Terminal Aldehyde Research Articles

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.

Alternative farnesoid structures induce different conformational outcomes upon the Drosophila ortholog of the retinoid X receptor, ultraspiracle

In view of recent studies that the ligand-binding pocket of the Drosophila melanogaster nuclear hormone receptor, ultraspiracle (dUSP), is a necessary component of dUSP-dependent transcriptional activation by methyl epoxyfarnesoate, we have assessed qualitative differences in the effect of farnesoid and dodecanoid compounds on receptor conformation and transcriptional activation. Farnesoids possessing terminal alcohol, aldehyde, acid, ester and/or epoxide moieties induced different changes in the local environment of the ligand-binding pocket, as monitored by the change each induced in the fluorescence of the two tryptophan residues existing in dUSP (that are situated 10 residues apart on the α-helix 5 that forms one lining of ligand-binding pocket). Similarly, each compound differed in the extent that it promoted an increase in anisotropy (dimerization state) of the receptor. Dodecanoid derivatives were much weaker in causing such effects. Methyl expoxyfarnesoate (insect juvenile hormone III) exhibited the greatest biological activity to increase transcription of a DR12JHECore reporter construct in transfected Sf9 cells, even though it did not exert the most suppression of USP fluorescence nor exert the greatest increase in USP anisotropy. In a comparison of farnesoid derivatives possessing the three side branches either as all methyl groups (JH III), or one of the side branches as ethyl (JH II), or two of the side branches as ethyl (JH I), the JH III and JH I were more similar to each other in the fluorescence suppression and in vivo morphogenetic activity than either was to JH II, evidencing that dUSP does not sense JH II as a structural ‘intermediate’ between JH III and JH I. Ligand-binding domains of vertebrate retinoid X receptors respond to agonists by repositioning α-helix 12 to the edge of a hydrophobic groove, and there with the groove jointly forms a coactivator binding surface. When α-helix 12 in dUSP was mutated to place two signaling tryptophan residues its C-terminus, fluorescence signaling indicated that upon dUSP binding of methyl epoxyfarnesoate, the α-helix 12 was repositioned differently than what occurred upon binding of non-JH farnesoids. These leads on alternative ligand-induced conformations that dUSP can adopt provide a foundation for commercial development of synthetic molecules that induce specific dUSP conformations, and for identification of in vivo conditions under which endogenous molecules may exert these conformational outcomes to this receptor.

Fourier-transform infrared and Raman difference spectroscopy studies of the phosphorus-containing dendrimers

FT IR and Raman spectra of 12 generations of the phosphorus-containing starburst dendrimers containing PS and PO bonds with terminal aldehyde and PCl groups were compared. The influence of the encirclement on the band frequencies and intensity is studied and due to the predictable, controlled and reproducible structure of the dendrimers the information usually inaccessible is obtained. Bands in the IR difference ( G 2′(PO) G 2′(PS)) spectra have characteristic EPR-like form. The strong band at 1600 cm −1 show marked changes of the optical density in dependence of the aldehyde (CHO) or azomethyne (CHN) substituents in the aromatic ring. The analysis of difference spectra enables one to assign the characteristic bands ν(PS) and ν(PO) for the bonds in the core, in the repeating unit and in the terminal groups of the dendrimers. This assignment is supported by the calculation of the absorption curves of the different fragments of dendrimer with the force constants and electro-optical parameters. The IR and Raman spectra of dendrimers are depended on the ratio of number terminal groups to a number of repeating units, which in its turn is strictly determined by the generation number. Thus, the marked differences in the vibrational spectra of the first successive generations aspire to zero for the higher ones. The rather rigid repeated units with little conformational flexibility define the perfect microstructure of the studied phosphorus-containing dendrimers up to the eleventh generation.

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).

Methods for the Synthesis of Oligonucleotides Containing Reactive Electrophilic Groups

AbstractFor Abstract see ChemInform Abstract in Full Text.

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

N-terminal site-specific mono-PEGylation of epidermal growth factor.

N-terminal site-specific mono-PEGylation of recombinant human epidermal growth factor (EGF) was accomplished using polyethyleneglycol (PEG) derivatives (Mw = 2000 and 5000) through a reactive terminal aldehyde group. The site-specific PEG conjugation was conducted ata slightly acidic pH condition (pH 5.5). The mono-PEGylation was targeted to an alpha-amine group at the N-terminal end of EGF to minimize reduction of biologic activity. Tryptic digestion mapping and MALDI-TOF MS techniques were applied to show the occurrence of mono-PEGylation at the N-terminus of EGF. The site-specific mono-PEGylated EGF, when compared with native EGF, fully retained its in vitro biologic activities such a cell proliferation and intracellular signal transduction. This revealed that although a synthetic polymer of a PEG was covalently conjugated to EGF, the internalized complex of PEGylated EGF-receptor within cells did not hamper the intracellular signal transduction events. The PEGylated EGF also exhibited a prolonged circulation in blood stream in vivo and markedly enhanced physical stability whe incubated with tissue homogenate. N-terminally mono-PEGylated EGF shows increased physical stability while retaining its biologic activity.

Silicone elastomer surface functionalized with primary amines and subsequently coupled with heparin.

Primary amines covalently bonded to the surface of poly(dimethylsiloxane) were obtained by hydrosilylation grafting of aminopropyl vinyl ether to Si-H groups formed during argon plasma treatment. The amine groups were derivatized using pentafluorobenzaldehyde and characterized by X-ray photoelectron spectroscopy. The graft yield was about 3% grafted molecules within the depth of the analysis. The terminal aldehyde groups of diazotized heparin was also coupled to the primary amines. This led to a silicone elastomer with covalently bonded heparin which was expected to be hydrolytically stable. This method of bonding primary amines to the surface of silicone elastomers and the subsequent coupling of aldehyde-containing molecules is a promising way of obtaining novel biomaterials.

The vibrational analysis of the starting “monomer” and first generation of the starburst elementoorganic dendrimer

The Raman (10–3500 cm −1) and infrared (150–3500 cm −1) spectra have been recorded for tris(4-oxibenzaldehyde)thiophosphate and tris(4- N′-dichloro(thio)phosphonyl)- N′-methyl-diazobenzene)monothiophosphate. These compounds include the main structural parts of the starburst elementoorganic dendrimers: the core, the repeated units, the terminal aldehyde and PCl groups. Relying on group frequencies and intensities of the infrared and Raman bands, a complete vibrational assignment is proposed for different parts of the studied dendrimers. The assignment is supported by the infrared spectra calculation, which was carried out utilizing force field and electro-optical parameters (EOP). All of these results were used for the interpretation of the experimental Raman and infrared spectra of dendrimers. The heat capacities of the eleven generations of the dendrimers were estimated based on the calculated values of the statistical sums.

Photocrosslinkable polymers bearing pendant conjugated heterocyclic chromophores

This article describes the synthesis of furan- and thiophene-based chromophores bearing a terminal aldehyde function which was used to append them to polyvinyl alcohol (PVA) and thus obtain photosensitive polymers. Because of their conjugated structure, the chromophores absorbed in the near-UV domain and only displayed two photochemical transformation, viz. a trans– cis isomerisation and a bimolecular cyclodimerisation. The latter reaction was exploited to induce the crosslinking of the modified PVAs. The application of these materials as photosensitive resins for lithographic plates is the practical issue of the present investigation.

Reaction of Carbon Monoxide with Living PP Prepared with a Cp2ZrMe2/B(C6F5)3 Catalyst System

The reaction between carbon monoxide (CO) and the living Zr-poly(propylene) (Zr-PP) bond, which was prepared with Cp2ZrMe2/B(C6F5)3/AlOct3 catalyst system at –78°C, was investigated. The reaction products were analyzed by means of IR, 1H-NMR and GPC. Under the reaction conducted at –78°C, it could be found that CO was quantitatively incorporated into the Zr-PP bond to generate a terminal aldehyde group. And when the reaction was started at –78°C and gradually warmed up to room temperature, a ketone carbonyl in the polymer chain was formed.

Synthesis and structure–activity relationships of potent and orally active sulfonamide ETB selective antagonists

The synthesis and structure–activity relationships of a series of N-pyrimidinyl benzenesulfonamides as ETB selective antagonists are described. N-Isoxazolyl benzenesulfonamide 1a, previously reported,1 was selected as a lead compound, and isosteric replacement of the isoxazole ring of 1a with a pyrimidine ring led to the discovery of the highly potent ETB selective antagonist 6e with oral bioavailability. Modification of the terminal aldehyde group at the 6-position of the pyrimidine ring was investigated, and malonate 15b and acylhydrazone 16f were found to be equipotent to aldehyde 6e. Compound 6e showed ETB antagonistic activity on in vivo evaluation.

Effects of Polyene Chain Length and Acceptor Substituents on the Stability of Carotenoid Radical Cations

The stability of radical cations of three series of carotenoids substituted with terminal ester, aldehyde, and cyano groups and with different numbers of backbone double bonds was studied by electrochemical and optical methods. The ethyl esters are 8‘-apo-β-caroten-8‘-oate (I), 6‘-apo-β-caroten-6‘-oate (II), and 4‘-apo-β-caroten-4‘-oate (III); the aldehydes are 8‘-apo-β-caroten-8‘-al (IV), 6‘-apo-β-caroten-6‘-al (V), and 4‘-apo-β-caroten-4‘-al (VI); and the cyano compounds are 8‘-apo-β-caroten-8‘-nitrile (VII), 6‘-apo-β-caroten-6‘-nitrile (VIII), and 4‘-apo-β-caroten-4‘-nitrile (IX). Cyclic voltammetry (CV) and Osteryoung square wave voltammetry (OSWV) results indicate that the stability of carotenoid radical cations depends on the number of conjugated chain double bonds. For the esters, the longer the olefin chain, the more unstable the radical cations. In contrast, for the aldehydes and the nitriles, the stability of the radical cations is similar or varies slightly with backbone chain length. The half-...

Synthesis of a quaternary ammonium derivative of chito-oligosaccharide as antimicrobial agent for cellulosic fibers

A derivative of chito-oligosaccharide (COS), N-(2-hydroxyl)propyl-3-trimethyl ammonium chito-oligosaccharide chloride (HTACC), was synthesized using a reaction of glycidyltrimethylammonium chloride (GTMAC) and COS prepared by depolymerization of a fully deacetylated chitosan. COS and HTACC were applied to the cotton fabrics with a pad-dry-cure process using the reaction between the hydroxyl group of cellulose and terminal aldehyde group in COS and HTACC. Their minimum inhibition concentration (MIC) was evaluated, and the antimicrobial activity and durability to laundering of cotton fabrics treated with them were compared. The complete substitution of NH2 groups in COS with GTMAC was obtained at a 4 : 1 mol ratio of GTMAC to NH2 in 18 h at 80°C under the presence of acetic acid. MIC values of the 1.04 DS of HTACC and COS were 50 and 400 μg/mL, respectively. A cotton fabric treated with 0.2% of HTACC and 1.8% of COS exhibited 100% reduction of bacteria. At the 50th laundering cycle, 0.3% of HTACC and 2.4% of COS indicated 100% bacterial reduction. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 2009–2015, 2000

X-ray structure of a trimeric 5,5'-biaryl/erythro-beta-O-4-ether lignin model: evidence for through-space weak interactions.

The crystal structure of a trimeric lignin model 1 presenting the characteristic pattern of biphenyl (5,5') and aryl-alkyl-ether (beta-O-4) linkages has been determined. The crystal system is triclinic and the crystallographic unit cell consists of two monomeric molecules. These results are compared with crystal data from the literature of simple models of the 5,5' and beta-O-4 structure type. The availability of a terminal aldehyde function on the model affords some interesting intermolecular interactions by weak hydrogen bonding which controls the conformation of the molecule and the aromatic ring orientation in particular; an unexpected cisoïd conformation of the biaryl unit is observed based on the 64.4 degrees value found for the torsion angle between the two 5,5' aromatic rings.

New cyclization reaction at the amino terminus of peptides and proteins.

Mild oxidation with periodate of the 1-amino-2-ol moiety of N-terminal seryl or threonyl peptides and proteins leads to a terminal aldehyde function O=CH-CO- which usually may be exploited for bioconjugate formation (e.g., via oximation with an O-alkyl hydroxylamine). We report that, when followed by a prolyl residue, the O=CH-CO- group can undergo a rapid cyclization and dehydration reaction through nucleophilic attack by the amide nitrogen of the third amino acid residue of the chain. We have characterized the resulting heterocycle, which is stable in aqueous acid, by mass spectrometry and NMR. Quantitative oximation can nevertheless be achieved in such cases by performing a one-pot oxidation-oximation without isolation of the intermediate aldehyde, as is demonstrated with cholera toxin B subunit.

Preparing Chito-Oligosaccharides as Antimicrobial Agents for Cotton

Cotton fabric with good antimicrobial activity and durability to washing is obtained by using chito-oligosaccharides without the need for a binding chemical as a crosslinker. The fully deacetylated chitosan is depolymerized into chito-oligosaccharide using sodium nitrite. The average degree of polymerization (DP) of chito-oligosaccharide is determined by color imetric titration of a terminal aldehyde group of chito-oligosaccharide. In a pad-dry-cure process, two different chito-oligosaccharides (DP = 3 and 10) are applied to cotton fabric using the chemical reactivity of the terminal aldehyde group. The antimicrobial activity and durability to washing of the treated cotton are evaluated. The results show that at the fiftieth wash cycle, the cotton fabrics treated with 2.4% chito-oligosaccharide are able to maintain 95% (for a DP of 3) and 100% (for a DP of 10) bacterial reductions.

Oligo-2,6-naphthylenevinylenes – New Building Blocks for the Preparation of Photoluminescent Polymeric Materials

Synthetic strategies towards appropriate symmetric and unsymmetric functionalization of the naphthalene ring are presented. By means of Knoevenagel and Wittig condensation reactions new fluorescent, differently functionalized oligo(2,6-naphthylenevinylene)s have been synthesized, the presence of terminal aldehyde or bromine substitution opening the way to the incorporation of the fluorescent trimers in a variety of polymeric materials. The effect of substituting the phenylene ring by the more bulky dialkoxynaphthalene system in arylenevinylene-type materials is studied from the structural point of view and the possibility to tune the emission color and the electron affinity through the introduction of naphthylenevinylene and cyano-substituted naphthylenevinylene units is also investigated.

Allylmalonamide as a bivalent linker: synthesis of biantennary GM3-saccharide--keyhole limpet hemocyanin glycoconjugate and the immune response in mice.

A biantennary GM3-saccharide (sialyllactoside) derivative (4) was constructed using allylmalonic acid as a bivalent linker, both carboxylic acids of which were condensed with 3-aminopropyl lactoside (2) prior to enzymatic sialylation with a fusion enzyme. While ozonolysis of its allyl group generated a saccharide having a terminal aldehyde (6), we were unable to couple 6 directly to protein by reductive amination. However, extension of the spacer by means of introducing a maleimide group to 6 through its aldehyde group to give 7 enabled the latter to be successfully coupled to thiolated proteins. The average ratios of saccharide to protein were observed to be 35 in KLH conjugate (13) and 9-12 in HSA conjugates (14 and 15). The antisera obtained by immunizing mice with the biantennary sialyllactoside-KLH conjugate (13) together with MPL adjuvant were analyzed by ELISA. Using several structurally related saccharide-HSA conjugates as screening antigens, it was concluded that anti-sialyllactoside antibodies, both IgG and IgM, were effectively raised. This was further supported by competitive inhibition experiments using lactoside (1), sialyllactoside (8) and biantennary sialyllactoside (4) as inhibitors.