Gelation Kinetics-Structure Analysis of pH-triggered Low Molecular Weight Hydrogelators

Properties such as shear modulus, gelation time, structure of supramolecular hydrogels are strongly dependent on self-assembly, gelation triggering mechanism and processes used to form the gel. In our work we extend reported rheology analysis methodologies to pH-triggered supramolecular gels to understand structural insight using a model system based on N−N’ Dibenzoyl-L-Cystine pH-triggered hydrogelator and Glucono-δ-Lactone as the trigger. We observed that Avrami growth model when applied to time-sweep rheological data of gels formed at lower trigger concentrations provide estimates of fractal dimension which agree well compared with visualization of the microstructure as seen via Confocal Laser Scanning Microscopy, for a range of gelator concentrations.     

Copolymeric nano/microgels of N-isopropylacrylamide and carboxyalkyl methacrylamides: Effect of methylene chains and the ionization state of the weak acids on size and sensitivity to pH and temperature

ABSTRACT

We prepared nano/microgels by precipitation copolymerization of N-isopropylacrylamide (NIPAAm), and one of three different carboxyalkyl methacrylamides [methacryloylamido hexanoic acid (M₅), 8-methacryloylamido octanoic acid (M₇), and 11-methacryloylamido undecanoic acid (M₁₀)], either in the acid forms or as carboxylates (potassium salts). The hydrodynamic diameter (Dh) of the nano/microgels prepared with the carboxylates was smaller (≈100 nm for M₁₀ copolymers), compared to the size of homopolymeric NIPAAm microgels prepared by dispersion polymerization (around 600 nm), indicating that the carboxylates act as surfactants reducing the size of the seeds during the polymerization process. These materials presented a swollen-shrunken transition temperature (T _tr) similar to the T _tr of the homopolymeric NIPAAm microgels, without pH sensitivity. On the other hand, the copolymeric microgels prepared from the acid form of the comonomers have a similar or bigger size than NIPAAm microgels. For these copolymers, the T _tr can be tuned by the type and proportion of acid comonomer used and present pH sensitivity. This is important for biomedical applications such as positive temperature control release. Polyelectrolyte titration demonstrates that the nano/microgels prepared with the carboxylates behave as hard spheres, while the microgels prepared with the weak acid behave as porous materials.     

A Multi-Objective Approach for Drug Repurposing in Preeclampsia

Preeclampsia is a hypertensive disorder that occurs during pregnancy. It is a complex disease with unknown pathogenesis and the leading cause of fetal and maternal mortality during pregnancy. Using all drugs currently under clinical trial for preeclampsia, we extracted all their possible targets from the DrugBank and ChEMBL databases and labeled them as “targets”. The proteins labeled as “off-targets” were extracted in the same way but while taking all antihypertensive drugs which are inhibitors of ACE and/or angiotensin receptor antagonist as query molecules. Classification models were obtained for each of the 55 total proteins (45 targets and 10 off-targets) using the TPOT pipeline optimization tool. The average accuracy of the models in predicting the external dataset for targets and off-targets was 0.830 and 0.850, respectively. The combinations of models maximizing their virtual screening performance were explored by combining the desirability function and genetic algorithms. The virtual screening performance metrics for the best model were: the Boltzmann-Enhanced Discrimination of ROC (BEDROC)_α=160.9 = 0.258, the Enrichment Factor (EF)_1% = 31.55 and the Area Under the Accumulation Curve (AUAC) = 0.831. The most relevant targets for preeclampsia were: AR, VDR, SLC6A2, NOS3 and CHRM4, while ABCG2, ERBB2, CES1 and REN led to the most relevant off-targets. A virtual screening of the DrugBank database identified estradiol, estriol, vitamins E and D, lynestrenol, mifrepristone, simvastatin, ambroxol, and some antibiotics and antiparasitics as drugs with potential application in the treatment of preeclampsia.     

Limited path percolation in complex networks

We study the stability of network communication after removal of a fraction q=1-p of links under the assumption that communication is effective only if the shortest path between nodes i and j after removal is shorter than al(ij)(a> or =1) where l(ij) is the shortest path before removal. For a large class of networks, we find analytically and numerically a new percolation transition at p(c)=(kappa(0)-1)((1-a)/a), where kappa(0) [triple bond] / and k is the node degree. Above p(c), order N nodes can communicate within the limited path length al(ij), while below p(c), N(delta) (delta<1) nodes can communicate. We expect our results to influence network design, routing algorithms, and immunization strategies, where short paths are most relevant.     

Effect of mating delay on the ovary of Melipona quadrifasciata anthidioides (Hymenoptera: Apidae) queens

The effect of mating delay on the ovary structure of virgin queens of Melipona quadrifasciata anthidioides (Hymenoptera: Apidae) was investigated. Virgin queens 15, 20, 25 and 30 days old were dissected to analyze their degree of ovary degeneration. To verify whether the degeneration would cause permanent sterility, virgin queens of the same ages (15, 20, 25 and 30 days) were mated and accompanied for at least 14 days to verify whether there was physogastry and then dissected. The ovaries were analyzed by histology, histochemical tests and TUNEL to verify programmed cell death. The results showed that mating delay interrupted oogenesis preventing vitellogenesis. Mating delay results in ovary degeneration which increased with queen age. However, even when there was ovariole degeneration, 25-day-old virgin queens after mating presented normal ovariole activation.     

Shape-Adaptability and Redox-Switching Properties of a Di-Gold Metallotweezer

The use of a carbazolyl-connected di-gold(I) metallotweezer for the encapsulation of several electron-poor organic substrates, and a planar Au(III) complex containing a CNC pincer ligand, is described. The binding affinity of the receptor depends on the electron-deficient character of the planar guest, with larger association constants found for the more electron-poor guests. The X-ray diffraction molecular structures of two host:guest adducts show that the host approaches its arms in order to facilitate the optimum interaction with the surface of the planar guests, in a clear example of an guest-induced fit conformational arrangement. The electrochemical studies of the encapsulation of N,N’-dimethyl-naphthalenetetracarboxy diimide (NTCDI) show that the redox active guest is released from the receptor upon one electron reduction, thus constituting an example of redox-switchable binding.     

Solubility enhancement of ibuprofen using tri-ureasil-PPO hybrid: structural,cytotoxic, and drug release investigation

Herein, we used tri-ureasil organic–inorganic hybrid material (tU5000) in order to enhance the solubility of nonsteroidal anti-inflammatory drugs and fine tuning the drug delivery profile. For the first time, we used tU5000 as a film-forming agent in order to provide an alternative vehicle for transdermal drug delivery systems which the cell viability of practically 100 % for the highest and the lowest tested concentrations of pure tU5000 indicated that the material was not cytotoxic. The physicochemical properties of the tU5000 drug carrier and drug-loaded hybrids were systematically studied using powder X-ray diffraction, differential scanning calorimetry, small-angle X-ray scattering, and Fourier-transform infrared spectroscopy. The structural changes of tU5000 as well as the relationships between the drug content and in vitro drug release behaviors were investigated. The results showed that the ibu molecules were homogeneously distributed in the tU5000 xerogels contributing to fine-tuning the drug delivery profile. Considering the ability to incorporated high drug content, simple and mild preparation procedure by one-pot sol–gel route, high stability of the materials, sustained-release property, this class of hybrid based on polymers and inorganic compounds may have potential applications in the design of pharmaceutical formulation as ophthalmic (contact lenses), transdermal (patches) and implantable (soft tissue) drug delivery systems.     

Mono‐ and Bis(pyrrolo)tetrathiafulvalene Derivatives Tethered to C60: Synthesis,Photophysical Studies,and Self‐Assembled Monolayers

A series of mono‐ (MPTTF) and bis(pyrrolo)tetrathiafulvalene (BPTTF) derivatives tethered to one or two C₆₀ moieties was synthesized and characterized. The synthetic strategy for these dumbbell‐shaped compounds was based on a 1,3‐dipolar cycloaddition reaction between aldehyde‐functionalized MPTTF/BPTTF derivatives, two different tailor‐made amino acids, and C₆₀. Electronic communication between the MPTTF/BPTTF units and the C₆₀ moieties was studied by a variety of techniques including cyclic voltammetry and absorption spectroscopy. These solution‐based studies indicated no observable electronic communication between the MPTTF/BPTTF units and the C₆₀ moieties. In addition, femtosecond and nanosecond transient absorption spectroscopy revealed, rather surprisingly, that no charge transfer from the MPTTF/BPTTF units to the C₆₀ moieties takes place on excitation of the fullerene moiety. Finally, it was shown that the MPTTF–C₆₀ and C₆₀–BPTTF‐C₆₀ dyad and triad molecules formed self‐assembled monolayers on a Au(111) surface by anchoring to C₆₀.     

Physico-chemical and anatomical characterization of residual lignocellulosic fibers

Anatomical and physico-chemical properties of residual natural fibers (sugarcane bagasse, coconut fibers and peanut hulls) were characterized in order to evaluate their potential for use in the production of particleboard. The bulk density was determined by helium pycnometer and the chemical characteristics by using an electronic pH meter (for pH determination) on fibers dissolved in acidic and neutral detergents (to determine the levels of cellulose, hemicellulose and lignin). The anatomical characteristics were established using scanning electron microscopy coupled with an X-ray detector system, as well as energy dispersive X-ray spectroscopy. Results indicated similarities and differences between physico-chemical and anatomical characteristics of the residual lignocellulosic fibers when compared with the Pinus sp. wood commercially employed in particleboard production. Bulk density and pH for residual lignocellulosic fibers and Pinus sp. wood presented analogous values. Similar amounts of cellulose and lignin were identified between waste fibers and Pinus sp. wood. The presence of silica was identified in coconut fiber, peanut hull and sugarcane bagasse waste fibers, and may affect the mechanical characteristics of panels. Coconut and sugarcane bagasse fibers show surface pores with diameters ranging from 1.2 to 2.1 μm, below the 5 μm identified for Pinus sp. wood. Both fibers present pores distributed over their entire surface, whereas peanut hull fibers have no pores on their surface. This characteristic contributes to resin dispersion among particles, reflecting positively on the physical–mechanical properties of the panels. Particleboards produced with residual lignocellulosic fibers present similar physical–mechanical properties to those of Pinus sp. wood panels.     

Carbon Dioxide as a Protecting Group: Highly Efficient and Selective Catalytic Access to Cyclic cis‐Diol Scaffolds

The efficient and highly selective formation of a wide range of (hetero)cyclic cis‐diol scaffolds using aminotriphenolate‐based metal catalysts is reported. The key intermediates are cyclic carbonates, which are obtained in high yield and with high levels of diastereo‐ and chemoselectivity from the parent oxirane precursors and carbon dioxide. Deprotection of the carbonate structures affords synthetically useful cis‐diol scaffolds with different ring sizes that incorporate various functional groups. This atom‐efficient method allows the simple construction of diol synthons using inexpensive and accessible precursors and green metal catalysts and showcases the use of CO₂ as a temporary protecting group.