Aldehyde Functional Groups Research Articles

2′-Oxoethyl Flavin Revisited

The present work investigates the possibility of using 2'-oxoethyl flavin (2) as a starting material for the construction of more complicated flavin-based molecules. 2'-Oxoethyl flavin (2), prepared by oxidative degradation of commercially available riboflavin 1, is however a rather untypical aldehyde. It prefers the hydrated gem-diol form 4 in aqueous solution. Ab initio electronic structure calculations, carried out at the level of Møller-Plesset perturbation theory of second order (MP2), predict the existence of an intramolecular hydrogen bond between one of the hydroxy groups of the diol and the N1 atom of the flavin skeleton. This result is supported by 1H NMR measurements which indicate an interaction between the hydroxy groups and the conjugated ring system. We postulate that this rather strong intramolecular hydrogen bond is the origin of the enhanced stability of the gem-diol over the aldehyde form 2. Synthetic applicability of 2'-oxoethyl flavin 2 is limited by low solubility in most organic solvents and sensitivity to basic conditions. The aldehyde functional group is surprisingly reluctant to nucleophilic attack, and several reactions quite typical for aldehydes failed. Nevertheless, reductive amination led to the expected secondary amine 7. Solubility of the molecule thus increased, and a new amino group was introduced.

Profiling the Enzymatic Properties and Inhibition of Human Complement Factor B

Human complement factor B is the crucial catalytic component of the C3 convertase enzyme that activates the alternative pathway of complement-mediated immunity. Although a serine protease in its own right, factor B circulates in human serum as an inactive zymogen and there is a crystal structure only for the inactive state of factor B and various fragments. To provide greater insight to the catalytic function and properties of factor B, we have used short para-nitroanilide derivatives of 4- to 15-residue peptides as substrates to profile the catalytic properties of factor B. Among factors found to influence catalytic activity of factor B was an unusual dependence on pH. Non-physiological alkaline conditions strongly promoted substrate cleavage by factor B, consistent with a pH-accessible conformation of the enzyme that may be critical for catalytic function. Small N-terminal extensions to conventional hexapeptide para-nitroanilide substrates significantly increased catalytic activity of factor B, which was more selective for its cleavage site than trypsin. The new chromogenic assay enabled optimization of catalysis conditions, the profiling of different substrate sequences, and the development of the first reversible and competitive substrate-based inhibitor of factor B. The inhibitor was also shown to prevent in vitro formation of C3a from C3 by factor B, by synthetic and by natural C3 convertase of the alternative complement activation pathway, and to block formation of membrane attack complex. The availability of a reversible substrate-based inhibitor that could stabilize the active conformation of factor B, in conjunction with a pH-promoted higher processing activity, may offer a new avenue to obtain crystal structures of factor B and C3 convertase in an active conformation.

Ozonation of polycyclic aromatic hydrocarbon in hexane and water: Identification of intermediates and pathway

The recalcitrant nature of pyrene and other polycyclic aromatic hydrocarbons (PAHs) lies in part in their low solubility in water, rendering them less susceptible to chemical and biological degradation. To overcome this remediation obstacle, this work investigates the use of a 2-stage ozonation process, first in nonpolar hexane phase then in polar aqueous phase, for the treatment of hydrophobic contaminants using pyrene as a model compound. The objectives of this research are to break down pyrene by using ozonation, identify the intermediates of pyrene, show a general degradation pathway of pyrene subject to ozonation and test the biodegradability of intermediates and byproducts of pyrene in the aqueous phase. The first stage briefly ozonates the contaminant at high concentration in organic solvent hexane, which facilitates very efficient conversion of the hydrophobic compounds into ring-opened polar intermediates containing alcohol, aldehyde, and acid functional groups.

Magnetic Resonance Contrast Agents from Viral Capsid Shells: A Comparison of Exterior and Interior Cargo Strategies

Two high-relaxivity nanoscale magnetic resonance contrast agents have been built using bacteriophage MS2 as a biomolecular scaffold. Protein capsid shells were functionalized on either the exterior or interior surface to display multiple copies of an aldehyde functional group. Subsequently, approximately 90 heteropodal bis(hydroxypyridonate)terephthalamide ligands were attached to these sites through oxime condensation reactions. Upon complexation with Gd3+, contrast agents with ionic relaxivities of up to 41.6 mM-1 s-1 (30 MHz, 25 degrees C) and total molecular relaxivities of up to 3900 mM-1 s-1 (30 MHz, 25 degrees C) were produced. Capsids sequestering the Gd-chelates on the interior surface (attached through tyrosine residues) not only provided higher relaxivities than their exterior functionalized counterparts (which relied on lysine modification) but also exhibited improved water solubility and capsid stability. The attachment functional cargo to the interior surface is envisioned to minimize its influences on biodistribution, yielding significant advantages for tissue targeting by additional groups attached to the capsid exterior.

Formation of the first injectable poly(vinyl alcohol) hydrogel by mixing of functional PVA precursors

AbstractIn this study we describe the development of an injectable, in situ chemical hydrogel forming system. The gelation occurs under neutral pH and at room temperature immediately upon mixing of the two aqueous poly (vinyl alcohol) components specifically derivatized through carbamate linkages with aldehyde (PVA‐AL) and hydrazide (PVA‐HY) functional groups, respectively. Aldehyde and hydrazide pendant groups were incorporated with a low degree of substitution (DS) into the PVA backbone to keep PVA structural homogeneity minimally altered. As a result, the hydrazone crosslinks are formed rapidly between aldehyde and hydrazide pendant groups when the correspondingly modified PVA components are brought in contact as water solutions. To assess in situ hydrazone crosslinks formation for in vitro cytocompatibility, murine neuroblastoma N2a cells were suspended in cell culture medium with the dissolved PVA‐HY prior to addition to the PVA‐AL aqueous solution. Thus, the cells were chemically encapsulated in a polymer network that was formed by mixing of the corresponding aqueous solutions of PVA functional precursors. Biochemical analysis revealed that cells survived chemical crosslinking and remained viable in the hydrogel for 4 days of culture. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007

Immobilization of oligoglycines on aldehyde-decorated surfaces and its influence on the orientations of liquid crystals

This paper reports an investigation of the immobilization of glycine (Gly), glycyl-glycine (Gly-Gly), and glycyl-glycyl-glycine (Gly-Gly-Gly) on silica substrates (colloidal silica, silicon wafer, and glass slides) decorated with aldehyde functional groups. It is found that the density of Gly or oligoglycines immobilized on the surface can be greatly enhanced by using higher ionic strength (∼1 M) and a reaction temperature of 50 °C. High ionic strength was used to screen the electrostatic repulsion caused by the negatively charged carboxylate groups of Gly or oligoglycines, while higher temperature was needed to increase the reaction rates. It is also found that when a thin layer of nematic liquid crystal 4-pentyl-4′-cyano-biphenyl (5CB) was supported on a Gly or oligoglycine-decorated surface, the orientation of 5CB changed from planar to homeotropic (perpendicular to the surface) over a period of 24 h. Furthermore, the switching time decreased when the surface density of oligoglycines was increased, and when the length of oligoglycines was increased by one or two Gly residues. The kinetic information provides a means to distinguish Gly, Gly-Gly, and Gly-Gly-Gly that only differ by a single Gly without using fluorescence or radioactive labeling. This method also has good spatial resolution over a large area that permits the detection of multiple oligoglycines patterned on the same surface.

Reversible Addition−Fragmentation Transfer Polymerization of a Novel Monomer Containing Both Aldehyde and Ferrocene Functional Groups

A new monomer, 2-formal-4-vinylphenyl ferrocenecarboxylate (FVFC), containing both aldehyde and ferrocene functional groups was designed and prepared by the reaction of ferrocenecarboxylic acid chloride with 2-hydroxy-5-vinylbenzaldehyde. The controlled radical polymerization of FVFC was achieved using 2,2‘-azobis(isobutyronitrile) (AIBN) as the initiator and 2-cyanopropyl-2-yl dithiobenzoate (CPDB) as the reversible addition−fragmentation chain transfer (RAFT) agent at 60 °C in tetrahydrofuran (THF). The polymerization nearly followed first-order kinetics, the number-average molecular weight of the obtained polymers increased almost in direct proportion to the monomer conversion, and the molecular weight distribution was narrow (polydispersity index < 1.2). The chain and terminal structures of the obtained polyFVFC were confirmed by 1H NMR and matrix-assisted laser desorption−ionization time-of-flight mass spectrometry analysis. The obtained polyFVFC can be employed as a macro-RAFT agent for styrene poly...

Influence of additives on the properties of Bis-GMA/Bis-GMA analog comonomers and corresponding copolymers

Objectives The purpose of this study was to evaluate the effect of two additives: propionaldehyde (aldehyde) and 2,3-butanedione (diketone) on the properties of Bis-GMA diluted with TEGDMA and the synthesized Bis-GMA analogs, propoxylated Bis-GMA (CH 3Bis-GMA) and propoxylated fluorinated Bis-GMA (CF 3Bis-GMA). Methods Nine experimental comonomers were prepared combining Bis-GMA and TEGDMA, CH 3Bis-GMA, CF 3Bis-GMA, with aldehyde (32 mol%) and diketone (32 mol%). Photopolymerization was effected by using Camphorquinone (0.2 wt%) and N, N-dimethyl- p-toluidine (0.2 wt%). Experimental comonomer viscosity (Brookfield viscometer), polymerization shrinkage (gravimetrically), degree of conversion (FT-IR) and contact angles (contact angle goniometer) were determined. Comonomer and copolymer T gs (DSC and Fox equation) were also evaluated. Data were analyzed by one-way ANOVA and Tukey test ( α = 0.05). Results Bis-GMA/CH 3Bis-GMA and Bis-GMA/CF 3Bis-GMA with additives exhibited lower viscosities ( p < 0.01). Inclusion of additives into the comonomer systems did not produce significant increase in polymerization shrinkage ( p > 0.05). A significant increase in degree of conversion was shown for Bis-GMA/TEGDMA and Bis-GMA/CH 3Bis-GMA with additives ( p < 0.01). Additives reduced contact angle and comonomer T g values, whereas the corresponding copolymers with additives showed an increase in T g. Significance Use of novel comonomer systems with the addition of aldehyde and diketone functional groups would improve dental resin composite properties.

Dendrimer‐Scaffold‐Based Electron‐Beam Patterning of Biomolecules

Microarrays have revolutionized the field of genomics and more recently proteomics and have proven to be an asset in high-throughput screening. As the demand for improved sensitivity and throughput of biomolecular assays increases, considerable research effort has been put into developing microelectronic and nanophotonic biosensors, which are presumably more sensitive than conventional fluorescencebased assays and have a faster response time. The lithographic technology for making the densely packed microelectronic devices in a high-throughput manner is already quite advanced and may be integrated to form biosensors. This is expected to increase the pace of research in early detection of disease biomarkers, discovering cell-signal transduction pathways, and in drug discovery. Denser arrays are also important for reducing reagent volume consumption and to improve sensitivity. Successful biomolecule patterning on sensor chip circuitry requires a number of important steps. First, selective immobilization of the probe and reduction in non-specific binding should be achieved for higher signal-tonoise ratios. Second, reduction in the sensor size reduces the background, enhancing the signal-to-noise ratio, and therefore biomolecule patterns on the same order as the sensors are desirable. Third, the biomolecule pattern should be aligned with the sensor circuitry, which becomes more difficult as sensor size decreases. Finally, a fabrication process should be formulated to ensure that the biomolecules are intact and functional, which is a challenge given the harsh microor nanofabrication processing steps. Here, we have demonstrated an electron-beam (e-beam)-based approach fulfilling the above requirements for patterning biological macromolecules that does not involve the use of resist, hence eliminating the exposure of these biomolecules to harsh resist-stripping processes that are normally employed to remove the resist. A non-biofouling poly(ethylene glycol) self-assembled monolayer (PEG-SAM) was selectively removed by e-beam and patterned with aldehyde-terminated polyamidoamine dendrimer (ald-PAMAM-SAM) in a layer-by-layer (LbL) manner to covalently immobilize the aminated oligonucleotide, which bind only to their complementary sequence targets and can be stripped and reprobed. The Generation-6 (G-6) PAMAM molecule, terminated with 256 primary amine groups and 6.7 nm in diameter, was used to increase the surface density of aldehyde functional groups to increase the oligonucleotide-immobilization efficiency. Current techniques for patterning biomolecules involve the use of polymer-based templates, which can be removed mechanically without the use of organic solvents after biomolecule immobilization. However, serious limitations exist in each case. Poly(dimethylsiloxane) (PDMS)-based soft-lithographic techniques cannot be used to create high-resolution patterns, as aligning the PDMS pattern with sub-micrometer features has been shown to work in a mix-and-match manner with an accuracy of only 2 lm. Although alignment is not an issue for biomolecule patterning based on polymer liftoff, as it is an integrated process, this method involves extra steps of deposition and etching a polymer film, which increases the complexity of the process. Challenges are also encountered as the size of the photolithographic patterns decrease due to the increase in line-edge roughness (LER) and the isotropic nature of oxygen plasma etch. Patterned gold has been used for creating protein patterns using thiolbased linkers, but gold surfaces cannot be tolerated in some biosensors as gold interferes with the optical signal or conductivity of the sensor. This technique also includes extra photolithographic and lift-off processing steps for patterning gold. Protein patterning using fluorescence-tagged proteins C O M M U N IC A IO N S

Flood pulse influences on terrestrial organic matter export from an agricultural watershed

Riverine export of terrestrial organic carbon (TOC) plays an important role in the global C cycle through influences on coastal productivity, sedimentary preservation, and CO2 efflux. In order to examine the influence of hydrologic variability and upland processes on TOC export from a midwestern agricultural watershed, we applied lignin phenol and stable carbon isotope analyses to assess quantity, source, and relative degradation state of TOC in soils, sediments, and size‐fractioned aquatic OC from stream water. Flood conditions exported 90 times more dissolved organic carbon (DOC) than baseflow owing to increases in both discharge and concentration, indicating mobilization of additional DOC pools. These observations are supported by increased TOC contributions to aquatic OC during flooding. Furthermore, stable carbon isotope values show that OC exported during flooding is enriched in C4‐derived C by up to 38% (for high molecular weight DOC) with respect to baseflow, indicating different TOC sources are mobilized dependant on hydrologic conditions. Lignin phenols isolated from the colloid size fraction show progressive increases in the ratio of carboxylic acid to aldehyde functional groups (a measure of relative degradation state) with distance downstream suggesting selective partitioning to mineral surfaces and/or degradation to this size fraction. This study shows that TOC quantity, source, and relative degradation state can change dependant on hydrologic conditions and in‐stream transport in a small agricultural watershed. Moreover, these results are important in showing variability in TOC source and chemistry exported from headwater systems that might otherwise not be detected in studies of larger rivers.

Complete Sequential Functionalization of Monopyrrolotetrathiafulvalenes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enhanced Proteolytic Activity of Covalently Bound Enzymes in Photopolymerized Sol Gel

Trypsin is covalently linked to a photopolymerized sol-gel monolith modified by incorporating poly(ethylene glycol) (PSG-PEG) for on-column digestion of N(alpha)-benzoyl-l-arginine ethyl ester (BAEE) and two peptides, neurotensin and insulin chain B. The coupling of the enzyme to the monolith is via room-temperature Schiff chemistry in which an alkoxysilane reagent (linker) with an aldehyde functional group links to an inactive amine on trypsin to form an imine bond. The proteolytic activity of the immobilized trypsin was measured by monitoring the formation of N alpha-benzoyl-L-arginine (BA), the digestion product of BAEE. The BA is separated from BAEE by capillary electrophoresis and detected downstream (18.5 cm from the microreactor) by absorption (254 nm). Using the Bradford assay, we determined that 97 ng of trypsin is bound to the 1-cm microreactor located at the entrance of capillary column. The bioactivity of the trypsin-PSG-PEG microreactor at 20 degrees C for the digestion of BAEE was found to be 2270 units/mg of immobilized trypsin. The bioactivity of trypsin bound to the capillary wall in the open segment upstream from the monolith was 332 units/mg of immobilized trypsin under the same conditions. In contrast, the activity of free trypsin could not be observed for the digestion of BAEE at 20 degrees C after 16 h of incubation time.

Backbone amide linker (BAL) strategy forNα-9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis of peptide aldehydes

A rapid and efficient strategy has been developed for the general synthesis of complex peptide aldehydes. N(alpha)-Benzyloxycarbonylamino acids were converted to protected aldehyde building blocks for solid-phase synthesis in four steps and moderate overall yields. The aldehydes were protected as 1,3-dioxolanes except for one case where a dimethyl acetal was used. These protected amino aldehyde monomers were then incorporated onto 5-[(2 or 4)-formyl-3,5-dimethoxyphenoxy]butyryl-resin (BAL-PEG-PS) by reductive amination, following which the penultimate residue was introduced by HATU-mediated acylation. The resultant resin-bound dipeptide unit, anchored by a backbone amide linkage (BAL), was extended further by routine Fmoc chemistry procedures. Several model peptide aldehydes were prepared in good yields and purities. Some epimerization of the C-terminal residue occurred (10% to 25%), due to the intrinsic stereolability conferred by the aldehyde functional group, rather than any drawbacks to the synthesis procedure.

Complete Sequential Functionalization of Monopyrrolotetrathiafulvalenes

Introduction of aldehyde and ketone functional groups into the α-positions of monopyrrolotetrathiafulvalene provides a novel method for a stepwise and selective penta-functionalization of monopyrrolotetrathiafulvalene derivatives.

Novel Routes for the Generation of Structurally Diverse Labdane Diterpenes from Andrographolide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chemoselective synthesis of multiple epoxy-bridged tetrahydropyranone ring systems

Bis- as well as tris-tetrahydropyranone ring systems were obtained via multiple tandem cyclization–1,3-dipolar cycloaddition reactions of α-diazo ketones with ketone as well as aldehyde functional groups in a chemoselective manner.

A Practical Synthesis of 3,4-Dimethoxy-o-toluic Acid

A streamlined, telescoped process has been developed for the preparation of 3,4-dimethoxy-o-toluic acid, starting with economical and readily available 2,3-dimethoxybenzaldehyde. Catalytic reduction of the aldehyde functional group generated dimethoxytoluene, which was brominated in situ. The resultant aryl bromide was isolated, converted into a Grignard reagent, and transformed into a carboxylic acid with dry ice. The process was demonstrated on a pilot-plant scale.

Novel routes for the generation of structurally diverse labdane diterpenes from andrographolide

Andrographolide 1 , the major constituent of the Indian medicinal plant Andrographis paniculata (Acanthaceae) was converted into the key intermediate 4 by selective oxidative degradation of the C-12,13 olefin bond. The aldehyde functional group present in 4 has been utilized for synthesizing a number of structurally diverse labdane diterpenes. Synthesis and in vitro cytotoxic activity results of the compounds prepared are discussed.

Attachment of hyaluronan to metallic surfaces

Metal implants are in general not compatible with the tissues of the human body, and in particular, blood exhibits a severe hemostatic response. Herein we present results of a technique to mask the surface of metals with a natural biopolymer, hyaluronan (HA). HA has minimal adverse interactions with blood and other tissues, but attachment of bioactive peptides can promote specific biological interactions. In this study, stainless steel was cleaned and then surface-modified by covalent attachment of an epoxy silane. The epoxy was subsequently converted to an aldehyde functional group and reacted with hyaluronan through an adipic dihydrazide linkage, thus covalently immobilizing the HA onto the steel surface. Fluorescent labeling of the HA showed that the surface had a fairly uniform covering of HA. When human platelet rich plasma was placed on the HA-coated surface, there was no observable adhesion of platelets. HA derivatized with a peptide containing the RGD peptide sequence was also bound to the stainless steel. The RGD-containing peptide was bioactive as exemplified by the attachment and spreading of platelets on this surface. Furthermore, when the RGD peptide was replaced with the nonsense RDG sequence, minimal adhesion of platelets was observed. This type of controlled biological activity on a metal surface has potential for modulating cell growth and cellular interactions with metallic implants, such as vascular stents, orthopedic implants, heart valve cages, and more.

Crystal structure of the Escherichia coli Tas protein, an NADP(H)-dependent aldo-keto reductase.

Crystal structure of the Escherichia coli Tas protein, an NADP(H)-dependent aldo-keto reductase.