The objective of the current in vitro study was to improve properties of a commonly used hydrogel for implant applications by incorporating novel self-assembled helical rosette nanotubes (HRNs). Since traditional methods (such as autografts and allografts) used to treat bone defects present various disadvantages (such as donor tissue shortage, extensive inflammation, possible disease transmission, and poor new bone growth), which may lead to implant failure, much effort has been devoted to creating a novel bone substitute that biomimics the nanoscale features of natural bone in order to improve bone growth. HRNs (formed by chemically immobilizing two DNA base pairs) are a novel type of soft nanomaterial that biomimics natural nanostructured components of bone (such as collagen) since they are 3.5 nm in diameter and self-assemble into a helical structure in aqueous solutions. Because HRNs undergo a phase transition from a liquid to a viscous gel when heated to slightly above body temperatures or when added directly to serum-supplemented or serum-free media at body temperatures, they may provide an exciting therapy to heal bone fractures in situ. In this study, HRN-K1 (HRNs functionalized with lysine amino acids) was embedded in and coated on a model hydrogel [specifically, poly(2-hydroxyethyl methacrylate) or pHEMA]. The results of this study showed, for the first time, enhanced osteoblast (bone-forming cell) adhesion on HRN-K1 embedded in and coated on hydrogels compared to hydrogels without HRN-K1. Moreover, the results showed that embedding HRN-K1 into hydrogels can greatly decrease the polymerization time of pHEMA (especially at low temperatures). The presence of lysine in HRN-K1/hydrogels was shown to be one, but not only, property of HRN-K1 that enhanced osteoblast adhesion. In summary, the present results demonstrated that HRNs can improve properties of one particular hydrogel (pHEMA) and, thus, should be further investigated as a bone-healing material.
Versatile, iterative synthetic protocols to form expanded [n]radialenes have been developed (n=3 and 4), which allow for a variety of groups to be placed around the periphery of the macrocyclic framework. The successful use of the Sonogashira cross-coupling reaction to complete the final ring closure demonstrates the ability of this reaction to tolerate significant ring strain while producing moderate to excellent product yields. The resulting radialenes show good stability under normal laboratory conditions in spite of their strained, cyclic structures. The physical and electronic characteristics of the macrocycles have been documented by UV-visible spectroscopy, electrochemical methods, and X-ray crystallography (four derivatives), and these studies provide insight into the properties of these compounds as a function of pendent substitution in terms of conjugation and donor/acceptor functionalization.
The reaction of various primary amines and 2,5-dihydroxy-1,4-dithiane in the presence of a catalytic amount of Mg(II) in distilled water provided a series of N-substituted 2,5-dithia-7-azabicyclo[2.2.1]heptanes. The adsorption profiles of the sulfur-containing heterocycles on gold surfaces have been explored by time-of-flight secondary ion mass spectrometry (TOF-SIMS), X-ray photoelectron spectroscopy (XPS), and electrochemistry. SIMS data indicated that these novel bicyclic sulfides interact with gold surfaces favorably, independent of the N-substitution, with minimal fragmentation. An XPS study revealed the three component core levels of S 2p with binding energies at 161, 162, and 163 eV, indicating a combination of the bound and unbound sulfur species. Using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), we found the efficient adsorption of heterocycles onto gold and the formation of densely packed films for alkyl and phenyl analogues. However, the adsorption and film packing properties were greatly compromised by an N-pyridyl substitution. The findings indicate that the surface behavior of N-substituted 2,5-dithia-7-azabicyclo[2.2.1]heptanes varies with respect to the N-substitution and the nature of the substituent, suggesting that the adsorption profiles and the film packing of bicyclic sulfides on gold surfaces are highly dependent on the binding interface and the molecular orientation.
This preliminary study reports on the synthesis of two new boron-capsaicin derivatives containing either a short or long chain aliphatic tail group using an iridium catalyzed hydroboration reaction with pinacolborane. The boronate ester groups reside on the terminal position of the tail group and are necessary for the bioactivity of these compounds. Indeed, both compounds showed considerable activity against two Gram-positive bacteria, including Vancomycin-resistant Enterococcus. Vancomycin is considered the last resort medication for the treatment of septicemia, and new antibacterial agents that can treat sepsis are of paramount importance. The more lipophilic boron compound with the longer aliphatic chain also showed antifungal activity against Saccharomyces cerevisiae.
ABSTRACT:The synthesis of donor-(D) and/or acceptor (A)-expanded [4]radialenes has been developed on the basis of readily available dibromoolefin (7), tetraethynylethene (10 and 20), and vinyl triflate (12) building blocks. The successful formation of D/A radialenes relies especially on (1) effective use of a series alkynyl protecting groups, (2) Sonogashira crosscoupling reactions, and (3) the development of ring closing reactions to form the desired macrocyclic products. The expanded [4]radialene products have been investigated by spectroscopic (UV−vis absorption and emission) and quantum chemical computational methods (density functional theory and time dependent DFT). The combined use of theory and experiment provides a basis to evaluate the extent of D/A interactions via the cross-conjugated radialene framework as well as an interpretation of the origin of D/A interactions at an orbital level. ■ INTRODUCTIONConjugated carbon-rich macrocycles are intriguing targets of study for both theoretical and experimental chemists because of their often symmetrical shape and aesthetically appealing structures. They are, however, useful molecules as well, with potential as the organic component for electronic, optical, and nonlinear optical applications.1−8 A specific subcategory of conjugated macrocycles are the [n]radialenes, which are cyclic, carbon-rich molecules with a general formula C 2n H 2n that contain n ring atoms and n exocyclic double bonds (1, Figure 1). "Expanded radialenes" are derivatives of radialenes that originate by formal insertion of an unsaturated spacer between each pair of exomethylene fragments of a radialene, giving rise to macrocycles such as 2 and 3 (Figure 1). 8−12 Work with expanded radialenes was pioneered by Diederich and co-workers 13−16 via the introduction of diacetylene moieties into the radialene framework to give derivatives with the general structure 3 17,18 as well as structurally related radiannulenes.19−27 More recently, expanded radialenes 2 composed of repeating enyne units have been realized and studied. 28−30The two-dimensionally (2D) conjugated structure of expanded [n]radialenes is rather special because it combines a number of linearly and cross-conjugated pathways placed on a nonbenzoid carbon framework.31−39 One key question concerning the properties of expanded [n]radialenes has been the role played by cross-conjugation 9,40,41 to the overall electronic makeup of these unique molecules. The influence of D−A or D/A interactions 42 via cross conjugation in acyclic systems has been explored by a number of groups. 9,10,43−46 To date, however, only a few examples of donor-or acceptor-expanded radialenes have been reported. 18,28 Finally, donor−acceptor-expanded radialenes remain unknown, and there have been no attempts to document cross-conjugated interactions in these derivatives using theory.Our group has recently reported a modular approach for the synthesis of perphenylated expanded [n]radialenes 29 and radiaannulenes. 22,29 This approach has been especially useful ...
Three 2-methyl-3-hydroxypyridinones, 1-methyl-, 1; 1-(4-methoxy)phenyl-, 2; and 1-(4-dimethylamino)phenyl-, 3, were discovered not to possess strong antioxidant properties contrary to literature reports. These pyridinones were not active chain-breaking antioxidants toward peroxyl radicals generated from styrene or methyl oleate initiated by azobis-2-methylpropylnitrile (AIBN) in solution compared to known phenolic antioxidants, 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMHC) or 2,6-di-tert-butyl-4-methoxyphenyl (DBHA). Pyridinone 2 exhibited weak antioxidant activity in cumene, kinh = 1.3 × 10(3) M(-1) s(-1), compared to 2,6-di-tert-butyl-4-methylphenol (BHT), kinh = 4.3 × 10(3) M(-1) s(-1). The pyridinones were not active antioxidants during lipid peroxidation initiated by azobis-2-amidinopropane·2HCl (ABAP) in aqueous-lipid dispersions of 0.50 M sodium dodecyl sulfate (SDS) micelles where 2 did not inhibit peroxidation of methyl oleate at pH 7.0 or 4.0, while BHT exhibited effective suppression of oxygen uptake. In addition, 2 did not exhibit any cooperative antioxidant effect in combination with Trolox during inhibited peroxidation of linoleic acid in micelles. Pyridinones were effective preventative antioxidants in aqueous-lipid dispersions against reactions initiated by heavy metal ions, notably copper; for example, 2 blocked peroxidation of linoleic acid initiated by Cu ions in SDS micelles. In particular, both 2 and 3 were active in preventing the rapid pro-oxidation effects, "spikes", of very rapid oxygen uptake when phenolic antioxidants PMHC or Trolox were added to peroxidations initiated by Cu(2+). A proposal is given to account for such pro-oxidant effects.
The objective of the current in vitro study was to create an injectable bone-like tissue engineering scaffold based on the novel self-assembled properties of helical rosette nanotubes (HRNs) in order to effectively improve bone growth at bone defect sites. HRNs with different functional groups can present unique surface chemistries which play a crucial role in improving osteoblast (bone forming cell) adhesion and subsequent functions. Since HRNs are very soft organic nanotubes, a hydrogel can strengthen such a 3D matrix. The preliminary results of this study show that HRNs have better cytocompatibility and osteoblast (bone forming cell) adhesion when mixed with hydrogels even at a very low HRN-K1 concentration of 0.001 mg/ml.
To date, although traditional autografts and allografts have been standard methods to treat bone fractures and defects, the formation of biocompatible and injectable scaffolds to induce new bone growth is still a promising method to repair bone defects considering their minimally invasive and osteoinductive features. In this study, a novel bone tissue engineering scaffold based on the self-assembled properties of helical rosette nanotubes (HRNs) and biocompatible hydrogels (specifically, poly(2-hydroxyethyl methacrylate)-pHEMA) was designed to fill bone fractures and repair bone defects. HRNs are a new class of organic nanotubes with a hollow core 11 Å in diameter, which originate from the self-assembly of DNA base pair building blocks (guanine-cytosine) in aqueous solutions. Since HRNs can significantly change their aggregation state and become more viscous based on heating or when added to serum free medium at body temperature, HRNs may provide an exciting therapy to heal bone fractures as injectable bone substitutes. In addition, biocompatible hydrogels were used in conjunction with HRNs in this study to strengthen the bone substitutes and also to serve as a potential drug releasing carrier to stimulate new bone growth at such fracture sites. Two types of HRNs, one with a lysine side chain and the other conjugated to 1% and 10% RGD (arginine-glycine-aspartic acid) peptides on HRNs, were prepared and dispersed into hydrogels. Due to their nanometric features and the helical architecture of HRNs which biomimic collagen, results showed that these HRN hydrogel composites can significantly improve osteoblast adhesion compared to hydrogel controls. Furthermore, 0.01 mg/ml HRNs with RGD embedded in and coated on hydrogels can also enhance osteoblast attachment compared to 0.01 mg/ml HRNs with lysine side chains embedded in and coated on hydrogels. Results showed an increasing trend of osteoblast adhesion on these scaffolds with more RGD groups (10%) on HRNs. In this manner, nanostructured HRN hydrogel composites provide a promising alternative to repair bone defects considering the flexibility in the design of HRNs and their exceptional cytocompatibilty properties.
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