Hexamethylene Spacer Research Articles

Synthesis of chlorophyll-BODIPY conjugates and their intramolecular excitation energy transfer

Zinc 3-hydroxymethyl-pyropheophorbides-[Formula: see text] covalently linked with an 8-aryl-1,3,5,7-tetramethyl-BODIPY moiety in the 17-substituent were synthesized by chemically modifying naturally occurring chlorophyll(Chl)-[Formula: see text]. The synthetic Chl–BODIPY conjugates in tetrahydrofuran exhibited sharp visible absorption and weak circular dichroism spectra, indicating that their molecules were fully dispersed in the solution. In their ground states, no intramolecular interaction between the Chl and BODIPY parts was observed. By contrast, singlet excitation energy was efficiently transferred from the photoexcited BODIPY moiety to zinc chlorin moiety within their molecules. The intramolecular energy transfer efficiencies exceeded 90% and were independent of the linkages including ester and amide bonds as well as methylene and hexamethylene spacers.

Effect of Flexible Spacer and Alkyl Tail Length on the Liquid Crystalline Phase Behavior of Fullerene Block Molecules.

Here the supramolecular liquid crystalline (LC) phase behavior of a series of fullerene block molecules was investigated regarding spacer length, alkyl tail length and temperature. These compounds exhibit several lamellar LC phases with different packings of self-organized fullerene two-dimensional (2D) crystals. With a short hexamethylene spacer, they form sandwich-like structures with triple or quadruple fullerene layers. By increasing the spacer length to 10 or 12 carbons, a composite layers-in-lamella superlattice structure with alternating soft hydrocarbon single layers and fullerene single or double layers was obtained. As the molecular configurational freedom between incompatible moieties was enhanced by the elongated spacer, the required cross-sectional fullerene-to-hydrocarbon ratio for the superlattice could be achieved despite of different volume fractions of the blocks. The superlattice phase range is efficiently widened by the design principle of constructing LC molecules with a long spacer, which also provides a facile way to tailor novel superstructures.

Melatonin-vorinostat hybrid ligands show higher histone deacetylase and cancer cell growth inhibition than vorinostat.

Anticancer drug conjugates are an emerging approach for future cancer treatment. Here, we report a series of hybrid ligands merging the neurohormone melatonin with the approved histone deacetylase (HDAC) inhibitor vorinostat, using melatonin's amide side chain (3a-e), its indolic nitrogen (5a-d), and its ether oxygen (7a-d) as attachment points. Several hybrid ligands showed higher potency thanvorinostat in both HDAC inhibition and cellular assays on different cultured cancer cell lines. In the most potent HDAC1 and HDAC6 inhibitors, 3e, 5c, and 7c, the hydroxamic acid moiety of vorinostat is linked to melatonin through a hexamethylene spacer. Hybrid ligands 5c and 7c were also found to be potent growth inhibitors of MCF-7, PC-3M-Luc, and HL-60 cancer cell lines. As these compounds showed only weak agonist activity at melatonin MT1 receptors, the findings indicate that their anticancer actions are driven by HDAC inhibition.

Flexible, Linear, and Systematically Expanded Tetraphosphonate Bolaamphiphiles and Their Inhibition Performance against Calcite and Barite Scale Formation

Oilfield scaling is one of the most prevalent water-based oilfield production problems. Chemical inhibitors are often used to combat and prevent scale deposition. The phosphonate functional group is commonly used in many scale inhibitors. A series of bolaamphiphilic alkyldiamine tetrakis(methylenephosphonic acid)s have been synthesized from 1,X-diamines, where X in the polymethylene spacer groups has an even number of 2–12 carbon atoms. These inhibitors were coined CX-T (X is the number of C atoms between the N atoms on the inhibitor backbone, and T stands for tetraphosphonates). All tetraphosphonates showed excellent compatibility with calcium ions at 100 ppm or less, i.e., normal scale inhibitor dosage levels. At higher dosages, the calcium concentration and length of the alkylene spacer chain between the nitrogen atoms also determine the compatibility. Crystal structures were determined for the calcium “complexes” with the tetraphosphonates C2-T, C4-T, C6-T, and C8-T. All tetraphosphonates were investigated for calcite and barite scale inhibition under dynamic conditions using oilfield produced waters based on the Heidrun field water composition, offshore Norway. For calcite scaling, tetraphosphonates with ethylene (2 carbons) and hexamethylene (6 carbons) spacer groups gave the best inhibition performance. For barite scaling, the best inhibition was observed for the tetraphosphonates with ethylene and tetramethylene spacer groups, which relates to the ability of both disphosphonate moieties to interact with a single barium ion.

Polyacrylate Backbone Promotes Photoinduced Reversible Solid-To-Liquid Transitions of Azobenzene-Containing Polymers

The development of polymers with efficient photoinduced reversible solid-to-liquid transitions is desirable for the design of healable materials, reconfigurable devices, and switchable adhesives. Herein, we demonstrate that an azobenzene-containing polyacrylate P-H exhibits more efficient photoinduced reversible solid-to-liquid transitions than its polymethacrylate analogue P-Me. The side chain of P-H or P-Me contains a hexamethylene spacer, a photoresponsive azobenzene group, and an n-decyl tail. Both P-H and P-Me show reversible cis–trans photoisomerization. Solid transP-H and P-Me change to liquid cis ones via UV-light-induced trans-to-cis isomerization; liquid cisP-H and P-Me revert to solid trans ones via visible-light-induced cis-to-trans back isomerization. Differential scanning calorimetry and rheology measurements revealed that photoinduced reversible solid-to-liquid transitions occur because P-H and P-Me have photoswitchable glass transition temperatures. Although P-Me exhibits a slightly faster rate for trans-to-cis photoisomerization than P-H due to fewer aggregates in solid state, cisP-H flows 20 times faster than cisP-Me because P-H has a more flexible polymer backbone. The low viscosity of cisP-H makes photoinduced solid-to-liquid transition efficient and enables the design of rapidly healable coatings. Our study shows that the design of a flexible backbone is a new strategy to develop rapidly healable polymers with more efficient photoinduced solid-to-liquid transitions.

Synthesis and In Vitro Neuroprotective Activity of Analogs with Various Spacer Lengths of a Dimeric Dipeptide Mimetic (GK-2) of Nerve Growth Factor

Dimeric dipeptide mimetic GK-2 or hexamethylenediamide bis-(N-monosuccinyl-L-glutamyl-L-lysine), which activated TrkA receptors and exhibited neuroprotective activity in vitro (10–5 – 10–9 M) and in vivo (0.05 – 5 mg/kg i.p.), was designed by us earlier based on the beta-turn of the nerve growth factor (NGF) fourth loop. The effect of dimerizing spacer length on the manifestation of neuroprotective activity was studied by synthesizing GK-2 (11 σ-bonds) analogs tetramethylenediamide bis-(N-monosuccinyl-L-glutamyl-Llysine) (GK-2c); pentamethylenediamide bis-(N-monosuccinyl-L-glutamyl-L-lysine) (GK-2b); and trimethylenediamide bis-(N-monosuccinyl-L-glutamyl-L-lysyl-6-aminohexanoic acid) (GK-2a) containing 9, 10, and 22 σ-bonds, respectively, between the lysine Cα-atoms of the dipeptide fragments. Neuroprotective activity was investigated in vitro using HT-22 mouse hippocampal neuronal cell culture under H2O2-induced oxidative stress and showed that the neuroprotective activity as measured by the minimum effective concentration was 104 times less if the distance between the dipeptide fragments increased from 11 to 22 σ-bonds. The neuroprotective activity decreased insignificantly if this distance was decreased from 11 to 10 σ bonds (GK-2b) and disappeared with 9 σ -bonds (GK-2c). Therefore, the hexamethylene spacer was optimal although the distance between the corresponding amino-acid moieties of natural NGF from an x-ray structure analysis was considerably greater at 33 σ-bonds. This contradiction could have arisen because two ionically bound mimetic molecules interacted with TrkA receptors. Another possible explanation was that TrkA molecules could approach closer in the presence of bis-dipeptide GK-2 than NGF.

Синтез и нейропротекторная активность <i>in vitro</i> аналогов димерного дипептидного миметика фактора роста нервов ГК-2 с разной длиной спейсера

Ранее нами на основе бета-изгиба 4-й петли фактора роста нервов получен димерный дипептидный миметик ГК-2, гексаметилендиамид бис-(N-моносукцинил-L-глутамил-L-лизина), который активировал TrkA-рецептор и проявлял нейропротекторную активность in vitro (10–5 – 10–9 М) и in vivo (0,05 – 5 мг/кг внутрибрюшинно). Для изучения влияния длины димеризующего спейсера на проявление нейропротекторной активности были синтезированы и исследованы аналоги ГК-2 (11 сигма-связей): тетраметилендиамид бис-(N-моносукцинил-L-глутамил-L-лизина) (ГК-2в); пентаметилендиамид бис-(N-моносукцинил-L-глутамил-L-лизина) (ГК-2б); триметилендиамид бис-(N-моносукцинил-L-глутамил-L-лизил-6-аминогексановой кислоты) (ГК-2а), содержащие соответственно 9, 10 и 22 сигма-связи между Ca-атомами лизина дипептидных фрагментов. Исследование нейропротекторной активности in vitro на нейрональной культуре HT-22 в условиях окислительного стресса, вызванного перекисью водорода, позволило установить, что при увеличении расстояния между дипептидными фрагментами от 11 до 22 сигма-связей происходит снижение нейропротекторного действия в 10000 раз по минимальной действующей концентрации. При уменьшении этого расстояния от 11 до 10 сигма-связей (ГК-2б) выраженность нейропротекторного действия незначительно снижается, а при 9 сигма связях (ГК-2г) активность исчезает. Таким образом, оптимальным является гексаметиленовый спейсер, несмотря на то, что расстояние по данным рентгеноструктурного анализа между соответствующими аминокислотными остатками в природном NGF существенно больше и соответствует 33 сигма-связям. Это противоречие может быть связано с тем, что во взаимодействии с TrkA-рецептором участвуют 2 молекулы миметика, связанные солеобразованием. Другое возможное объяснение состоит в том, что молекулы TrkA способны сближаться в присутствии бис-дипептида ГК-2 теснее, чем при участии NGF.

Аnticholinesterase and antioxidant activity of new binary conjugates of (с)-carbolines

This study presents the synthesis of binary tetrohydro-γ-carbolines with ditriazol spacers of varying length, which exhibit anticholinesterase and antioxidant activity, as compared to the original Dimebon prototype. Anticholinesterase activity suggests the potential ability of the new compounds to block β-amyloid aggregation induced by anticholinesterase, making them promising candidates for further research preparations for the treatment of Alzheimer's disease. Particular attention should be paid to the conjugate with an intertriazol hexamethylene spacer, which can be regarded as the leading compound in this series.

Synthesis and mesophase characterization of methacrylate based three phenyl ring core side chain liquid crystalline copolymers

A new series of side chain liquid crystalline copolymers consisting of a mesogenic monomer and a non-mesogenic n-butyl methacrylate are prepared by free radical solution polymerization. The mesogenic monomer is synthesized by a multistep route and is built with side arm core consisting of three phenyl rings linked by an ester and a terminal alkoxy chain at one end and hexamethylene spacer between methacyrlate unit and the phenyl ring core. The copolymers are synthesized with different feed ratios of liquid crystalline monomer and n-butyl methacrylate to realize composition dependent copolymers. The mesogenic monomers are characterized by FT-IR, 1H and 13C NMR while for a representative mesogen solution two-dimensional (2D) NMR experiments are also carried out. The hot-stage optical polarized microscopy, differential scanning calorimetry and variable temperature powder X-ray diffraction investigations revealed the existence of enantiotropic nematic (N) and smectic C (SC) mesophases for the copolymers. The weight average and number average molecular weight of the copolymers are found to be in the range 1.6×104 to 3.7×104g/mol from gel permeation chromatography. Thermal degradation profile of mesogenic copolymers investigated by thermogravimetric analysis revealed that the copolymers are stable till 335°C in nitrogen atmosphere. The copolymer compositions were determined using 1H NMR analysis.

Synthesis of pure silica MFI zeolites using imidazolium-based long dications. A comparative study of structure-directing effects derived from a further spacer length increase.

Length-dependent structure direction of linear methylimidazolium-based dications towards MFI zeolite, previously known only for the tetramethylene spacer, has also been found for octamethylene and decamethylene spacers. This works only under highly concentrated conditions, whereas dilution always tends to favor TON, a default structure that is the only zeolite obtained with the other reported dications (with tri-, penta-, and hexamethylene spacers). The locations and conformations of the dications have been studied by molecular mechanics simulations. As longer dications introduce lower density of positive charges in the zeolite, the density of connectivity defects also decreases. Finally, these long dications cannot easily place each charged imidazolium ring in the two possible orientations (either parallel or perpendicular to 4MR close to F- sites) found for the tetramethylene case. Hence, although the three MFI materials display two 19F NMR resonances at similar chemical shifts, their relative intensities strongly vary as a function of the spacer length.

Synthesis of fluorescent bisboronic acid sensors and their recognition of mono-/oligo-saccharides

Sensors capable of recognizing cell surface carbohydrates, such as sialyl Lewis X (sLex), are invaluable research tools and for the diagnosis and early detection of many forms of cancer. In this paper, we report the design and synthesis of a series of bisboronic acids 6(a–f) as fluorescent sensors towards mono-/oligosaccharides. Among them, compounds 6d and 6e showed strong binding affinities with glucose and fructose, while compound 6c, in which two anthracene-based boronic acid units were linked by a hexamethylene spacer, was able to recognize sLex selectivity and stained HEPG2 cells at 1μmol/L.

Thermal Amplification of Photoinduced Cooperative Reorientation of Liquid Crystalline Copolymer Films Comprised of N-Benzylideneaniline and Benzoic Acid Side Groups

This paper describes photoinduced cooperative molecular reorientation and its thermally stimulated amplification in liquid crystalline copolymethacrylates (LCPs) with hexamethylene spacer groups terminated with N-benzylideneaniline (NBA) and benzoic acid (BA) in the side chain. Influence of the copolymerization ratio and annealing temperature on the molecular reorientation behavior is investigated. Both NBA and BA side groups cooperatively reorient, but the orientation order depends on the copolymerization ratio. In contrast, sufficient thermal amplification of the photoinduced optical anisotropy is achieved for all LCPs, which is controlled by adjusting the annealing temperature.

Molecular and crystal structure of 2,11,14,17,20,23-hexaoxa-1,12(16,4α)-di-(19-nor-ent-beyerane)tetracosaphane-3,10,13,24-tetraone

The molecular and crystal structure of 2,11,14,17,20,23-hexaoxa-1,12(16,4α)-di-(19-nor-ent-beyerane)tetracosaphane-3,10,13,24-tetraone was determined by X-ray diffraction. This compound has a macrocyclic structure consisting of two molecules of the diterpenoid dihydroisosteviol (16-hydroxy-ent-beyeran-19-oic acid), which are linked by triethylene glycol and hexamethylene spacers. The compound crystallizes in the space group P21 with one independent molecule per asymmetric unit.

Preparation, characterisation and properties of sulphoxide modified polystyrene resins for solid-phase extraction of PtIV, RuIII and RuIV from hydrochloric acid

New sulphoxide modified resins were synthesized using poly(styrene-co-divinylbenzene) (PS-DVB) as matrix. Infrared spectroscopy and elemental analysis were used for characterisation. Solid-phase extraction of PtIV, RuIII and RuIV from acidic chloride solutions was performed via batch experiments. Influence of spacer length between sulphoxide and matrix (ethylene, hexamethylene), substitution of sulphoxide (R1: ethyl, hexyl, phenyl) and bead size of PS-DVB (spherical beads: d50<155μm, d50<80μm; powder: d50<30μm) on adsorption was investigated subjected to acidity. Experimental results showed that ethyl substituted sulphoxide immobilised onto ground PS-DVB and hexamethylene spacer exhibited best adsorption properties. Different kinetic models and isotherms were fitted to the experimental data to identify extraction mechanism. PtIV was quantitative sorbed at [HCl]⩽0.1mol/L whereas RuIII and RuIV sorption ranged between 90% and 95% at [HCl]⩾5mol/L. Desorption was reached using a solution of 0.5M thiourea (Tu) in 0.1M HCl at 90°C. Separation of PtIV and RuIII occurred at [HCl]⩽0.1mol/L whereas PtIV was extracted and RuIII remained in solution. A further separation was achieved by extracting PtIV and RuIV at 5M HCl followed by sequential elution of PtIV with concentrated HCl and RuIV with 0.5M Tu in 0.1M HCl at 90°C.

Synthesis and mesophase characterization of novel methacrylate based thermotropic liquid crystalline monomers and their polymers

A new series of side chain methacrylate monomers with a three phenyl ring core connected by an ester with a terminal alkoxy chain and hexamethylene spacer are synthesized by a multistep synthetic route. The corresponding polymers are realized by free radical solution polymerization. Two structurally similar mesogens are also synthesized for use as models to study the influence of the methacrylic unit on the mesophase characteristics. The molecular structure of the intermediates, monomers as well as the polymers is unambiguously confirmed by Fourier-transform infrared (FT-IR), solution 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and by elemental analysis. The mesophase characteristics of all of the monomers and polymers are determined by hot-stage optical polarized microscopy (HOPM) and differential scanning calorimetry (DSC). These investigations revealed the existence of enantiotropic nematic (N), smectic A (SA) and smectic C (SC) mesophases. Furthermore, for a representative monomer and polymer, the presence of the smectic phase is confirmed by variable temperature X-ray diffraction (XRD) where a characteristic layer ordering is noticed. The molecular weight of the polymers is determined by gel permeation chromatography (GPC) and the values are found to be typically in the range of 2.0 × 103 to 3.7 × 103. The mesogenic polymers are also found to be stable up to 320 °C by thermogravimetric analysis (TGA).

On-off switching properties of one-dimensional photonic crystals consisting of azo-functionalized polymer liquid crystals having different methylene spacers and polyvinyl alcohol

In this paper, photoresponsive behavior of multi-bilayered films having precisely controlled layer thickness prepared by stacking an azo-functionalized polymer liquid crystal, PMAzXAc, and polyvinyl alcohol alternatively, PVA, is described. The multi-bilayered films were found to reflect a light of specific wavelength depending on the layer thickness and refractive index, and showed the reversible change in the reflection intensity by irradiation with visible and UV lights. The change in the reflection intensity was brought about by change in the molecular orientation of PMAzXAc between an out-of-plane orientation and a photo-induced isotropic state, and was strongly dependent on the number of methylene spacer of PMAzXAc linking the azobenzene side group with the acrylate polymer main chain. PMAz6Ac with hexa-methylene spacer showed the largest change in the reflection intensity, while smaller change in the reflection intensity was observed for PMAzXAc having shorter or longer methylene spacer than 6. The effect of the methylene spacers on the photochemical change in the molecular orientation of azobenzene chromophores in the multi-bilayered films will be discussed.

Structure and catalytic activity of α-chymotrypsin in solutions of gemini surfactants

The regulatory effect of gemini alkylammonium surfactants (GSurf) with the hexamethylene spacer varying in the length of alkyl radicals on the structure and catalytic activity of a-chymotrypsin was studied. A correlation between the activity of a-chymotrypsin and the length of the alkyl radical of GSurf was found. Gemini surfactants enhance the enzyme activity below the critical micelle concentration (CMC) and inhibit that above the CMC. The results of IR spectroscopy and the data on tryptophan fluorescence show that the interaction of GSurf with a-chymotrypsin induces changes in the protein structure differed in intensity. The most probable enzyme complexes with GSurf were characterized by the molecular docking method.

Reorientation of photoreactive liquid crystalline polymer pattern fabricated by hybrid nanoimprinting

The molecular orientation of photoreactive liquid crystalline polymers can be controlled by linearly polarized ultraviolet (LPUV) irradiation and thermal treatment. Polymethacrylate with a hexamethylene spacer group terminated with 4-oxycinnamic acid on its side chain (P6CAM) is a photoreactive liquid crystalline polymer, and is reoriented parallel to the imprinted line upon thermal nanoimprinting. Thus, the molecular orientation of P6CAM could be controlled by LPUV irradiation or thermal nanoimprinting. Three dimensional molecular orientation may be induced in the P6CAM pattern by combining LPUV irradiation and thermal nanoimprinting (denoted hybrid nanoimprinting). Hybrid nanoimprinting of the photoreactive liquid crystalline polymer was carried out.

Three armed star mesogens based on 1,3,5-benzenetricarboxylic acid: Synthesis and mesophase characterization

A series of star mesogens based on 1,3,5-benzenetricarboxylic acid central core, side arms containing two phenyl rings, linked through azomethine groups and hexamethylene spacers, which connect the central core and side arms were synthesised via divergent approach. The mesogens synthesised and their intermediates were structurally well characterized, using FT-IR, 1H NMR, 13C NMR spectroscopy and elemental analysis techniques. The mesophase characterization was carried out using a hot stage-polarizing optical microscopy (POM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) techniques. Enantiotropic mesophases were observed for all the mesogens synthesised. An increase in the terminal chain length stabilized the smectic phase. Nematic phase was observed for the mesogens with short terminal chain length, whereas smectic polymorphism was observed on increasing the terminal chain length. XRD results suggested a tripod-like assembly of molecules in the mesophase.

Synthesis and Photoinduced Reorientation of Liquid Crystalline Polymers with Phenyl Thiobenzoate Side Groups

Liquid crystalline poly(meth)acrylates (LCPs) with 4-methoxyphenyl thiobenzoate side groups were synthesized to attain a photoinduced molecularly oriented structure, which is transparent in the visible region. The axis-selective photoreaction and photoinduced reorientation behaviors of the thin films were investigated using linearly polarized (LP) 313 nm light. The axis-selective photoreaction of the side groups generated an optical anisotropy in all the LCP films, but the amplitude depended on the alkylene spacer length and the type of the polymer main chain. The photoirradiated films were transparent in the visible region because the photoreacted products expressed less color. The axis-selective photoreaction of films followed by the thermally generated self-organization processes effectively induced an in-plane molecular reorientation perpendicularly to light polarization with an in-plane order parameter (S) of 0.62 and birefringence (Δn) ∼ 0.17, when the mesogenic groups were connected to the polymer main chain via hexamethylene spacers. In contrast, the out-of-plane reorientation dominated when the LCPs contained long alkylene spacers.