Terminal Aldehyde Group Research Articles

Photodynamic therapy of fullerene modified with pullulan on hepatoma cells

To design a novel cytospecific photosensitizer for photodynamic antitumor therapy, a fullerene (C60) was chemically modified with pullulan which is a water-soluble polysaccharide with a high affinity for asialoglycoprotein receptors. Ethylene diamine was introduced to the terminal aldehyde groups of pullulan by the reductive amination reaction. Pullulan was coupled to C60 through the terminal amine group. The C60 end-group conjugated with pullulan was water-soluble and generated superoxide anion upon light irradiation. The C60–pullulan conjugates significantly suppressed the in vitro growth of HepG2 hepatoma cells with asialoglycoprotein receptors, while less suppression activity was observed for HeLa cells without the receptors. The conjugates have a high binding affinity for HepG2 cells, in contrast to HeLa cells. When C60 was conjugated with polyethylene glycol (PEG) with the similar molecular weight in order to compare the in vitro cell binding and antitumor activities with the C60–pullulan conjugate, the dependence of cell type on their activities was not observed. Following the intravenous injection of C60–pullulan conjugates to mice carrying a subcutaneous mass of HepG2 cells, significant stronger photodynamic effect on tumor was observed than the intravenous injection of C60–PEG conjugates and saline. It is concluded that the pullulan conjugation gave C60 the targetability to HepG2 cells, resulting in enhanced photodynamic tumor therapy effect.

Clean and Flexible Modification Strategy for Carboxyl/Aldehyde‐Functionalized Upconversion Nanoparticles and Their Optical Applications

AbstractRare‐earth upconversion nanoparticles (UCNPs) exhibit great potential in luminescent biolabels and other multifunctional probes; however, their applications are limited by their low water solubility and the lack of binding groups. To address these problems, a clean and flexible strategy to modify hydrophobic monodisperse UCNPs into hydrophilic ones that are capped with functional groups is developed. The modification process is implemented by direct oxidation of oleic acid ligands with ozone under specific conditions, where the oleic acid (OA) ligands on the surface of the UCNPs can be converted into azelaic acid ligands (HOOC(CH2)7COOH) or azelaic aldehyde HOOC(CH2)7CHO, as is revealed by Fourier‐transform infrared (FTIR) and nuclear magnetic resonance (NMR) measurements. This oxidation process has no significant side‐effects on the morphology, phase, composition, or luminescent properties of the UCNPs. Free carboxylic acid groups on the surface endow the UCNPs with good water solubility, while aldehyde groups at the surface provide binding sites for amino‐containing molecules via Schiff‐base condensation, such as 2‐(4‐aminophenylethylyl)‐5‐methoxy‐2‐(2‐pyridyl)thiazole (MPTEA) and 2‐aminoethanethiol hydrochloride (NH2CH2CH2SH·HCl, HEMA). A Ce4+ sensor is constructed based on the dual‐emission arising from the different spectral responses of MPTEA and the UCNPs. Facilitated by the covalent linkage between the terminal aldehyde group on the UCNPs and the amino group in HEMA, a hybrid structure of UCNPs and Au NPs is fabricated. The effective coupling between the aldehyde group and the amino group suggests that these functionalized UCNPs have potential in combining other functional units for simultaneous biolabeling, or other optical applications.

Bifunctional oligo(ethylene glycol) decorated surfaces which permit covalent protein immobilization and resist protein adsorption

In this article, surface coatings derived from homo-bifunctional tri(ethylene glycol) (EG3) and hexa(ethylene glycol) (EG6) molecules which have two terminal aldehyde groups are reported. These homo-bifunctional molecules can be used to functionalize amine-terminated surfaces through crosslinking one aldehyde group to surface amine groups, while leaving the other aldehyde group available for covalent immobilization of proteins. Best of all, after reducing remaining aldehyde groups on the surface with a reducing agent, sodium borohydride, the surface becomes oligo(ethylene glycol) (OEG)-terminated. The OEG-terminated surface can resist nonspecific protein adsorption, a feature that is often required for many biosensors and biomedical devices. Although some mixed self-assembled monolayers formed from two different organothiols also permit covalent protein immobilization and resist nonspecific protein adsorption, the procedure reported herein requires only one type of homo-bifunctional molecule and can be applied to both silicon and gold surfaces.

FTIR and FT-Raman spectra and DFT vibrational analysis of phosphorus-containing dendrons

FTIR and FT-Raman spectra of four generations of phosphorus-containing dendrons with terminal aldehyde or P Cl groups have been recorded and analyzed. Their spectral patterns are determined by the ratio T/ R ( T, the number of terminal groups; R, the number of repeated units). Bands assigned to the core, repeated units and terminal groups were separated by the difference spectroscopy method. The optimized geometry, frequencies and intensity of IR bands of G ′ 1 v generation dendron with terminal aldehyde groups were obtained by the density functional theory (DFT). It was found that the internal skeleton of molecules exists in a single stable conformation with planar O– C 6 H 4 – CH N– N( CH 3 )– P( S)〈 fragments, but terminal groups may adopt the t, g, g- and t,- g, g-rotational isomers. The t,- g, g-conformer is 0.74 kcal/mol less stable compared to the t, g, g-conformer. The bond length and bond angles obtained by DFT show the best agreement with experimental data. Relying on DFT calculations a complete assignment of vibrations is proposed for different parts of the studied dendrons. The calculated frequencies and intensity of IR bands of the t, g, g- and t,- g, g-conformers of G ′ 1 v are found to be in reasonable agreement with the experimental results. The most reactive site in dendron is the core function and vinyl group is preferred for nucleophilic attack. In dendrimer the most reactive are the terminal groups.

Bio-oxidation of tripropylene glycol under aerobic conditions

Aerobic biodegradation of tripropylene glycol (PG3) was investigated under the conditions of the OECD screening test 301E and the Continuous Flow Activated Sludge Simulation test (CFAS). A modified two-chamber facility with a denitrification stage was used for the CFAS test. Primary PG3 biodegradation was measured by the HPLC with fluorimetric detection and analyte derivatisation. Metabolites were identified by LC-MS with electrospray ionisation and GC-MS with electron impact ionisation, as well as semiquantitatively determined by the LC-MS technique. PG3 was found to be inherently biodegradable and it exhibits a strong poisonous effect on activated sludge after exceeding the threshold concentration (10 mg l(-1)). Metabolite accumulation onto the activated sludge is probably responsible for this poisonous effect. Probable biotransformation products of tripropylene glycol under the aerobic conditions include metabolites with a single terminal aldehyde or a ketone group and metabolites with two terminal aldehyde or ketone groups. Their concentration rises at the end of the OECD screening test.

Synthesis of pH-sensitive amphotericin B–poly(ethylene glycol) conjugates and study of their controlled release in vitro

New intravenous conjugates of amphotericin B (AMB) with poly(ethylene glycols) (PEG) ( M = 5000, 10,000, 20,000) have been synthesized and characterised. The intermediate PEGs possess a 1,4-disubstituted benzene ring with aldehyde group at the end of the chain. The benzene ring is connected with PEG at its 4-position (with respect to the aldehyde group) by various functional groups (ether, amide, ester). Reaction of terminal aldehyde group of the substituted PEGs with AMB gave conjugates containing a pH-sensitive imine linkage, which can be presumed to exhibit antimycotic effect at sites with lowered pH value. All types of the conjugates are relatively stable in phosphate buffer at physiological conditions of pH 7.4 (37 °C), less than 5 mol% AMB being split off from them within 24 h. For a model medium of afflicted tissue was used a phosphate buffer (pH 5.5, 37 °C), in which controlled release of AMB from the conjugates takes place. The imine linkage is split to give free AMB with half-lives of 2–45 min. The rate of acid catalysed hydrolysis depends upon substitution of the benzene ring; however, it does not depend on molecular weights of the PEGs used. The conjugates with ester linkage undergo enzymatic splitting in human blood plasma and/or blood serum at pH 7.4 (37 °C) with half-lives of 2–5 h depending on molecular weights of the PEGs used ( M = 5000, 10,000, 20,000). At first, the splitting of ester linkage produces the relatively stable pro-drug, that is, 4-carboxybenzylideniminoamphotericin B, which is decomposed to AMB and 4-formylbenzoic acid in a goal-directed manner only at pH 7 ( t 1/2 = 2 min, pH 5.5, 37 °C). A goal-directed release of AMB is only achieved by acid catalysed hydrolysis of imine linkage, either from the polymeric conjugate or from the pro-drug released thereof. The LD 50 values determined in vivo (mouse) are 20.7 mg/kg and 40.5 mg/kg for the conjugates with ester linkage ( M = 10,000 and 5000, respectively), which means that they are ca. 6–11 times less toxic than free AMB.

Synthesis, reactivity, and pH-responsive assembly of new double hydrophilic block copolymers of carboxymethyldextran and poly(ethylene glycol)

Double hydrophilic block copolymers (DHBC) were prepared by end-to-end coupling of two biocompatible water-soluble homopolymers: the polysaccharide dextran ( M w 8300 or 14,700 g mol −1) and ω-amino poly(ethylene glycol) (PEG–NH 2, M w 3000 or 7000 g mol −1). The synthesis involved, first, specific oxidation of the dextran terminal aldehyde group and, second, covalent linkage of PEG–NH 2 via a lactone aminolysis reaction. The diblock copolymers dextran–PEG (DEX–PEG) were converted in high yield into the corresponding carboxymethyldextran–PEG (CMD–PEG) derivatives with control over the degree of substitution, from 30 to 85 mol% CH 2COOH groups per glucopyranosyl unit. Further modifications of a CMD–PEG block copolymer led to N-(2-aminoethyl)carbamidomethyldextran–PEG yielding a pair of oppositely-charged DHBC of identical charge density, chain length, and neutral block/charged block content. The properties of CMD–PEG in aqueous solutions were studied by static and dynamic light scattering as a function of solution pH, providing evidence of the pH-sensitive assembly of the copolymers driven by inter- and intra-chain hydrogen-bond formation.

The effect of capron substrates on water absorption by some latex films

It is shown that using ammonia to treat films formed on a capron substrate from latexes, whose polymers contain vinylidene chloride units or terminal aldehyde groups, leads to a decrease in water absorption by these films as compared to free films. This result is explained by the formation of nitrogen-containing groups in the latex polymers, with these groups being capable of interacting with polycaproamide.

Group B Streptococcal Type II and III Conjugate Vaccines: Physicochemical Properties That Influence Immunogenicity

Recent efforts toward developing vaccines against group B streptococci (GBS) have focused on increasing the immunogenicity of GBS polysaccharides by conjugation to carrier proteins. However, partial depolymerization of GBS polysaccharides for the production of vaccines is a difficult task because of their acid-labile, antigenically critical sialic acids. Here we report a method for the partial depolymerization of type II and III polysaccharides by mild deaminative cleavage to antigenic fragments with reducing-terminal 2,5-anhydro-d-mannose residues. Through the free aldehydes of their newly formed end groups, the fragments were conjugated to tetanus toxoid by reductive amination. The resulting conjugates stimulated the production in animals of high-titer type II- and III-specific antibodies which induced opsonophagocytic killing of type II and III strains of group B streptococci. For the type II conjugates, immunogenicity increased as oligosaccharide size decreased, whereas for type III conjugates, the size of the oligosaccharides did not significantly influence immunogenicity. When oligosaccharides of defined size were conjugated through sialic acid residues, the resulting cross-linkages were shown to affect immunogenicity. When oligosaccharides were conjugated through terminal aldehyde groups generated by deamination, modification of the exocyclic chain of sialic acid did not influence immunogenicity.

Carbohydrate ligands of human C-reactive protein: Binding of neoglycoproteins containing galactose-6-phosphate and galactose-terminated disaccharide

Binding of carbohydrate ligand by human C-reactive protein (CRP), in both native form and structurally deviated form (neoCRP or mCRP), was investigated using galactose-6-phosphate (Gal6P)- and Galbeta3GalNAc-containing bovine serum albumin (BSA) derivatives. To this end, we synthesized glycosides of Gal6P and Galbeta3GalNAc that can potentially generate a terminal aldehyde group. omega-Aldehydo glycosides were then conjugated to BSA via reductive amination. Using these neoglycoproteins, we showed that: (1) Gal6P-BSA and Galbeta3GalNAc-BSA bound to both forms of CRP, the former with or without calcium and the latter only in the absence of calcium; (2) phosphate-containing ligands can be bound with or without calcium, but the binding is much stronger in the presence of calcium than in the absence, underscoring the importance of direct coordination of phosphate to two calcium ions observed in the X-ray structure of phosphorylcholine (PC)-CRP complex; (3) cross-inhibition studies further corroborated the hypothesis that binding sites of PC and sugar are contiguous; (4) while PC-BSA bound to the native CRP over a wide pH range of 4.5 to 9, all the carbohydrate ligands and protamine-BSA (poly-cation-based ligand) exhibited optimal binding at around pH 6 to 6.5; and (5) ligand-binding conformation of mCRP appears to be more fragile than that of the native CRP in the acidic media (pH < 6).

Preparation and Stability of N-Terminal Mono-PEGylated Recombinant Human Endostatin

Endostatin can specifically inhibit endothelial proliferation and potently inhibit angiogenesis and tumor growth. N-Terminal site-specific mono-PEGylation of recombinant human endostatin (mPEG-rhES) was accomplished by using methoxy poly-ethylene glycol (mPEG) propionaldehyde with an average molecular weight of 5000 Da through a reactive terminal aldehyde group. The site-specific mPEG conjugation was conducted under optimal conditions, which were identified through a statistical L(9)(3(4)) orthogonal test. In this study, we have investigated the stability and antitumor activity of mPEG-rhES. SDS-PAGE, RP-HPLC, and UV spectrophotometric analysis were used to identify the purity and stability of mPEG-rhES. When incubated with protease or placed in an extreme environment, mPEG-rhES was more stable than rhES. The unmodified and PEGylated rhES were tested for their ability to inhibit the tumor growth of mouse H22 liver cancer in male mice. In a multiple versus single doses comparison study, daily administration of 0.25, 0.50, and 1.00 micromol/kg of unmodified rhES for 7 days resulted in 26.9%, 43.0%, and 64.9% reductions in tumor weight, respectively, while single doses of 0.13, 0.25, and 0.50 micromol/kg of the PEGylated protein per day resulted in 24.8%, 38.0%, and 64.5% reductions, respectively. Both treatments resulted in statistically significant reductions in mean tumor weight as compared to the physiological saline solution (control)-treated mice, with the dose of mPEG-rhES being a half of rhES, respectively, while the tumor inhibition rates were similar. Therefore, it is suggested that PEGylation enhances the stability of rhES and improves its antitumor activity.

DFT calculations of structure and IR spectra of the phoshorus-containing G′ 0 v generation dendron

FT-IR spectra of the phosphorus-containing dendron G′ 0 v generation with terminal aldehyde groups have been recorded. The structural optimization and normal mode analysis are performed for the G′ 0 v on the basis of the ab initio density functional theory. This calculations gave vibrational frequencies and infrared intensities for the t, g, g- and t, -g, g-conformers of the G′ 0 v . The t, -g, g-conformer is 0.71 kcal/mol less stable compared to t, g, g-conformer. Relying on DFT calculations a complete vibrational assignment is proposed for different parts of the dendron. The influence of encirclement on band frequencies and intensity is studied and the information usually inaccessible is obtained. The global and local reactivity descriptors have been used to characterize the reactivity pattern of the core function and terminal groups. Our study reveals that the most reactive site in the dendron is the core function and the CH 2 side of the vinyl group is preferred for nucleophilic attack. In the dendrimer the most reactive are the terminal groups.

DFT calculation of molecular structure and vibrational spectra of the phosphorus-containing [formula omitted] generation dendrimer with terminal aldehyde groups

The Raman and infrared spectra of the first generation of the phosphorus-containing dendrimer with terminal aldehyde groups have been recorded. The structural optimization and normal mode analysis are performed for phosphorus-containing dendrimer on the basis of the ab initio density functional theory. This calculations gave vibrational frequencies and infrared intensities for the t,g,g- and t,-g,g-conformers of the terminal groups. The t,g,g-conformer is 0.34 kcal/mol less stable compared to t,-g,g-conformer. It is found that the repeated units of dendrimer exists in a single stable conformation with planar O C 6H 4 CH N N(CH 3) P fragments. All these observations suggest that steric congestion does not disturb the construction of dendrimers even for the highest generations, and that terminal groups are readily available for further reactions. Relying on DFT calculations a complete vibrational assignment is proposed for different parts of the studied dendrimer. Our study reveals that in the G 1 ′ and G 1 dendrimers the most reactive are the terminal groups. IR spectroscopy combined with ab initio DFT computation provides unique detailed information about the structure of the technologically relevant materials, which could not be obtained before with any other technique.

DFT study and vibrational spectra of the phoshorus-containing G0 generation dendrimer

The Raman (10–3500 cm −1) and infrared (150–3500 cm −1) spectra have been recorded for tris(4-oxibenzaldehyde)thiophosphate. This compound includes structural parts of elementoorganic dendrimers: a core and terminal aldehyde groups. The structural optimization and normal mode analysis are performed for elementoorganic dendrimer on the basis of the ab initio density functional theory. It is found that the dendrimer exist in a single stable conformation with planar C 6H 4 CH O fragments. Our calculations show that conformer with one trans and two gauche 4-oxibenzaldehyde groups is realized. All these observations suggest that steric congestion does not disturb the construction of dendrimers even for the highest generations, and that terminal groups are readily available for further reactions. Relying on DFT calculations a complete vibrational assignment is proposed for different parts of the studied dendrimers.

Advances in understanding bioactivity of chitosan and chitosan oligomers against selected wood-inhabiting fungi

Abstract Nitrous acid deaminative depolymerisation was used to prepare three chitosan oligomer (CO) mixtures from high-molecular weight chitosan. These mixtures of chitosan oligosaccharides were analysed by electrospray ionisation mass spectroscopy, potentiometric titration and gel permeation chromatography. A method based on potentiometric titration of the amino groups of the oligomers gave an average degree of polymerisation (DP) for the three preparations of 5 (CODP5), 9 (CODP9) and 14 (CODP14). Chitosan acetate and the chitosan oligomer mixtures were assayed against Leptographium procerum, Sphaeropsis sapinea and Trichoderma harzianum on nutrient media. Leptographium procerum and S. sapinea growth was prevented by chitosan acetate and chitosan oligomers at concentrations of 0.3–0.4% (w/v), whereas T. harzianum was able to overcome the fungistatic action of these compounds. The oligomer preparation CODP14 exhibited superior specific activity to both CODP5 and chitosan acetate, suggesting an optimum molecular weight for bioactivity. All oligomer preparations were more effective at pH 4 than at pH 6. This result, in combination with the inactivity of N-acetylated CODP14, indicated that amino group protonation was an important factor for fungistatic activity. The CODP14 preparation was reduced with sodium borohydride and fractionated by alkali precipitation and ion exchange chromatography. Bioassays of these fractions pointed towards DP and degree of deacetylation (DD) as key factors in chito-oligosaccharide bioactivity. Conversely, the terminal aldehyde groups generated by depolymerisation did not contribute to the activity observed.

Oxodienyl/Alkyne Coupling Reactions in Half-Open Ruthenocenes(II) and Related Species of Ru(IV)

A successful synthesis of Cp*Ru(η5-CH2CHCHCHO) (1) was obtained by chromatography on neutral deactivated alumina of Cp*Ru(1−4-η-CH2CHCHCHOSiMe3)Cl (2). The disproportionation reaction of 2 affords compounds 1 and Cp*Ru(1−3-η-endo-syn-CH2CHCHCHO)Cl2 (3). Reaction of compound 1 with diphenylacetylene affords compounds Cp*Ru[1−5-η-syn-CH(Ph)C(Ph)CHCHCH(CHO)] (6), Cp*Ru[1,4,5-η-C(Ph)C(Ph)CH2CHCH2]CO (7), Cp*Ru(1−3-η-CH2CHCHCHO)(η2-PhC⋮CPh) (8), and compounds with cyclic structures, such as Cp*Ru[1,6,7,10,11-η-CH(CH)4CCHC(Ph)CH(CH)2C(O)CH(C6H4)CH(Ph)] (9) and Cp*Ru[3,4,5-η-C(Ph)C(Ph)CHCHCHC(O)](η2-PhCHCHPh) (10). Reaction of compound 3 with diphenylacetylene shows the syn-aldehyde derivative 6, as well as the corresponding kinetic isomer 11, in which the terminal aldehyde group is in anti-position. Treatment of [Cp*RuCl2]2 with CH2CHCHCHOSiMe3 affords compound Cp*Ru[1−3-η-endo-syn-(Me)CHCHCH(OEt)]Cl2 (5). The Ru(IV) complex 5 reacts with diphenylacetylene to give the cyclic 1,2-diphenyl-3-methylcyclopentadieny...

Immobilization of Amine-Modified Oligonucleotides on Aldehyde-Terminated Alkanethiol Monolayers on Gold

Chemistry is described for the fabrication of DNA arrays on gold surfaces. Alkanethiols modified with terminal aldehyde groups are used to prepare a self-assembled monolayer (SAM). The aldehyde groups of the monolayer may be reacted with amine-modified oligonucleotides or other amine-bearing biomolecules to form a Schiff base, which may then be reduced to a stable secondary amine by treatment with sodium cyanoborohydride. The surface modifications and reactions are characterized by polarization modulation Fourier transform infrared reflection absorption spectroscopy (PM-FTIRRAS), and the accessibility, binding specificity, and stability of the DNA-modified surfaces are demonstrated in hybridization experiments.

The quantum topological electrostatic potential as a probe for functional group transferability.

The electrostatic potential can be used as an appropriate and convenient indicator of how transferable an atom or functional group is between two molecules. Quantum-chemical topology (QCT) is used to define the electron density of a molecular fragment and the electrostatic potential it generates. The potential generated on a grid by the terminal aldehyde group of the biomolecule retinal is compared with the corresponding aldehyde group in smaller molecules derived from retinal. The terminal amino group in the free amino acid lysine was treated in a similar fashion. Each molecule is geometry-optimized by an ab initio calculation at B3LYP/6-311G+(2d,p)//HF/6-31G(d) level. The amino group in lysine is very little influenced by any part of the molecule further than two C atoms away. However, the aldehyde group in retinal is influenced by molecular fragments six C atoms away. This dramatic disparity is ascribed to the difference in saturation in the carbon chains; retinal contains a conjugated hydrocarbon chain but lysine an aliphatic one.

Synthesis and Characterization of Chitosan Grafted Oligo(L‐lactic acid)

AbstractChitosan grafted oligo(L‐lactic acid) copolymers with different length of side chain were prepared through the reaction of terminal aldehyde group of oligo(L‐lactic acid) (OLLA) and amino groups of chitosan. The mean molecular mass of the grafting OLLA chain was ca. 600 ∼ 5 000. The graft copolymers are soluble in DMSO, DMF and acetic acid. The synthesis method and structure described here provide chitosan‐g‐OLLA copolymers with broad applicability.Structure of chitosan‐g‐oligo(L‐lactic acid).magnified imageStructure of chitosan‐g‐oligo(L‐lactic acid).

Organoiron Polyelectrolytes: Synthesis and Characterization of Cationic Cyclopentadienyliron Complexes of Polyarylether-Imines

The synthesis of an aromatic ether complex of cyclopentadienyliron containing two terminal aldehyde groups was achieved via metal-mediated nucleophilic aromatic substitution reactions. This dialdehyde monomer was subsequently reacted with a variety of aliphatic and aromatic diamines to produce the corresponding soluble cationic organoiron polyether-imines. These cationic organometallic polymers were characterized using IR, 1H, and 13C NMR, viscosity and thermogravimetric analysis. Viscosity measurements showed that these polymers exhibited polyelectrolyte effects in DMSO solutions. Thermogravimetric analysis showed that decoordination of the iron moieties occurred at about 300°C for polymers with aliphatic spacers in their backbones, while the cyclopentadienyliron moieties were cleaved from the polymers with aromatic spacers in their backbones at about 200°C. Photolytic demetallation of the organoiron polymers resulted in the removal of the pendent cyclopentadienyliron moieties and allowed for the isolation of their organic analogs. While the organoiron polymers were soluble in polar organic solvents, the corresponding organic polymers exhibited very limited solubilities or were insoluble. The organic polymers had glass transition temperatures between 101 and 120°C