Sarveiskalvon permeabiliteetin ennustaminen QSPR-mallin avulla

QSPR-malli kuvaa kvantitatiivista riippuvuutta muuttujien ja biologisen ominaisuuden välillä. Näin ollen QSPR mallit ovat käyttökelpoisia lääkekehityksen apuvälineitä. Kirjallisessa osassa kerrotaan sarveiskalvon, suoliston ja veriaivoesteen permeabiliteetin malleista. Useimmin käytettyjä muuttujia ovat yhdisteen rasvaliukoisuus, polaarinen pinta-ala, vetysidosten muodostuminen ja varaus. Myös yhdisteen koko vaikuttaa läpäisevyyteen, vaikka tutkimuksissa onkin erilaista tietoa tämän merkittävyydestä. Malliin vaikuttaa myös muiden kuin mallissa mukana olevien muuttujien suuruusluokka esimerkkinä Lipinskin ‖rule of 5‖ luokittelu. Tässä luokittelussa yhdisteen ominaisuus ei saa ylittää tiettyjä raja-arvoja. Muussa tapauksessa sen imeytyminen suun kautta otettuna todennäköisesti vaarantuu. Lisäksi kirjallisessa osassa tutustuttiin kuljetinproteiineihin ja niiden toimintaan silmän sarveiskalvossa, suolistossa ja veriaivoesteessä. Nykyisin on kehitetty erilaisia QSAR-malleja kuljetinproteiineille ennustamaan mahdollisten substraatittien tai inhibiittorien vuorovaikutuksia kuljetinproteiinin kanssa. Kokeellisen osan tarkoitus oli rakentaa in silico -malli sarveiskalvon passiiviselle permeabiliteetille. Työssä tehtiin QSPR-malli 54 yhdisteen ACDLabs-ohjelmalla laskettujen muuttujien arvojen avulla. Permeabiliteettikertoimien arvot saatiin kirjallisuudesta kanin sarveiskalvon läpäisevyystutkimuksista. Lopullisen mallin muuttujina käytettiin oktanoli-vesijakaantumiskerrointa (logD) pH:ssa 7,4 ja vetysidosatomien kokonaismäärää. Yhtälö oli muotoa log10(permeabiliteettikerroin) = -3,96791 - 0,177842Htotal + 0,311963logD(pH7,4). R2-korrelaatiokerroin oli 0,77 ja Q2-korrelaatiokerroin oli 0,75. Lopullisen mallin hyvyyttä arvioitiin 15 yhdisteen ulkoisella testijoukolla, jolloin ennustettua permeabiliteettia verrattiin kokeelliseen permeabiliteettiin. QSPR-malli arvioitiin myös farmakokineettisen simulaation avulla. Simulaatiossa laskettiin seitsemän yhdisteen kammionestepitoisuudet in vivo vakaassa tilassa käyttäen simulaatioissa QSPR mallilla ennustettuja permeabiliteettikertoimia. Lisäksi laskettiin sarveiskalvon imeytymisen nopeusvakio (Kc) 13 yhdisteelle farmakokineettisen simulaation avulla ja verrattiin tätä lopullisella mallilla ennustettuun permeabiliteettiin. Tulosten perusteella saatiin tilastollisesti hyvä QSPR-malli kuvaamaan sarveiskalvon passiivista permeabiliteettia, jolloin tätä mallia voidaan käyttää lääkekehityksen alkuvaiheessa. QSPR-malli ennusti permeabiliteettikertoimet hyvin, mikä nähtiin vertaamalla mallilla ennustettuja arvoja kokeellisiin tuloksiin. Lisäksi yhdisteiden kammionestepitoisuudet voitiin simuloida käyttäen apuna QSPR-mallilla ennustettuja permeabiliteettikertoimien arvoja.

Chiral gels derived from secondary ammonium salts of (1R, 3S)-(+)-camphoric acid

In order to have access to chiral gels, a series of salts derived from (1R, 3S)-(+)-camphoric acid and various secondary amines were prepared based on supramolecular synthon rationale. Out of seven salts prepared, two showed moderate gelation abilities. The gels were characterized by differential scanning calorimetry, table top rheology, scanning electron microscopy, single crystal and powder X-ray diffraction. Structure property correlation based on X-ray diffraction techniques remain inconclusive indicating that some of the integrated part associated with the gelation phenomena requires a better understanding.

NO Reduction Over Noble Metal Ionic Catalysts

In last 40 years, catalysis for NO (x) removal from exhaust gas has received much attention to achieve pollution free environment. CeO(2) has been found to play a major role in the area of exhaust catalysis due to its unique redox properties. In last several years, we have been exploring an entirely new approach of dispersing noble metal ions in CeO(2) and TiO(2) for redox catalysis. We have extensively studied Ce(1-x) M (x) O(2-delta) (M = Pd, Pt, Rh), Ce(1-x-y) A (x) M (y) O(2-delta) (A = Ti, Zr, Sn, Fe; M = Pd, Pt) and Ti(1-x) M (x) O(2-delta) (M = Pd, Pt, Rh, Ru) catalysts for exhaust catalysis especially NO reduction and CO oxidation, structure-property relation and mechanism of catalytic reactions. In these catalysts, lower valent noble metal ion substitution in CeO(2) and TiO(2) creates noble metal ionic sites and oxide ion vacancy. NO gets molecularly adsorbed on noble metal ion site and dissociatively adsorbed on oxide ion vacancy site. Dissociative chemisorption of NO on oxide ion vacancy leads to preferential conversion of NO to N(2) instead of N(2)O over these catalysts. It has been demonstrated that these new generation noble metal ionic catalysts (NMIC) are much more catalytically active than conventional nano crystalline noble metal catalysts especially for NO reduction.

Crystal Engineering in the Desiraju Research Group in Bangalore

Over the years, crystal engineering has transformed into a mature and multidisciplinary subject. New understanding, challenges, and opportunities have emerged in the design of complex structures and structure-property evaluation. Revolutionary pathways adopted by many leaders have shaped and directed this subject. In this short essay to celebrate the 60th birthday of Prof. Gautam R. Desiraju, we, his current research group members, contemplate the development of some of the topics explored by our group in the context of the overall subject. These topics, though not entirely new, are of significant interest to the crystal engineering community.

Biomechanics of Substrate Boring by Fig Wasps: Role of Zinc in Insect Cuticle

There are many biomechanical challenges that a female insect must meet to successfully oviposit and ensure her evolutionary success. These begin with selection of a suitable substrate through which the ovipositor must penetrate without itself buckling or fracturing. The second phase corresponds to steering and manipulating the ovipositor to deliver eggs at desired locations. Finally, the insect must retract her ovipositor fast to avoid possible predation and repeat this process multiple times during her lifetime. From a materials perspective, insect oviposition is a fascinating problem and poses many questions. Specifically, are there diverse mechanisms that insects use to drill through hard substrates without itself buckling or fracturing? What are the structure-property relationships in the ovipositor material? These are some of the questions we address with a model system consisting of a parasitoid fig wasp - fig substrate system. To characterize the structure of ovipositors, we use scanning electron microscopy with a detector to quantify the presence of transition elements. Our results show that parasitoid ovipositors have teeth like structures on their tips and contain high amounts of zinc as compared to remote regions. Sensillae are present along the ovipositor to aid detection of chemical species and mechanical deformations. To quantify the material properties of parasitoid ovipositors, we use an atomic force microscope and show that tip regions have higher modulus as compared to remote regions. Finally, we use videography to show that ovipositors buckle during oviposition and estimate the forces needed to cause substrate boring based on Euler buckling analysis. Such methods may be useful for the design of functionally graded surgical tools.

Lead-free piezoelectric system (Na0.5Bi0.5)TiO3-BaTiO3: Equilibrium structures and irreversible structural transformations driven by electric field and mechanical impact

The structure-property correlation in the lead-free piezoelectric (1 - x)(Na0.5Bi0.5)TiO3-(x)BaTiO3 has been systematically investigated in detail as a function of composition (0 < x <= 0.11), temperature, electric field, and mechanical impact by Raman scattering, ferroelectric, piezoelectric measurement, x-ray, and neutron powder diffraction methods. Although x-ray diffraction study revealed three distinct composition ranges characterizing different structural features in the equilibrium state at room temperature: (i) monoclinic (Cc) + rhombohedral (R3c) for the precritical compositions, 0 <= x <= 0.05, (ii) cubiclike for 0.06 <= x <= 0.0675, and (iii) morphotropic phase boundary (MPB) like for 0.07 <= x < 0.10, Raman and neutron powder diffraction studies revealed identical symmetry for the cubiclike and the MPB compositions. The cubiclike structure undergoes irreversible phase separation by electric poling as well as by pure mechanical impact. This cubiclike phase exhibits relaxor ferroelectricity in its equilibrium state. The short coherence length (similar to 50A degrees) of the out-of-phase octahedral tilts does not allow the normal ferroelectric state to develop below the dipolar freezing temperature, forcing the system to remain in a dipolar glass state at room temperature. Electric poling helps the dipolar glass state to transform to a normal ferroelectric state with a concomitant enhancement in the correlation length of the out-of-phase octahedral tilt.

New solid forms of the anti-HIV drug etravirine: salts, cocrystals, and solubility

Thirteen new solid forms of etravirine were realized in the process of polymorph and cocrystal/salt screening to improve the solubility of this anti-HIV drug. One anhydrous form, five salts (hydrochloride, mesylate, sulfate, besylate, and tosylate), two cocrystals (with adipic acid and 1,3,5-benzenetricarboxylic acid), and five solvates (formic acid, acetic acid, acetonitrile, and 2:1 and 1:1 methanolates) were obtained. The conformational flexibility of etravirine suggests that it can adopt four different conformations, and among these, two are sterically favorable. However, in all 13 solid forms, the active pharmaceutical ingredient (API) was found to adopt just one conformation. Due to the poor aqueous solubility of the API, the solubilities of the salts and cocrystals were measured in a 50% ethanol water mixture at neutral pH. Compared to the salts, the cocrystals were found to be stable and showed an improvement in solubility with time. All the salts were dissociated within an hour, except the tosylate, which showed 50% phase transformation after 1 h of the slurry experiment. A structure property relationship was examined to analyze the solubility behavior of the solid forms.

Functional Corannulene: Diverse Structures, Enhanced Charge Transport, and Tunable Optoelectronic Properties

Chemical functionalization of various hydrocarbons, such as coronene, corannulene, and so forth, shows good promise in electronics applications because of their tunable optoelectronic properties. By using quantum chemical calculations, we have investigated the changes in the corannulene buckybowl structure, which greatly affect its electronic and optical properties when functionalized with different electron-withdrawing imide groups. We find that the chemical nature and position of functional groups strongly regulate the stacking geometry, -stacking interactions, and electronic structure. Herein, a range of optoelectronic properties and structure-property relationships of various imide-functionalized corannulenes are explored and rationalized in detail. In terms of carrier mobility, we find that the functionalization strongly affects the reorganization energy of corannulene, while the enhanced stacking improves hopping integrals, favoring the carrier mobility of crystals of pentafluorophenylcorannulene-5-monoimide. The study shows a host of emerging optoelectronic properties and enhancements in the charge-transport characteristics of functionalized corannulene, which may find possible semiconductor and electronics applications.

Photophysical, electrochemical and solid state properties of diketopyrrolopyrrole based molecular materials: importance of the donor group

Diketopyrrolopyrrole (DPP) based molecular semiconductors have emerged as promising materials for high performance active layers in organic solar cells. It is imperative to comprehend the origin of such a property by investigating the fundamental structure property correlation. In this report we have investigated the role of the donor group in DPP based donor-acceptor- donor (D-A-D) structure to govern the solid state, photophysical and electrochemical properties. We have prepared three derivatives of DPP with varying strengths of the donor groups, such as phenyl (PDPP-Hex), thiophene (TDPP-Hex) and selenophene (SeDPP-Hex). The influence of the donor units on the solid state packing was studied by single crystal X-ray diffraction. The photophysical, electrochemical and density functional theory ( DFT) results were combined to elucidate the structural and electronic properties of three DPP derivatives. We found that these DPP derivatives crystallized in the monoclinic space group P21/c and show herringbone packing in the crystal lattice. The derivatives exhibit weak p-p stacking interactions as two neighboring molecules slip away from each other with varied torsional angles at the donor units. The high torsional angle of 32 degrees ( PDPP-Hex) between the phenyl and lactam ring results in weak intramolecular interactions between the donor and acceptor, while TDPP-Hex and SeDPP-Hex show lower torsional angles of 9 degrees and 12 degrees with a strong overlap between the donor and acceptor units. The photophysical properties reveal that PDPP-Hex exhibits a high Stokes shift of 0.32 eV and SeDPP- Hex shows a high molar absorption co-efficient of 33 600 L mol -1 1 cm -1 1 with a low band gap of similar to 2.2 eV. The electrochemical studies of SeDPP- Hex indicate the pronounced effect of selenium in stabilizing the LUMO energy levels and this further emphasizes the importance of chalcogens in developing new n-type organic semiconductors for optoelectronic devices.

Design Aspects of Luminescent Organic Crystals

With the progress of modern material science and successful commercialisations of organic-electronics, the field of organic luminescent materials has gained much attention in recent years. For a long time, the concepts and knowledge of photoluminescence (i.e. fluorescence and phosphorescence) were restricted to the solution phase as the exceptions of fluorescence quenching in condensed state were yet to be discovered. However, in the last few decades, researchers around the globe have come up with a number of promising strategies and concepts to systematically design solid-state emissive organic materials. In particular, the manipulations of ordered solid state structures and intermolecular strong and weak interactions provide a basis for understanding structure-property relationship and serve as an important tool for the design of newer, better and more efficient luminescent materials. In this short review, recent developments in this field will be presented.

Shear induced crystallization in different polymorphic forms of PVDF induced by surface functionalized MWNTs in PVDF/PMMA blends

Shear induced crystallization in PVDF/PMMA blends, especially at higher fractions of PMMA, can be quite interesting in understanding the structure-property correlation and processing of these blends. In a recent submission (Phys. Chem. Chem. Phys., 2014, 16, 2693-2704), we clearly demonstrated, using dielectric spectroscopy, that the origin of segmental relaxations concerning the crystalline segments of PVDF in PVDF/PMMA blends in the presence of MWNTs (multiwalled nanotubes) was strongly contingent on the size of the crystallite. We now understand that the fraction of PMMA in the blends governs the origin of polymorphism in PVDF. This motivated us to systematically study the effect of shear on the crystallization behavior of PVDF especially in blends with different polymorphic forms of PVDF. Two model blends were selected; one with a mixture of alpha and beta crystals and the other predominantly rich in alpha crystals. Initially, physical ageing, at different oscillation frequencies (1 rad s(-1) and 0.1 rad s(-1)), was monitored by melt rheology and subsequently, the effect of steady shear was probed in situ without changing the history of the samples. Intriguingly, the rate of crystallization was observed to be significantly higher for higher oscillation frequencies, which essentially suggest that shear has induced crystallization in the blends. More interestingly, the effect of steady shear was more pronounced in the blends rich in alpha crystals (bigger crystallites as observed from SAXS) and at lower oscillation frequencies.

Fine-tuning solid-state luminescence in NPIs (1,8-naphthalimides): impact of the molecular environment and cumulative interactions

An investigation of a series of seven angular ``V'' shaped NPIs (1-7) is presented. The effect of substitution of these structurally similar NPIs on their photophysical properties in the solution-state and the solid-state is presented and discussed in light of experimental and computational findings. Compounds 1-7 show negligible to intensely strong emission yields in their solid-state depending on the nature of substituents appended to the oxoaryl moiety. The solution and solid-state properties of the compounds can be directly correlated with their structural rigidity, nature of substituents and intermolecular interactions. The versatile solid-state structures of the NPI siblings are deeply affected by the pendant substituents. All of the NPIs (1-7) show antiparallel dimeric pi-pi stacking interactions in their solid-state which can further extend in a parallel, alternate, orthogonal or lateral fashion depending on the steric and electronic nature of the C-4' substituents. Structural investigations including Hirshfeld surface analysis methods reveal that where strongly interacting systems show weak to moderate emission in their condensed states, weakly interacting systems show strong emission yields under the same conditions. The nature of packing and extended structures also affects the emission colors of the NPIs in their solid-states. Furthermore, DFT computational studies were utilized to understand the molecular and cumulative electronic behaviors of the NPIs. The comprehensive studies provide insight into the condensed-state luminescence of aggregationprone small molecules like NPIs and help to correlate the structure-property relationships.

Using heat treatment effects and EBSD analysis to tailor microstructure of hybrid Mg nanocomposite for enhanced overall mechanical response

In this study, a detailed investigation on the effect of heat treatment on the microstructural characteristics, texture evolution and mechanical properties of Mg-(5.6Ti+2.5B(4)C)(BM) hybrid nanocomposite is presented. Optimised heat treatment parameters, namely, heat treatment temperature and heat treatment time, were first identified through grain size and microhardness measurements. Initially, heat treatment of composites was conducted at temperature range between 100 and 300 degrees C for 1 h. Based on optical microscopic analysis and microhardness measurements, it was evident that significant grain growth and reduction in microhardness occurred for temperatures > 200 degrees C. The cutoff temperature that caused significant grain growth/matrix softening was thus identified. Second, at constant temperature (200 degrees C), the effect of variation of heat treatment time was carried out (ranging between 1 and 5 h) so as to identify the range wherein increase in average grain size and reduction in microhardness occurred. Furthering the study, the effect of optimised heat treatment parameters (200 degrees C, 5 h) on the microstructural texture evolution and hence, on the tensile and compressive properties of the Mg-(5.6Ti+2.5B(4)C)(BM) hybrid nanocomposite was carried out. From electron backscattered diffraction (EBSD) analysis, it was identified that the optimised heat treatment resulted in recrystallisation and residual stress relaxation, as evident from the presence of similar to 87% strain free grains, when compared to that observed in the non-heat treated/as extruded condition (i.e. 2.2 times greater than in the as extruded condition). For the heat treated composite, under both tensile and compressive loads, a significant improvement in fracture strain values (similar to 60% increase) was observed when compared to that of the non-heat treated counterpart, with similar to 20% reduction in yield strength. Based on structure-property correlation, the change in mechanical characteristics is identified to be due to: (1) the presence of less stressed matrix/reinforcement interface due to the relief of residual stresses and (2) texture weakening due to matrix recrystallisation effects, both arising due to heat treatment.

A bio-attuned ratiometric hydrogen sulfate ion selective receptor in aqueous solvent: structural proof of the H-bonded adduct

A new cell permeable quinazoline based receptor (1) selectively senses HSO4- ions of nanomolar region in 0.1 M HEPES buffer (ethanol-water: 1/5, v/v) at biological pH over other competitive ions through the proton transfer followed by hydrogen bond formation and subsequent anion coordination to yield the LHSO4]-LH+center dot 3H(2)O (2) ensemble, which has been crystallographically characterised to ensure the structure property relationship. This non-cytotoxic HSO4- ion selective biomarker has great potential to recognize the intercellular distribution of HSO4- ions in HeLa cells under fluorescence microscope.

Modulation of Electronic and Self-Assembly Properties of a Donor-Acceptor-Donor-Based Molecular Materials via Atomistic Approach

The performance of molecular materials in optoelectronic devices critically depends upon their electronic properties and solid-state structure. In this report, we have synthesized sulfur and selenium based (T4BT and T4BSe) donor-acceptor-donor (D-A-D) organic derivatives in order to understand the structure-property correlation in organic semiconductors by selectively tuning the chalcogen atom. The photophysical properties exhibit a significant alteration upon varying a single atom in the molecular structure. A joint theoretical and experimental investigation suggests that replacing sulfur with selenium significantly reduces the band gap and molar absorption coefficient because of lower electronegativity and ionization potential of selenium. Single-crystal X-ray diffraction analysis showed differences in their solid-state packing and intermolecular interactions. Subsequently, difference in the solid-state packing results variation in self-assembly. Micorstructural changes within these materials are correlated to their electrical resistance variation, investigated by conducting probe atomic force microscopy (CP-AFM) measurements. These results provide useful guidelines to understand the fundamental properties of D-A-D materials prepared by atomistic modulation.