Peripheral Functional Groups Research Articles

Effects of the central metal on stretching vibrational bands of the peripheral carbonyl moieties in formylated chlorophyll derivatives studied by Fourier-transform infrared spectroscopy

The vibrational properties of metal complexes of monoformylated and diformylated chlorophyll derivatives were compared with those of the corresponding free-base chlorins to unravel the effects of the central metal on the carbonyl stretching vibration modes of the peripheral oxygen functional groups in the chlorin macrocycle by means of FTIR spectroscopy. The 3- C = O stretching vibrational bands of a 3-formyl group were shifted to lower wavenumbers by insertion of Zn and Cu into the center of the 3-formyl free-base chlorin. In contrast, the 7- and 8- C = O stretching vibrational bands of the formyl groups linked to the B-ring of the chlorin macrocycle were barely shifted even if 7- and 8-formyl free-base chlorins were metalated. The down-shifts of the 3- C = O and few shifts of the 7-/8- C = O vibrational stretching bands were in line with the results of DFT calculations. The difference in the effects of the central metal on the vibrational properties between the formyl group in the A-ring and those in the B-ring is ascribable to the different conjugation manners with the adjacent π-system: the 3-formyl group was connected to the chlorin 18π-system, whereas the 7-/8-formyl groups were conjugated to the rather isolated C 7– C 8 double bond. The 13- C = O stretching vibrational bands were shifted to lower wavenumbers by metalation. These down-shifts can also be rationalized by invoking the conjugation of the 13-keto group with the chlorin 18π-system.

Polyamidoamine dendrimer and oleic acid-functionalized graphene as biocompatible and efficient gene delivery vectors.

Functionalized graphene has good potential in biomedical applications. To address a better and multiplex design of graphene-based gene vectors, the graphene-oleate-polyamidoamine (PAMAM) dendrimer hybrids were synthesized by the oleic acid adsorption and covalent linkage of PAMAM dendrimers. The micromorphology, electrical charge property, and amount of free amine groups of the graphene-oleate-PAMAM hybrids were characterized, and the peripheral functional groups were identified. The PAMAM dendrimers could be tethered onto graphene surface in high density. The graphene-oleate-PAMAM hybrids exhibit relatively good dispersity and stability in aqueous solutions. To evaluate the potential application of the hybrids in gene delivery vectors, cytotoxicity to HeLa and MG-63 cells and gene (plasmid DNA of enhanced green fluorescent protein) transfection capacity of the hybrids were investigated in detail. The graphene-oleate-PAMAM hybrids show mammalian cell type- and dose-dependent in vitro cytotoxicity. Under the optimal condition, the hybrids possess good biocompatibility and gene transfection capacity. The surface modification of graphene with oleic acid and PAMAM improves the gene transfection efficiency 13 times in contrast to the ultrasonicated graphene. Moreover, the hybrids show better transfection efficiency than the graphene oxide-PAMAM without the oleic acid modification.

The discovery of potent nonstructural protein 5A (NS5A) inhibitors with a unique resistance profile-Part 2.

In ongoing studies towards novel hepatitis C virus (HCV) therapeutics, inhibitors of nonstructural protein 5A (NS5A) were evaluated. Specifically, starting from previously reported lead compounds, peripheral substitution patterns of a series of biaryl-linked pyrrolidine NS5A replication complex inhibitors were probed and structure-activity relationships were elucidated. Using molecular modelling and a supercritical fluid chromatographic (SFC) technique, intramolecular H-bonding and peripheral functional group topology were evaluated as key determinants of activity and membrane permeability. The novel compounds exhibited retained potency as compared with the lead compounds, and also showed promising results against a panel of resistance viruses. Together, the results of the study take us a step closer towards understanding the potency of daclatasvir, a clinical candidate upon which the compounds were based, and to designing improved analogues as second-generation antiviral agents targeting NS5A.

Complexation of mercury(II) ions with humic acids in tundra soils

The interaction mechanisms of mercury(II) ions with preparations of humic acids (HAs) isolated from organic horizons of surface-gleyed soils (Haplic Stagnosol (Gelic, Siltic)) of shrub tundra and hydromorphic peat gley soils (Histic Cryosol (Reductaquic, Siltic)) of moss-lichen tundra have been studied. The particular features of the interactions between the mercury(II) ions and the HAs are related to the molecular structure of the HAs, the mercury concentration range, and the environmental parameters. The fixation of mercury(II) ions into stable coordination compounds is most efficient in the pH range of 2.5–3.5. At the element concentrations below 0.50 μmol/dm3, the main complexing sites of HAs are their peripheral aminoacid functional groups. Pyrocatechol, salicylate, and phenolic groups from the nuclear moiety of molecules interact in the concentration range of 0.0005–0.50 mmol/dm3; the physical sorption of mercury hydroxo complexes by the surface of HAs is the main process occurring in the system.

From Disilene (SiSi) to Phosphasilene (SiP) and Phosphacumulene (PCN)

The generation of heavier double-bond systems without by- or side-product formation is of considerable importance for their application in synthesis. Peripheral functional groups in such alkene homologues are promising in this regard owing to their inherent mobility. Depending on the steric demand of the N-alkyl substituent R, the reaction of disilenide Ar2Si=Si(Ar)Li (Ar = 2,4,6-iPr3C6H2) with ClP(NR2)2 either affords the phosphinodisilene Ar2 Si=Si(Ar)P(NR2)2 (for R = iPr) or P-amino functionalized phosphasilenes Ar2(R2N)Si=Si(Ar)=P(NR2) (for R = Et, Me) by 1,3-migration of one of the amino groups. In case of R = Me, upon addition of one equivalent of tert-butylisonitrile a second amino group shift occurs to yield the 1-aza-3-phosphaallene Ar2(R2N)Si=Si(NR2)(Ar)-P=C=NtBu with pronounced ylidic character. All new compounds were fully characterized by multinuclear NMR spectroscopy as well as single-crystal X-ray diffraction and DFT calculations in selected cases.

Efficient synthesis of small-sized phosphonated dendrons: potential organic coatings of iron oxide nanoparticles

We report herein the synthesis of biocompatible small-sized phosphonated monomers and dendrons used as functional coatings of metal oxide nanoparticles, more specifically superparamagnetic iron oxides (SPIOs) for magnetic resonance imaging (MRI) and therapy through hyperthermia. The molecules were engineered to modulate their size, their hydrophilic and/or biocompatible character (poly(amido)amine versus oligoethyleneglycol), the number of anchoring phosphonate groups (monophosphonate versus phosphonic tweezers) and the number of peripheral functional groups for further grafting of dyes or specific vectors. Such a library of hydrophilic phosphonic acids opens new possibilities for the investigation of dendronized nanohybrids as theranostics.

Spherosilicates with peripheral malonic acid and vinyl end groups

Two novel spherosilicates comprised of an octahedral Si8O12 core, [Si8O12]-(OSiMe2CH2CH2CH2CH(COOH)2)8 and [Si8O12]-(OSiMe2CH2CH2CH2CH(COOSi(CH=CH2)3)2)8, were synthesized from [Si8O12]-(OSiMe2H)8. These new structures have high densities of peripheral functional groups, and the second structure also possesses silyl ester bonds that are easily cleavable under mild conditions. These functionalities enable these structures to be modified further and to have many potential applications. We demonstrated one by cross-linking the vinyl-terminated spherosilicate to form nanospheres with a narrow size distribution and utilizing the hydrophilic interior to accommodate a Pd salt in a toluene solution.

On the Formation and Electropolymerization of a Star Copolymer With Peripheral Carbazoles

AbstractUtilizing a hyperbranched cored ring‐opening polymerization of caprolactone, carbazole peripheral groups are extended to afford electropolymerizable star‐like copolymers. Different arm lengths are obtained on the basis of different degrees of polymerization from the polyethyleneimine core. This is confirmed by NMR and Fourier transform IR (FTIR) spectroscopy, size‐exclusion chromatography (SEC), and quantitative spectral characterization. Atomic force microscopy (AFM) imaging shows two distinct particle aggregation characteristics, before and after functionalization with carbazole groups. Cyclic voltammetry verifies the electrochemical cross‐linking properties. The results indicate that the conformational freedom of the electroactive peripheral functional groups can be controlled. Moreover, an interesting “loop effect” together with solid‐state polymerization is observed.

Theoretical Investigation on the Electron and Energy Transfer between Peripheral Carrier Transport Groups and Central Chromophores in Electroluminescent Materials

AbstractThe molecular materials with structures of luminescent core and peripheral carrier groups (e.g. carbazoles), have exhibited high‐performance in organic light‐emitting diodes (OLEDs). Present work is to understand the basic process of electronic and energy exchange between the peripheral functional groups and the central core through quantum chemical analysis. As an example, 4,7‐bis(9,9‐bis(6‐(9H‐carbazol‐9‐yl)hexyl)‐9H‐fluoren‐2‐yl)benzo[c]‐[1,2,5]thiadiazole (TCBzC) is investigated in regards to optoelectronic properties using density functional theory (DFT). The results suggest that the forbidden transition from peripheral carbazole to the central chromophore core makes for separated electrical and optical properties, and high performance electroluminescence (EL) is mainly attributed to the energy‐transfer from carbazoles to the fluorene derivative core

Synthetic macrocyclic receptors in chiral analysis and separation

Chiral synthetic macrocyclic receptors that can achieve chiral discrimination by NMR spectroscopy and/or chiral separation by HPLC are overviewed. Synthetic macrocycles introduced here include crown ethers, calixarenes/calixresorcinarenes/calixpyrroles, macrocyclic amides/amines, and porphyrins. These macrocyclic frameworks are advantageous because intermolecular interactions can take place effectively, such as the ion–dipole interactions in crown ethers, the CH/π and π–π interactions in calixarenes, hydrogen bonding and salt formation in macrocyclic amides and amines, and π–π stacking and metal coordination in porphyrins. Additional functional groups on the periphery of the macrocyclic platforms not only make the whole molecule chiral but also act as the interaction sites. Chiral macrocyclic receptors can show a high degree of chiral recognition/discrimination by using the peripheral functional groups as well as the macrocyclic skeletons (preorganization). Both hosts and guests are shown in the figures to quickly overview the molecular recognition scope of synthetic macrocyclic receptors in chiral analysis and separation.

Dendronized iron oxide nanoparticles for multimodal imaging

The synthesis of small-size dendrons and their grafting at the surface of iron oxide nanoparticles were achieved with the double objective to obtain a good colloidal stability with a mean hydrodynamic diameter smaller than 100 nm and to ensure the possibility of tuning the organic coating characteristics including morphology, functionalities, physico-chemical properties, grafting of fluorescent or targeting molecules. Magnetic resonance and fluorescence imaging are then demonstrated to be simultaneously possible using such versatile superparamagnetic iron oxide nanocrystals covered by a dendritic shell displaying either carboxylate or ammonium groups at their periphery which could be further labelled with a fluorescent dye. The grafting conditions of these functionalized dendrons at the surface of SPIO NPs synthesized by co-precipitation have been optimized as a function of the nature of the peripheral functional group. The colloidal stability has been investigated in water and osmolar media, and in vitro and in vivo MRI and optical imaging measurements have been performed showing encouraging biodistribution.

POLY(L-GLUTAMIC ACID) DENDRON BASED pH SENSITIVE DRUG CARRIER WITH MAGNETIC NANOPARTICLE CORE

Recent advances on targeted drug delivery systems which interact with intracellular components or events such as pH change have been an exciting focus for biomaterials scientists.In present work,poly(L-glutamic acid) peptide dendron was synthesized,and dopamine was immobilized on it as the ligand to substitute the oleic acid on the surface of hydrophobic Fe3O4 magnetic nanoparticles via ligand exchange.The anticancer drug doxorubicin(DOX) was conjugated to the peripheral functional groups of poly(L-glutamic acid) dendron with pH sensitive hydrazine linkers to construct magnetic drug loaded nanocarriers.The structure of the dendron ligand was determined by 1H-NMR and ESI-TOF-MS.The poly(L-glutamic acid) dendron modified magnetic nanoparticles were characterized by TEM,SEAD,DLS and FTIR.The results showed that the crystalline structure of the magnetic cores were not varied after the ligand exchange,the modified magnetic nanoparticles exhibited excellent aqueous dispersity and stability.The DOX loading of modified magnetic nanoparticles with the average size of ca.63 nm was 52.4 mg·g-1.The release rate of DOX from the magnetic nanocarrier in the acid medium(pH=5.0) was dramatically higher than that in the physiological conditions(pH=7.4).The poly(L-glutamic acid) dendron modified magnetic nanoparticles showed excellent biocompatibility and low cytotoxicity in vitro,and the Fe3O4-G2(Glu)-DOX conjugate was efficient in inhibiting the proliferation of HeLa cells.Therefore,the pH sensitive peptide modified magnetic nanoparticle as a nanocarrier could be effectively utilized in drug delivery system.

Novel macrothiols for the synthesis of a structurally comprehensive dendritic library using thiol–ene click chemistry

In the last decades, the fabrication of ordered nano- and microporous structures has attracted increasing interest due to their specific properties and multiple possible applications in electronics, as templates or in the biological field. The development of such materials has been favored by the introduction of the simple breath-figure templating method in the 1990’s. In order to fully exploit the potential of these porous materials, the use of advanced functional molecules as precursors is essential. One suitable class of molecules is the well-defined linear-dendritic hybrids (LD hybrids) family. The structural variations, multiple end-groups and possible amphiphilicity of these molecules are significant advantages that could lead to highly sophisticated functional materials with potential usage in biology. Therefore, this project was directed towards the synthesis of advanced LD hybrids and the evaluation of their ability to form ordered functional porous films.A degradation and toxicity study was initially conducted on polyester-based 2,2-bis(methylol)propionic acid (bis-MPA) dendrimers under physiological conditions to support the potential usage of these molecules for biological purposes. The materials were found to undergo a relatively fast depolymerization process at pH 7.5. Moreover, the initial dendrimer and its decomposition products were proven to be non-toxic for immune competent cells, allowing for the utilization of these molecules for biological applications.A linear-dendritic-linear hybrid library was successfully synthesized from biocompatible poly(ethylene glycol) (PEG), poly(e-caprolactone) (PCL) and bis-MPA building blocks using a combination of ring-opening polymerization (ROP)and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The materials, consisting of one long PEG block connected to the focal point of the dendron and several PCL arms attached at its periphery, were used to construct ordered porous films using the breath figure method. The polymeric architecture strongly affected the ordering of the films with a more regular morphology obtained from a more flexible polymer. Changing the semi-crystalline PCL to amorphous polylactide (PLA) also permitted the formation of porous arrays. Interestingly, films obtained from inverted structures possessing one long PCL block and several short PEG chains, also presented a regular morphology. Moreover they could be activated to exhibit multiple surface hydroxyl groups.To increase the number of orthogonal synthetic methodologies available for the preparation of advanced macromolecules, high molecular weight dendritic macrothiols were synthesized. These molecules were efficiently coupled to a number of core molecules via thiol-ene coupling, generating a comprehensive library of dendritic materials. This approach represents an attractive alternative to the commonly used, but potentially toxic, CuAAC.Exploiting the obtained results, a final LD hybrid was synthesized from atom transfer radical polymerization (ATRP) of 2-hydroxyethyl methacrylate (HEMA) derivatives and thiol-ene coupling (TEC) with macrothiols. This macromolecule was successfully utilized to form functional ordered porous arrays and the availability of peripheral alkyne functional groups was demonstrated by efficient coupling with fluorescent Rhodamine-B. The HEMA-backbone allowed for the introduction of cross-linkable azide groups that were used to significantly improve the thermal stability of the films from 50 °C to 200 °C. These materials have the potential to be used in applications such as catalysis, in medicine and as sensors.

Preparation and Fluorescence Properties of Dendritic 8-Hydroxyquinoline and their Zinc Complexes

Two different dendritic 8-hydroxyquinoline ligands were synthesized through convergent approach, and the products were characterized by nuclear magnetic resonance (NMR) and infrared spectrometry (IR); the fluorescence properties of the dendritic 8-hydroxyquinoline ligands and the corresponding metallic complexes with Zn (II) were also studied by fluorescent spectrometry. The results show that the dendritic modifications of 8-hydroxyquinoline nucleus enhanced the intensity of luminescence, and the peripheral functional groups in the dendritic structure may affect the property of luminescence; the obvious red shift observed in the fluorescence profile of dendritic 8-hydroxyquinoline zinc provides it prospect of extensive application in the discipline of organic electroluminescent materials.

Direct Control of the Spatial Arrangement of Gold Nanoparticles in Organic–Inorganic Hybrid Superstructures

The directed assembly of gold nanoparticles is essential for their use in many kinds of applications, such as electronic devices, biological labels, and sensors. Herein an atomic alteration in the molecular structure of ligand-stabilized gold nanoparticles that can shift the interparticle distance up to 1 nm upon covalent coupling to organic-inorganic superstructures is presented. Gold nanoparticles are stabilized by two octadentate thioether ligands and have a mean diameter of 1.1 nm. The ligands contain a central rigid rod varying in length and terminally functionalized with a protected acetylene. The two peripheral functional groups on each particle enable the directed assembly of nanoparticles to dimers, trimers, and tetramers by oxidative acetylene coupling. This is a wet chemical protocol resulting in covalently bound nanoparticles. These organic-inorganic hybrid superstructures are analyzed by transmission electron microscopy, small angle X-ray scattering, and UV/vis spectroscopy. The focus of the comparison here is the subunit, which is anchoring the bridgehead, either a pyridine or benzene moiety. The pyridine-based ligands reflect the calculated length of the rigid-rod spacer in their interparticle distances in the obtained hybrid structures. This suggests a perpendicular arrangement that results from the coordination of the pyridine's lone pair to the gold surface. An atomic variation in the ligand's center leads to smaller interparticle distances in the case of hybrid structures obtained from benzene ligands. This large difference in the spatial arrangement suggests a tangential arrangement of the interparticle bridging structure in the latter case. Consequently a rather flat arrangement parallel to the particle surface must be assumed for the central benzene unit of the benzene-based ligand.

Modular peripheral functionalization of thiophene dendrons and dendrimers

A series of thiophene dendrons and dendrimers with peripheral functional groups were designed and synthesized. Two methodologies using thiophene dendrons and dendrons as synthetic building blocks, namely, (1) periphery functionalization; (2) a combination of focal and periphery functionalization have been demonstrated.

Synthesis of Shape‐Persistent Macrocycles by a One‐Pot Suzuki–Miyaura Cross‐Coupling Reaction

Shape-persistent macrocycles have attracted considerable interest as molecular components in the fields of supramolecular chemistry and materials science due to their unique molecular structures and properties. These rigid molecular rings with a nanoscale sized hole in the center may be tailored with specific chemical constitutions, geometrical shapes, peripheral functional groups, and so on. Recent advances in the preparation, supramolecular self-assembling, and practical applications of shape-persistent macrocycles have verified this class of molecules as promising building blocks for supramolecular chemistry and nanodevice fabrication. Intense efforts have been devoted to the synthesis of shape-persistent macrocycles, and they have been well summarized in several excellent reviews. The most successful methods used in the synthesis of shape-persistent macrocycles include the following approaches: 1) intramolecular ring closure of a,w-difunctionalized oligomer strategy and the one-pot intermolecular coupling and intramolecular cyclization method; 2) the template strategy; 3) thermodynamically controlled synthetic strategies. Based on these elegant synthetic strategies, a large number of shape-persistent macrocycles with well-defined shapes and sizes have been prepared and reported. Recently, Sherburn and Sinclair found that Suzuki– Miyaura coupling of diiodoaryls and arylboronic acid in a feed ratio of 10:1 afforded the product of double coupling in good yields. Hu and Dong demonstrated that the use of [Pd2ACHTUNGTRENNUNG(dba)3] and tBu3P as the catalyst precursor for Suzuki– Miyaura cross-coupling of dibromobenzenes with arylboronic acid (1 equiv) afforded exclusively diaryl-substituted benzenes. Scherf et al. reported the cross-coupling of 2,7-dibromofluorene with arylboronic acid (1 equiv) formed preferentially the diaryl-substituted fluorenes. Yokozawa et al. reported chain-growth Suzuki–Miyaura polymerization of an AB-type monomer, bromoarylboronic acid, using [PdBr{P ACHTUNGTRENNUNG(tBu)3}(Ph)] as an arylpalladium halide catalyst. Kiriy et al. have successfully grafted polyfluorene onto a functionalized surface by catalyst-transfer chain-growth Suzuki–Miyaura polycondensation of 7-bromo-9,9-bis(2ethyl-hexyl)-9H-fluoren-2-ylboric using [Pd ACHTUNGTRENNUNG(tBu3P)2] as the catalyst precursor. Very recently, Yokozawa et al. have demonstrated that catalyst-transfer Suzuki–Miyaura polycondensation can be used to prepare even diblock conjugated polymers with a narrow molecular weight distribution. We have recently demonstrated that the catalyst-transfer Suzuki–Miyaura cross-coupling (CTSMCC) reaction can be used to prepare hyperbranched polymers with a branching degree of 100%. We think the unique catalyst-transfer behavior can be used to prepare shape-persistent macrocycles. Herein, we report the application of the CTSMCC reaction in the preparation of shape-persistent macrocycles. To the best of our knowledge, this is the first example of the synthesis of macrocycles by the CTSMCC reaction. Four macrocycles were selected as targeted macrocycles to verify our idea. Due to the competition of linear polymerization, a onepot reaction usually affords macrocycles in very low yield. Therefore, the synthesis of shape-persistent macrocycles normally requires pseudo high dilution. The reactants are usually added to the reaction vessel by a syringe pump over [a] W. Huang, M. Wang, C. Du, Dr. Y. Chen, L. Su, C. Zhang, Prof. Dr. Z. Bo Institute of Chemistry CAS Beijing 100190 (P.R. China) Fax: (+86)10-82618587 E-mail : zsbo@iccas.ac.cn [b] Dr. R. Qin, Prof. Dr. Z. Liu, C. Li, Prof. Dr. Z. Bo Institute of Polymer Chemistry and Physics College of Chemistry, Beijing Normal University Beijing 100875 (P.R. China) Fax: (+86)10-62206891 E-mail : zsbo@bnu.edu.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201002574.

Synthesis of carbosilane dendrons and dendrimers derived from 1,3,5-trihydroxybenzene

Several carbosilane wedges of generations 1–3 have been synthesized, following the divergent method, containing at the focal point a C–Br bond and as peripheral functional groups SiMeCl 2, SiMe(C 3H 5) 2, SiMe 2Cl, SiMe 2H, and ester units SiMe 2{(C 3H 6)N(C 2H 4CO 2Me) 2}. The dendrons functionalized with SiMe(C 3H 5) 2 and SiMe 2{(C 3H 6)N(C 2H 4CO 2Me) 2} groups were used to synthesize spherical dendrimers derived from 1,3,5-(HO) 3C 6H 3, leaving the outer groups unchanged. The allyl dendrimers thus obtained were used as precursors to prepare new dendrimers functionalized with SiMeCl 2, SiMe 2Cl, SiMe 2H, amine units SiMe 2{(C 3H 6)NH 2} and also ester units SiMe 2{(C 3H 6)N(C 2H 4CO 2Me) 2}.

A double heteroatom Mitsunobu coupling with amino hydroxybenzoic acids on solid phase: a novel application of the Mitsunobu reaction to form dendron building blocks

A new highly efficient double heteroatom Mitsunobu coupling with amino hydroxybenzoic acids on solid phase is described. The synthetic routes reported in this work are general and applicable for the preparation of diverse building blocks, controlling protection, arm length, chirality, and peripheral functional groups. These novel units can form unusual dendritic architectures, which could be incorporated into specific complex structures, expanding the scope of dendrimer science.

Steric effects on [4+4]-photocycloaddition reactions between complementary anthracene derivatives

The steric effect of peripheral functional groups on the [4+4]-photocycloaddition between substituted anthracene derivatives was examined. The reactivity of 2,3,6,7-tetraphenylanthracene ( TPA) with 2-phenylanthracene ( PA), 2,9,10-trimethylanthracene ( TMA) and 9,10-dimethyl-2,3-diphenylanthracene ( DMDPA) was investigated. In all cases, the photodimers were formed in high yield despite the steric bulk of the peripheral substituents. It was further shown that although PA is capable of forming its homodimer, it selectively reacts with TPA when the latter is excited at 301 nm.