene loaded with pDNA that encodes enhanced green fluorescence protein (eGFP) resulted in the detection of fluorescence signal in the cells within one hour. f-Graphene showed no toxic effect in vitro. Density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM) calculations revealed strong binding with ΔH 298 = 74.9 kJ mol-1. QTAIM between the f-graphene and a simplified model of pDNA. Taken together, the developed functionalized graphene could be used for the development of a new non-viral gene delivery system.

H2O2-mediated tannin bio-based wood adhesive inspired by starfish structure and phenol-amine synergy

High-performance formaldehyde-free bio-based wood adhesives are extremely attractive because of the friendliness and sustainability of their ingredients and resources. This work reports a phenol-amine synergistic tannin bio-based adhesive inspired and designed by insect exoskeleton hardening and starfish structure. The phenol-amine synergistic strategy is based on Schiff base reaction and Michael addition between the benzoquinone group of tannin acid (TA) and the nucleophilic amino group of polyamines (PA XN , X = 4, 5 and 6, X represent the number of amino-terminal groups), which is supplemented by oxidation-induced quinone cross-linking in TA and the combination of covalent and non-covalent bonds. The proposed TAPA wood adhesives with the three-dimensional dense cross-linking network may dissipate stress via hiding sacrificial bonds, which can form a compact glue film to prevent the infiltration of water molecules as well as increase thermal resistance. FT-IR, XPS, and solid 13 C NMR demonstrated the tannin-based phenol-amine network was formed by cross-linking imine covalent bonds. DSC, TG, and DMA revealed reduced melting and glass transition temperatures, as well as improved thermal stability, which are conducive to the cross-linking and curing of adhesives. In detail, the dry lap shear strength of TAPA adhesive increased by 170% from 0.8 MPa to 2.16 MPa compared with pure TA adhesive by using poplar veneer as wood substrate; and the wet lap shear strength made a breakthrough from 0 to 1.06 MPa, exceeding the minimum requirement (0.7 MPa) defined by the China national standard (GB/T 17657–2013). Given this, a high-efficiency, green, and economic phenol-amine synergistic strategy are beneficial to the development of formaldehyde-free bio-based wood adhesives and multifunctional application of agricultural and forestry residues. Schematic illustration of developing phenol-amine synergetic TAPA wood adhesive inspired by insect exoskeleton hardening. • Tannin-based wood adhesives were prepared by phenol-amine synergy strategy. • FT-IR, XPS, 13C NMR, SEM, DSC, TG, and DMA characterization were carried. • Phenol-amine cross-linking network connected by covalent bonds and non-covalent bonds. • TAPA adhesives showed enhanced bonding strength, waterproof and thermal properties. • The formation of cross-linking network help to improve the performance.

In silico investigation of the therapeutic and prophylactic potential of medicinal substances bearing guanidine moieties against COVID-19.

The current viral pandemic, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), creates health, mental, economic, and other serious challenges that are better to say global crisis. Despite the existence of successful vaccines, the possible mutations which can lead to the born of novel and possibly more dangerous variants of the virus as well as the absence of definitive treatment for this potentially fatal multiple-organ infection in critically ill patients make us keep searching. Theoretically targeting human and viral receptors and enzymes via molecular docking and dynamics simulations can be considered a wise, rational, and efficient way to develop therapeutic agents against COVID-19. In this way, The RNA-dependent RNA polymerase (RdRP), main protease, and spike glycoprotein of SARS-CoV-2 as well as the human angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 are the most discussed and studied targets that play essential roles in the viral life and infection cycle. In the current in silico investigation, the guanidine functionality containing drugs and medicinal substances such as metformin, famotidine, neuraminidase inhibitors, antimalarial medications, anticancer drug imatinib, CGP compounds, and human serine protease inhibitor camostat were studied against the above-mentioned therapeutic targets and most of them (especially imatinib) have revealed an incredible spectrum of free docking scores and MD results. The current in silico investigation that its novel perspective of view is corroborated by the different experimental and clinical evaluations, confirms that the guanidine moiety can be considered as a missing promising pharmacophore in drug design and development approaches against SARS-CoV-2. Considering the chemical potency of this polyamine group in chemical interaction creation, the observed outcomes in this virtual screening were not surprising. On the other hand, the guanidine functional group has unique physico-chemical properties such as basicity that can make the target cells intracellular pH undesirable for the virus entry, uncoating, and cytosolic lifecycle. According to the obtained results in the current study that are interestingly confirmed by the previously reported efficacy of some the guanidine carrying drugs in COVID-19, guanidine as a potential multi-target anti-SARS-CoV-2 functional scaffold deserves further comprehensive investigations.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s11696-022-02528-y.

Ion exchange recovery of rhodium from strong ammonium chloride solutions

The authors looked at the sorption of rhodium using Puromet MTS9840, Puromet MTS9841 and Puromet MTS9850 weakly basic anion exchange resins with polyamine groups and Puromet MTS9140 ion exchange resin with thiourea groups, and they found that, when HCl is partially replaced with NH4Cl as the source of chloride ions and if the overall concentration of chloride ions remains the same (i.e. 4 mol/l), the rhodium distribution coefficients tend to drop in direct proportion to the rising share of NH4Cl in the solution. When using a mixture of 1 mol/l HCl and 3 mol/l NH4Cl, the rhodium capacities of all tested ion exchange resins are 2.5 to 6 times lower than the capacities reached when using 4 mol/l HCl solutions, with the steady-state concentrations of rhodium being equal. The sorption isotherms for the NH4Cl containing solution remain arc-shaped. At the same time, the presence of NH4Cl is associated with only a slight decrease in the rhodium sorption rates when using polyamine resins, which is demon strated in the case of the MTS9840 resin. In terms of selectivity and rhodium capacity when using chloride solutions both with and without ammonium chloride, the tested ion exchange resins can be arranged as follows: MTS9841 > MTS9840 > MTS9140 > MTS9850. It was found that when rhodium is absorbed in dynamic conditions from the following solution, g/l: Rh(III) 0,2; NH4Cl 133,7 (2.5 mol/l); HCl 54,7 (1.5 mol/l); Fe(III) 5,0; Al(III) 4,2; Zn(II) 4,0; Sn(IV) 6,0, the use of the MTS9841 anion exchange resin results in a higher recovery of rhodium (up to 98%), while the residual concentration of rhodium in the solution drops 4 times (down to 0.005 g/l) as compared with the use of the MTS9840 anion exchange resin. It is shown that the process of rhodium desorption from saturated MTS9841 anion exchange resin with a acidified thiourea solution has a minimum rate of 95%. This research was funded by the Russian Science Foundation; Project No. 21-79-30029.

Polyamine-functionalized imidazolyl poly(ionic liquid)s for the efficient conversion of CO2 into cyclic carbonates

The synergistic effect of polyamine groups and nucleophile (Br−) significantly improved the catalytic performance of N4-PIL-2, which can convert epoxides into cyclic carbonates with excellent yields and selectivity under ambient pressure.

Polyamine-modified polyacrylonitrile fibers for efficient removal of U(VI) from real fluorine-contained low-level radioactive wastewater

It is of great significance to develop an adsorbent with high adsorption capacity and excellent resistance to anion and cation interference toward the removal of U(VI). Herein, a novel polyamine-modified polyacrylonitrile-based fiber (PANPA) has been synthesized through hydrothermal method, which can validly remove U(VI) from solution. Combined with mesoscopic, spectral characterization and simulation method, the removal behavior and mechanism of U(VI) from high fluorine uranium-containing wastewater by PANPA are systematically investigated. The results show that, based on the strong coordination principle of polyamine group and UO22+, PANPA can selectively remove U(VI) from wastewater. In addition, the qmax of 459.27 mg g−1 was more than that of many other adsorbent materials. More importantly, PANPA is not affected by high concentration of F−, and exhibits higher distribution coefficient (559,900 mL g−1) and removal efficiency (99.5%) to U(VI) than other coexisting ions in real wastewater. Furthermore, the column experiment was also implemented to remove U(VI). The results indicate that PANPA is a promising material to effectively remove U(VI) from real wastewater produced during the fabrication of nuclear fuel elements.

Synthesis of poly(styrene‐co‐allylamine)‐b‐poly(2‐(dimethylamino)ethyl methacrylate) graft copolymers via “grafting from” atom transfer radical polymerization and their self‐assembly in aqueous media

AbstractIn this work, we report a new synthetic scheme for synthesis of graft copolymers. At first, poly(styrene‐co‐acrylonitrile) copolymers with different molecular weights were synthesized via atom transfer radical polymerization (ATRP). Then, lithium aluminum hydride was used as reducing catalyst of nitrile groups to obtain poly(styrene‐co‐allylamine) copolymers. Amine groups of poly(styrene‐co‐allylamine) copolymers were reacted to 2‐bromo‐2‐methylpropionyl bromide (BiBB) to yield poly(styrene‐co‐N‐allyl‐2‐bromo‐2‐methylpropanamide) (poly(styrene‐co‐NABMPA)) as macroinitiator for “grafting from” ATRP. Then, ATRP of 2‐(dimethylamino)ethyl methacrylate (DMAEMA) was performed to graft PDMAEMA side chains. Finally, self‐assembly behavior of synthesized graft copolymers was investigated in aqueous media with different pH values and morphology of obtained supramolecular structures was studied. Synthesized copolymers were well‐characterized by 1H NMR, 13C NMR, and gel permeation chromatography. Also, morphology of self‐assembled structures was studied by FE‐SEM images whereas dynamic light scattering was utilized to measure particle size and particle size distribution. Results showed that morphology of self‐assembled supramolecular structures depended on molecular weight of backbone and pH value of media. By changing the self‐assembly conditions, different morphologies including spherical, Janus, and interconnected Janus were obtained.

Polyamine functionalized cotton fibers selectively capture negatively charged dye pollutants

Cotton fiber was functionalized with polyamine polymer PEI by a facile and eco-friendly method. The structural and chemical characteristics of the resulting PEI@cotton were investigated using various analysis techniques and the adsorption performance of the PEI@cotton was tested by removing organic dye pollutant from aqueous solutions. The incorporation of polyamine groups on the cotton fiber surface enabled PEI@cotton to selectively remove negatively charged organic dye pollutants from aqueous solution, and significantly outperformed, in terms of rate and capacity, untreated cotton fiber. The isotherm study indicated that the absorption of MO and XO by PEI@cotton obeyed the Langmuir model, and the maximum adsorption values were 755.7 mg/g and 303.4 mg/g, respectively. Kinetic experiments confirmed that the pseudo-second-order model was more suitable for describing the adsorption data. The possible adsorption mechanism of PEI@cotton to negatively charged dye contaminants has been provided. Furthermore, PEI@cotton can be regenerated multiple times through a simple operation with no significant loss of performance. Overall results of adsorption indicated that the PEI@cotton was a promising material for rapid and efficient adsorption of negatively charged dyes from aqueous solution. It is hoped that the facile and scalable methodology described in this work can provide ideas for the production of environmentally friendly water treatment materials.

Highly selective removal of Ni(II) from plating rinsing wastewaters containing [Ni-xNH3-yP2O7]n complexes using N-chelating resins

Inorganic complexants, such as ammonia (AA) and pyrophosphate (PP), are often present alongside heavy metal ions in alkaline plating rinsing wastewater. We investigated the removal capacity of Ni(II) from waters containing [Ni-xNH3-yP2O7]n complexes by chelating and ion-exchange resins in sole and dual-ligand systems. D463 (containing iminodiacetic groups) and PAMD (possessing polyamine groups) exerted superior performance under all conditions. Ni(II) adsorption on D463 decreased with AA and PP by 10.3% and 64.4%, respectively. Conversely, the adsorption on PAMD increased by 57.3% and 75.8%, respectively. PAMD exhibited high selectivity toward anionic [Ni-PP] species over free PP. More Ni(II) was captured by PAMD in the dual-ligand systems than sole systems, while the case for D463 was opposite. As confirmed by species tracking and DFT/XPS analyses, complexes breaking-Ni2+ capture was the dominant mechanism for D463, while the dual-site (non-charged and protonated amines) interactions with NiP2O72– on PAMD promoted its adsorption. The tandem combination D463-PAMD was the optimal mode to remove the most Ni(II). The actual wastewater test demonstrated that >210 BV effluent met the limit of 0.1 mg Ni(II)/L and the eluent contained 15 g Ni(II)/L. This study guides the application of chelating adsorption processes in the advanced treatment of plating rinsing wastewaters.

Novel insights into the competitive adsorption behavior and mechanism of per- and polyfluoroalkyl substances on the anion-exchange resin

Per- and polyfluoroalkyl substances (PFASs) are widely used and co-exist in various aquatic environments, but their co-removal is not clear. In this study, the competitive adsorption behavior and mechanism of six traditional and emerging PFASs on anion-exchange resin IRA67 in the bisolute and mixed systems were studied. The adsorption equilibrium of the long-chain PFASs was at least 96 h whereas 48 h was required for the short-chain PFASs. When the PFASs were co-removed in the bisolute system, their competition was not obvious at low PFAS concentration of 0.01597 mmol/L due to the relatively adequate adsorption sites. When the concentrations of PFASs were increased to 0.07666 mmol/L, the removal of perfluorobutanoic acid (PFBA) and perfluorobutane sulfonate (PFBS) decreased by 77.78% and 72.09%, respectively. The competitive experiments showed that the adsorbed short-chain PFASs could be replaced by the long-chain ones, which was closely related to their hydrophobicity, backbone and functional groups. With the increase of solution pH from 3 to 7, the polyamine groups on the resin IRA67 were transferred to the base forms and the effective adsorption sites decreased, resulting in a more obvious competitive replacement behavior. This study suggested that the PFASs with long chain could be more effectively removed from the coexisting PFASs solution by the anion-exchange resins, and the short-chain PFASs in water may be removed when high dosage of anion-exchange resins is applied or the solution pH is decreased.

Derivatives of closo-Decaborate Anion with Polyamines

The reactions of 1,4-dioxane derivative of closo-decaborate anion with hydrazine and a number of polyamines (tetraethylenepentamine, triethylenetetramine, tris(2-aminoethyl)amine, bis(3-aminopropyl)amine, and N,N'-bis(3-aminopropyl)-1,4-diaminobutane) in ethanol were studied. It was shown that in these reactions in which polyamines act as nucleophiles, the substituent ring is opened with addition of the corresponding pendant functional group. The obtained derivatives of the closo-decaborate anion with polyamine moieties linked to the boron cluster via an alkoxyl spacer are promising for preparing new substances with potential pharmacological activity for the use in boron neutron capture therapy of malignant tumors. The introduced polyamine groups allow the obtained closo-borates to bind to various polyanionic targets in the cell (DNA, RNA, phospholipids, charged protein sites, etc.). The products were studied by various physicochemical methods (IR and heteronuclear NMR spectroscopy, ESI MS spectrometry).

MRNA dynamics and alternative conformations adopted under low and high arginine concentrations control polyamine biosynthesis in Salmonella.

Putrescine belongs to the large group of polyamines, an essential class of metabolites that exists throughout all kingdoms of life. The Salmonella speF gene encodes an inducible ornithine decarboxylase that produces putrescine from ornithine. Putrescine can be also synthesized from arginine in a parallel metabolic pathway. Here, we show that speF expression is controlled at multiple levels through regulatory elements contained in a long leader sequence. At the heart of this regulation is a short open reading frame, orf34, which is required for speF production. Translation of orf34 interferes with Rho-dependent transcription termination and helps to unfold an inhibitory RNA structure sequestering speF ribosome-binding site. Two consecutive arginine codons in the conserved domain of orf34 provide a third level of speF regulation. Uninterrupted translation of orf34 under conditions of high arginine allows the formation of a speF mRNA structure that is degraded by RNase G, whereas ribosome pausing at the consecutive arginine codons in the absence of arginine enables the formation of an alternative structure that is resistant to RNase G. Thus, the rate of ribosome progression during translation of the upstream ORF influences the dynamics of speF mRNA folding and putrescine production. The identification of orf34 and its regulatory functions provides evidence for the evolutionary conservation of ornithine decarboxylase regulatory elements and putrescine production.

Adsorption behavior and mechanism of emerging perfluoro-2-propoxypropanoic acid (GenX) on activated carbons and resins

As a typical alternative to perfluorooctanoic acid (PFOA), perfluoro-2-propoxypropanoic acid (GenX) has been detected worldwide in aquatic environment and attracted great concerns recently, but their adsorptive removal from water is not clear. In this study, the adsorption behavior and mechanism of GenX on granular activated carbon (GAC), powdered activated carbon (PAC), anion-exchange resins (IRA400 and IRA67) were compared. The particle size of activated carbon (AC) affected the initial adsorption rate but exhibited little influence on the adsorption capacity for GenX. The initial adsorption kinetics of GenX on the three granular adsorbents (GAC, IRA67 and IRA400) followed the intraparticle diffusion-controlled adsorption. IRA67 had the highest adsorption capacity of 3.22 mmol/g for GenX, higher than IRA400 (2.78 mmol/g) and much higher than the two ACs (0.79 mmol/g). When GenX was co-removed with perfluorooctanoic acid (PFOA) in competitive system, the adsorbed amounts of GenX on the four adsorbents decreased significantly, and adsorbed GenX was replaced by PFOA with increasing time. The small adsorbent size could speed up the replacement process, and the polyamine group on the resins was more prone to producing this effect than the quaternary ammonium group. PAC was more suitable for GenX removal at low pH, while IRA400 was better used at high solution pH. The spent AC and resins were successfully regenerated in the ethanol and NaCl solution, respectively, and their regeneration efficiency was significantly enhanced in hot water. The adsorption mechanisms including anion exchange, electrostatic interaction and hydrophobic interaction were involved in the GenX adsorption.

PH-responsive polymeric micelles with tunable aggregation-induced emission and controllable drug release

Stimuli-responsive polymeric micelles as a drug delivery vehicle have made important contributions to the development of controllable drug release. Here we develop pH-responsive polymeric micelles with tunable aggregation-induced emission and controllable drug release. Polymeric micelles in nano-sized spherical shape (about 140 nm) were mediated via hydrogen-bonding interaction between phenol groups of 4,4′-(1,2-diphenylethene-1,2-diyl)diphenol (TPE-2OH) and amine groups of poly(ethylene glycol)-block-linear polyethylenimine-block-poly(e-caprolactone) (PEG-PEI-PCL). The results show that polymeric micelles are pH-responsive with turn-on fluorescence and sustained drug release inside cells, which has hope in simultaneously achieving cell imaging and cancer therapy.

Molecular Dynamics Simulations on Nucleic Acid Binding Polymers Designed To Arrest Thrombosis.

Cancer-associated thrombosis is managed by the administration of anticoagulants and antithrombotic agents that have a high risk of inducing hemorrhagic complications. To develop safer strategies for antithrombotic therapy, in vivo activators of the intrinsic pathway, namely, cell-free nucleic acids (DNA and RNA) have been targeted with cationic, polyamine-based polymers. The cytotoxicity of the highly cationic polymers is a major drawback for their practical use, and biocompatible alternatives are in high demand. In this study, we carried out all-atom molecular dynamics simulations to systematically examine the DNA binding of polyamine-poly(ethylene glycol) (PEG) diblock polymers designed from biocompatible building blocks to inhibit the procoagulant activity of DNA. The differences in cationic charge, PEG chain length, and initial conformations of the polymers resulted in marked differences in their binding to DNA. We found that having an exposed cationic polyamine group is essential to polymer-DNA binding and a certain level of electrostatic interactions is necessary to maintain the bound state. Intrachain associations between the polyamine groups and PEG chains in some cases have led to a collapsed state of the polymer that precludes binding to DNA. This self-association is mainly due to a strong hydrogen bond between polymer polyamine and PEG groups and partly due to a partially charged semibranched polyamine group architecture. As polymer "masking" of DNA is thought to arrest DNA's prothrombotic activity, our findings highlight the desired structural features of the polymers for stronger DNA binding and provide insights into the design of novel antithrombotic agents.

Copper(II) complexes of N3O tripodal ligands appended with pyrene and polyamine groups: Anti-proliferative and nuclease activities

A series of tripodal ligands based on the 2-tert-butyl-4-R-6-phenol was synthesized, where R=aldehyde (HL1), R=putrescine-pyrene (HL2) and R=putrescine (HL3). A dinucleating ligand wherein a putrescine group connects two tripodal moieties was also prepared (H2L4). The corresponding copper complexes (1, 2, 3, and 4, respectively) were prepared and characterized. We determined the phenol's pKas in the range 2.47–3.93. The DNA binding constants were determined at 6×106, 5.5×105 and 2.7×106 for 2, 3 and 4, respectively. The complexes display a metal-centered reduction wave at Epc,red=−0.45 to −0.5V vs. saturated calomel electrode, as well as a ligand-centered oxidation wave above 0.57V at pH7. In the presence of ascorbate they promote an efficient cleavage of DNA, with for example a concentration required to cleave 50% of supercoiled DNA of 1.7μM for 2. The nuclease activity is affected by the nature of the R group: putrescine-pyrene≈bis-ligating>putrescine>aldehyde. The species responsible for strand scission is the hydroxyl radical. The cytotoxicity of the complexes was evaluated on bladder cancer cell lines sensitive or resistant to cis-platin. The IC50 of complexes 2 and 4 span over a short range (1.3–2μM) for the two cell lines. They are lower than those of the other complexes (3.1–9.7μM) and cis-platin. The most active compounds block the cell cycle at the G0/1 phase and promote apoptosis.