Para Position Research Articles

Exploring Alternative Pathways to Target Bacterial Type II Topoisomerases Using NBTI Antibacterials: Beyond Halogen-Bonding Interactions.

Novel bacterial topoisomerase inhibitors (NBTIs) are a new class of antibacterial agents that target bacterial type II topoisomerases (DNA gyrase and topoisomerase IV). Our recently disclosed crystal structure of an NBTI ligand in complex with DNA gyrase and DNA revealed that the halogen atom in the para position of the phenyl right hand side (RHS) moiety is able to establish strong symmetrical bifurcated halogen bonds with the enzyme; these are responsible for the excellent enzyme inhibitory potency and antibacterial activity of these NBTIs. To further assess the possibility of any alternative interactions (e.g., hydrogen-bonding and/or hydrophobic interactions), we introduced various non-halogen groups at the p-position of the phenyl RHS moiety. Considering the hydrophobic nature of amino acid residues delineating the NBTI's binding pocket in bacterial topoisomerases, we demonstrated that designed NBTIs cannot establish any hydrogen-bonding interactions with the enzyme; hydrophobic interactions are feasible in all respects, while halogen-bonding interactions are apparently the most preferred.

Efficient removal of p-arsanilic acid and arsenite by Fe(II)/peracetic acid (Fe(II)/PAA) and PAA processes

The widespread occurrence of p-arsanilic acid (p-ASA) in natural environments poses big threats to the biosphere due to the generation of toxic inorganic arsenic (i.e., As(III) and As(V), especially As(III) with higher toxicity and mobility). Oxidation of p-ASA or As(III) to As(V) followed by precipitation of total arsenic using Fe-based advanced oxidation processes demonstrated to be a promising approach for the treatment of arsenic contamination. This study for the first time investigated the efficiency and inherent mechanism of p-ASA and As(III) oxidation by Fe(II)/peracetic acid (Fe(II)/PAA) and PAA processes. p-ASA was rapidly degraded by the Fe(II)/PAA process within 20 s at neutral to acidic pHs under different conditions, while it was insignificantly degraded by PAA oxidation alone. Lines of evidence suggested that hydroxyl radicals and organic radicals generated from the homolytic OO bond cleavage of PAA contributed to the degradation of p-ASA in the Fe(II)/PAA process. p-ASA was mainly oxidized to As (V), NH4+, and p-aminophenol by the Fe(II)/PAA process, wherein the aniline group and its para position were the most vulnerable sites. As(III) of concern was likely generated as an intermediate during p-ASA oxidation and it could be readily oxidized to As(V) by the Fe(II)/PAA process as well as PAA alone. The in-depth investigation demonstrated that PAA alone was effective in the oxidation of As(III) under varied conditions with a stoichiometric molar ratio of 1:1. Efficient removal (> 80%) of total arsenic during p-ASA oxidation by Fe(II)/PAA process or during As(III) oxidation by PAA process with additional Fe(III) in synthetic or real waters were observed, mainly due to the adsorptive interactions of amorphous ferric (oxy)hydroxide precipitates. This study systematically investigates the oxidation of p-ASA and As(III) by the Fe(II)/PAA and PAA processes, which is instructive for the future development of arsenic remediation technology.

A symmetrical carbazole/benzonitrile-based high triplet energy bipolar host designed by a para-linkage strategy for efficient blue and green phosphorescent organic light-emitting diodes

Based on a para-linkage concept, a symmetrical carbazole-benzonitrile derivative of 4-(9H-carbazol-9-yl)-3,5-diphenyl-2,6-difluoronitrile (CzPhFBN) was designed and prepared as a host for phosphorescent organic light-emitting diodes (PhOLEDs). In the CzPhFBN molecular, a cyano (CN) unit and a carbazole (Cz) unit were attached to the central phenyl ring at the para positions. Simultaneously, the Cz group was surrounded by two phenyl units to increase structure distortion for high triplet energy and CN unit was surrounded by two F units to improve electron transporting behavior. The photophysical properties and carrier transport behavior of CzPhFBN were investigated. The results demonstrated that CzPhFBN offered a high triplet energy of exceeding 3.0 eV and bipolar carrier transporting property. By incorporating CzPhFBN as the host, the blue FIrpic- and green Ir(ppy)3-based PhOLEDs with a common device configuration delivered the maximum efficiencies of 11.1%/19.7 cd A−1/12.1 lm W−1 and/13.1%/43.6 cd A−1/28.6 lm W−1, respectively. These results indicate that this study provides a potential design strategy of high triplet energy bipolar host materials with a simple and elegant structure.

Proton tautomerism in 5-dimethylaminomethylidene-4-(o-,m-,p-hydroxyphenyl)amino-1,3-thiazol-2(5H)-ones: synthesis, crystal structure and spectroscopic studies.

Three new 5-dimethylaminomethylidene-4-phenylamino-1,3-thiazol-2(5H)-ones with an hydroxyl group in the ortho-, meta- and para- positions on the phenyl ring were synthesized in order to deduce the structural changes occurring on prototropic tautomerism of the amidine system. The existence of all the title compounds solely in the amino tautomeric form has been established in the solid and liquid (dimethyl sulfoxide solution) phases. The title compounds are analyzed from the point of view of the electronic effects and conformational freedom of their molecules. The intermolecular interactions in the crystals and their supramolecular architecture are highlighted.

Leveraging a Structural Blueprint to Rationally Engineer the Rieske Oxygenase TsaM.

Rieske nonheme iron oxygenases use two metallocenters, a Rieske-type [2Fe-2S] cluster and a mononuclear iron center, to catalyze oxidation reactions on a broad range of substrates. These enzymes are widely used by microorganisms to degrade environmental pollutants and to build complexity in a myriad of biosynthetic pathways that are industrially interesting. However, despite the value of this chemistry, there is a dearth of understanding regarding the structure-function relationships in this enzyme class, which limits our ability to rationally redesign, optimize, and ultimately exploit the chemistry of these enzymes. Therefore, in this work, by leveraging a combination of available structural information and state-of-the-art protein modeling tools, we show that three "hotspot" regions can be targeted to alter the site selectivity, substrate preference, and substrate scope of the Rieske oxygenase p-toluenesulfonate methyl monooxygenase (TsaM). Through mutation of six to 10 residues distributed between three protein regions, TsaM was engineered to behave as either vanillate monooxygenase (VanA) or dicamba monooxygenase (DdmC). This engineering feat means that TsaM was rationally engineered to catalyze an oxidation reaction at the meta and ortho positions of an aromatic substrate, rather than its favored native para position, and that TsaM was redesigned to perform chemistry on dicamba, a substrate that is not natively accepted by the enzyme. This work thus contributes to unlocking our understanding of structure-function relationships in the Rieske oxygenase enzyme class and expands foundational principles for future engineering of these metalloenzymes.

Transdermal Delivery of α-Aminophosphonates as Semisolid Formulations-An In Vitro-Ex Vivo Study.

α-Aminophosphonates are organophosphorus compounds with an obvious similarity with α-amino acids. Owing to their biological and pharmacological characteristics, they have attracted the attention of many medicinal chemists. α-Aminophosphonates are known to exhibit antiviral, antitumor, antimicrobial, antioxidant and antibacterial activities, which can all be important in pathological dermatological conditions. However, their ADMET properties are not well studied. The aim of the current study was to provide preliminary information about the skin penetration of three preselected α-aminophosphonates when applying them as topical cream formulations in static and dynamic diffusion chambers. The results indicate that aminophosphonate 1a, without any substituent in the para position, shows the best release from the formulation and the highest absorption through the excised skin. However, based on our previous study, the in vitro pharmacological potency was higher in the case of para-substituted molecules 1b and 1c. The particle size and rheological studies revealed that the 2% cream of aminophosphonate 1a was the most homogenous formulation. In conclusion, the most promising molecule was 1a, but further experiments are proposed to uncover the possible transporter interactions in the skin, optimize the topical formulations and improve PK/PD profiles in case of transdermal delivery.

Structure-activity relationship of dihydropyridines for rhabdomyosarcoma

Childhood muscle-related cancer rhabdomyosarcoma is a rare disease with a 50-year unmet clinical need for the patients presented with advanced disease. The rarity of ∼350 cases per year in North America generally diminishes the viability of large-scale, pharmaceutical industry driven drug development efforts for rhabdomyosarcoma. In this study, we performed a large-scale screen of 640,000 compounds to identify the dihydropyridine (DHP) class of anti-hypertensives as a priority compound hit. A structure-activity relationship was uncovered with increasing cell growth inhibition as side chain length increases at the ortho and para positions of the parent DHP molecule. Growth inhibition was consistent across n = 21 rhabdomyosarcoma cell line models. Anti-tumor activity in vitro was paralleled by studies in vivo. The unexpected finding was that the action of DHPs appears to be other than on the DHP receptor (i.e., L-type voltage-gated calcium channel). These findings provide the basis of a medicinal chemistry program to develop dihydropyridine derivatives that retain anti-rhabdomyosarcoma activity without anti-hypertensive effects.

Effect of substitution on light-curable properties in diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide: DFT and TD-DFT calculations

Acylphosphine oxide-based photoinitiators have been used in digital light processing (DLP) 3D printing slurry to prepare ceramic materials. However, the limitation is how to improve the absorption efficiency of photoinitiator in UV–Vis light and its initiation efficiency. In this study, through the DMol3 module of Materials Studio, the hydrogen atom is substituted by different electron-donating substituents (-NH2, -OCH3, -OH), substitution positions (ortho, meta, para) and tri-substitutions positions (2,4,6 and 3,4,5) were systematically studied respectively, including the change from the ground state to the first excited state, energy gap, ultraviolet-visible spectrum, the excitation energy, absorption wavelength, and oscillator strength. These results show that the order of electron-donating ability of these four groups is as follows: -NH2 > -OCH3 > -OH> -H. When the initiation wavelength λ≤ 425 nm, enhancing the electron-donating ability of the substituent and substitute para-substitution position can improve the oscillator strength and cause a blue-shift of the absorption peak. 4-TPO-NH2 which has the strongest electron-donating ability group substituted in para position shows the highest oscillator strength (21.5%) and blue shift (22 nm) compared with unsubstituted TPO. When the initiation wavelength λ≥ 425 nm, enhancing the electron-donating ability of the substituent, substitute para-substitution or ortho-substitution position, and tri-substituents of 2,4,6 positions, is the most beneficial to improve the oscillator strength and the red-shift of the absorption peak. Compared to unsubstituted TPO, 2,4,6-TPO-NH2 has 9.00 times increase in oscillator strength with 122 nm red-shift, and 2-TPO-NH2 has 134 nm red-shift with 2.53 times increase in oscillator strength. Furthermore, these studies can improve the development of acylphosphine oxide-based photoinitiators, and will also help to expand the application of DLP 3D printing in ceramic fields.

Direct Arylation of C(sp2)–H Bonds in Anilines

AbstractAnilines selectively arylated at their ortho, meta or para positions are useful building blocks in synthesis and have found applications in many areas. The most straightforward method for their synthesis relies on the direct arylation of a C(sp2)–H bond of anilines, an attractive strategy avoiding the prefunctionalization of the starting anilines provided that such arylations proceed with high levels of regioselectivity. Such reactions are presented and discussed, in a comprehensive manner, in this review article, with an emphasis on the regioselectivity of the processes and factors governing both the reactivity and selectivity. 1 Introduction2 ortho-Arylation of Anilines2.1 Direct C(sp2)–H ortho-Arylation of Anilines2.2 Directed C(sp2)–H ortho-Arylation of Anilines3 meta-Arylation of Anilines4 para-Arylation of Anilines4.1 Direct C(sp2)–H para-Arylation of Anilines via Oxidative Radical Homodimerization4.2 Direct C(sp2)–H para-Arylation of Anilines via Transition-Metal Catalysis5 Conclusion and Outlook

Sulfide, Sulfoxide, and Sulfone Substitution: Electron Structure Modulation from Para‐D‐π‐B to Para‐A‐π‐B in Multiple‐Resonance Emitters with Narrowband Emission and High Color Purity

AbstractMulti‐resonance thermally activated delayed fluorescence (MR‐TADF) emitters have been studied to address the issue of the broadband emission in organic light‐emitting diodes (OLEDs). Herein, the authors have systematically investigated the effect of electron‐donating or ‐withdrawing units in the para position of B atom on the optoelectronic emission modulation BCz‐BN MR‐TADF emitters. Due to the enhanced spin‐orbit coupling (SOC) effect, BN(p)SCH3 with electron structure of para‐D‐π‐B is synthesized by introducing a heavy S atom into the para position of B atom of BCz‐BN. By oxidizing BN(p)SCH3, BN(p)SOCH3 and BN(p)SO2CH3 with electron structure of para‐A‐π‐B have been synthesized. The quantum simulations and photophysical studies have illustrated BN(p)SCH3 can exhibit large reverse intersystem crossing rate constant (kRISC) of 6.4 × 104 s−1 due to the large SOC constants and small singlet‐triplet energy splitting (ΔEST) of 0.12 eV. BN(p)SOCH3 and BN(p)SO2CH3 with electron structure of para‐A‐π‐B displayed red‐shift emissions with smaller full‐width at half‐maximum (FWHM) values of ≈21 nm and kRISC values owing to enhanced ΔEST and the low emission contribution of the triplet excitons in contrast to those of BN(p)SCH3 with electron structure of para‐D‐π‐B. Consequently, BN(p)SCH3‐based OLEDs show highly efficient blue emission with an external quantum efficiency (EQE) of 26.2% and excellent color purity.

Phenylazothiazoles as Visible-Light Photoswitches.

A novel class of photoswitches based on a phenylazothiazole scaffold that undergoes reversible isomerization under visible-light irradiation is reported. The photoswitch, which comprises a thiazole heteroaryl segment directly connected to a phenyl azo chromophore, has very different spectral characteristics, such as a redshifted absorption maximum wavelength and well-separated absorption bands of the trans and cis isomers, than conventional azobenzene and other heteroaryl azo compounds. Substituents at the ortho and para positions of the phenyl ring of the photoswitch resulted in a further shift to longer wavelengths up to 525 nm at the absorption maximum with a small thermal stability compensation. These photoswitches showed excellent photostationary distributions of the trans and cis isomers, thermal half-lives of up to 7.2 h, and excellent reductant stability. The X-ray crystal structure analysis revealed that the trans isomers exhibited a planar geometry and the cis isomers exhibited a T-shaped orthogonal geometry. Detailed ab initio calculations further demonstrated the plausible electronic transitions and isomerization energy barriers, which were consistent with the experimental observations. The fundamental design principles elucidated in this study will aid in the development of a wide variety of visible-light photoswitches for photopharmacological applications.

Effect of Substituents on the Intramolecular n→π* Interaction in 3-[2-(Dimethylamino) phenyl] propanal: A Computational Study

n→π* non-covalent interaction (NCI) and hydrogen bond have similarity in terms of delocalization of the electron density between the two orbitals involved in the interaction. Hydrogen bond (X-H···Y) involves delocalization of the lone pair electrons (n) on the Y atom into the σ* orbital of the X-H bond. In contrast, the n→π* interaction deals with delocalizing the lone pair electrons (n) on the N, O, or S atom into the π* orbital of a C═O group or aromatic ring. Herein, we have shown a resemblance of this weak n→π* interaction with the relatively stronger hydrogen bond in terms of folding the side chains in flexible molecules. This work reports the study of folding of the flexible side-chain in 3-[2-(dimethylamino) phenyl] propanal (DMAPhP) through a N···C═O n→π* interaction using various computational approaches such as NBO, QTAIM, and NCI analyses. The folding of the molecule by the n→π* interaction observed in this study is found to be similar to that present in the secondary structures of peptides or proteins through hydrogen bonding interactions. Interestingly, the stabilization of the global minimum conformer of DMAPhP by the n→π* interaction demonstrates the importance of this NCI in providing conformational preferences in molecular systems. Another important finding of this study is that the theoretical redshift obtained in the C═O stretching frequency of the most stable conformer of the DMAPhP is contributed mostly by the n→π* interaction as the C═O group is not involved in hyperconjugation with any neighboring heteroatom, which is a common phenomenon in any ester or amide. We have also demonstrated here that the strength of the intramolecular n→π* interaction can be modulated by varying the electronic substituents at the para position of the donor group involved in the interaction.

A refreshing perspective on electrochromic materials: Phenoxazine as an opportune moiety towards stable and efficient electrochromic polyimides

In our attempt to develop appealing EC materials, here we address the electrochromic materials field by employing the aryl-substituted phenoxazine (POZ) as a new member of triarylamine family with excellent potential for electrochromic applications. Thus, a simple synthetic strategy was followed to build a novel POZ-based diamine that was further used in polycondensation reaction with commercially available aromatic dianhydrides to develop three novel polyimides (PIs). Complementarily, POZ-based model compounds were synthesized to get insights into the electrochemical and electrochromic behavior of the synthesized PIs. With the support of the computational quantum mechanical modeling methods (Density-Functional Theory – DFT and Time-Dependent (TD)–DFT), the mechanism responsible for the absence of the dimerization process upon POZ oxidation was established. Without resorting to any structural modification to block the para position of POZ, the present PIs demonstrated exquisite electrochemical and electrochromic performance, including high redox stability during 100 repetitive cyclic voltammetry scans, unique deep-purple coloration during oxidation, high optical contrast, up to 62%, response time below 6.5 s for coloring and 5.1 s for bleaching, excellent electrochromic efficiency, up to 193 cm2/C and a maximum 21% decay of the electrochromic efficiency after 500 cycles. The most efficient EC polyimide was used as an active layer in electrochromic prototype devices to survey the full applicative potential of these PIs. The devices rendered an optical contrast of 51%, 7.9 s for coloring, and 7.2 s for bleaching, electrochromic efficiency of 178 cm2/C, and decay of the electrochromic efficiency of 6.1% after 100 cycles, placing for the first time the POZ-based PIs among the perspective electrochromic materials.

Tuning Photophysical Properties via Positional Isomerization of the Pyridine Ring in Donor–Acceptor-Structured Aggregation-Induced Emission Luminogens Based on Phenylmethylene Pyridineacetonitrile Derivatives

A series of aggregation-induced emission (AIE)-featured phenylmethylene pyridineacetonitrile derivatives named o-DBCNPy ((Z)-3-(4-(di-p-tolylamino)phenyl)-2-(pyridin-2-yl)acrylonitrile), m-DBCNPy ((Z)-3-(4-(di-p-tolylamino)phenyl)-2-(pyridin-3-yl)acrylonitrile), and p-DBCNPy ((Z)-3-(4-(di-p-tolylamino)phenyl)-2-(pyridin-4-yl)acrylonitrile) have been synthesized by tuning the substitution position of the pyridine ring. The linkage manner of the pyridine ring had influences on the molecular configuration and conjugation, thus leading to different photophysical properties. The absorption and fluorescence emission peak showed a bathochromic shift when the linking position of the pyridine ring changed from the meta to the ortho and para position. Meanwhile, o-DBCNPy exhibited the highest fluorescence quantum yield of 0.81 and the longest fluorescence lifetime of 7.96 ns as a neat film among all three isomers. Moreover, non-doped organic light-emitting diodes (OLEDs) were assembled in which the molecules acted as the light-emitting layer. Due to the relatively prominent emission properties, the electroluminescence (EL) performance of the o-DBCNPy-based OLED was superior to those of the devices based on the other two isomers with an external quantum efficiency (EQE) of 4.31%. The results indicate that delicate molecular modulation of AIE molecules could endow them with improved photophysical properties, making them potential candidates for organic photoelectronic devices.

Investigation of the influence of persulfurated benzene derivatives on optical and carrier mobility properties

In this research, two persulfurated benzene molecules consisting of amine and carboxylic acid derivatives were designed, synthesized and the effect of substitution in para position on absorption, fluorescence, and aggregation induced emission (AIE) were investigated. Moreover, taking into account the simpler method, the space charge limited current (SCLC) was considered and the temperature dependence on carrier mobility (μ) of the derivatives was investigated. The maximum value of hole mobility (μh) at 298 K was calculated to be 7.50 × 10-4cm2Vs at an electric field of 900 V0.5cm0.5. Since the crystallite size of the compound consisting of the NH2 group was higher (100.07 nm), the (μ) at 298 K and 77 K were also higher than the other counterpart. As a result, the NH2 substitution played a more effective role in increasing the (μ).

Precursors for the Development of π-Conjugated Low-Coordinate Phosphorus Compounds.

The synthesis of a novel monomeric precursor and its butadiyne-bridged dimeric form for the preparation of novel π-conjugated organophosphorus compounds is presented. The precursors are synthesized from commercially available starting materials, and based on a Dmp (2,6-dimesitylphenyl) group for kinetic stabilization of the P-functionality, a bromo substituent for the introduction of the phosphorus center, and an acetylene unit at the para position of the Dmp moiety. Such acetylenic units are synthetically versatile, and can be explored for the construction of larger phosphorus-containing π-conjugates. The precursors are utilized to prepare Dmp-stabilized C,C-dibromophosphaalkenes, and butadiyne-bridged dimeric species thereof. The effect of the low-coordinate phosphorus centers and the extent of π-conjugation on the spectroscopic and electronic properties is evaluated by NMR and UV/Vis spectroscopy, as well as cyclic voltammetry. In addition to the phosphaalkenes, the successful syntheses of two new diphosphenes are presented, indicating a broad applicability of the precursor.

Benzothiazole Clubbed Imidazolone Derivatives: Synthesis, Molecular Docking, DFT Studies, and Antimicrobial Studies.

This study aims to synthesize antimicrobial agents and their molecular docking, and DFT studies of benzothiazole-imidazolone scaffolds. Benzothiazole and imidazolone analogues are of interest due to their potential activity against microbial infections. In search of suitable antimicrobial compounds, we report here the synthesis, characterization, and biological activities of benzothiazole and imidazolone analogues (4a-l). The benzothiazole clubbed imidazolone motifs were synthesized, characterized, and screened for their antimicrobial activity. Molecular docking was carried out for the development of antimicrobial agents based on the results of biological activity obtained. We have synthesized a new series of benzothiazole-clubbed imidazolone hybrids by using multi-step reactions in the search for antimicrobial agents (4a-l). The structures were determined by 1H NMR, 13C NMR, IR, and mass spectroscopy techniques. Moreover, synthesized compounds were evaluated for their antimicrobial activity by using a Serial Broth Dilution method. In addition, molecular electrostatic potential, geometric optimization, and molecular reactivity analyses (HOMO-LUMO) of 4c, which is one of the compounds with the highest antibacterial activity, were performed. The in vitro antimicrobial activity was evaluated against pathogenic strains. Among them, compounds 4c showed the most potent biological activity against Gram-negative bacteria, E. coli with MIC values of 50 μg/mL, and compound 4c active against A. clavatus with MIC values of 100 μg/mL. Active compound 4c HUMO-LUMO energies, molecular electrostatic potential analysis, and geometric optimization parameters were calculated with a 6-31G ** base set using DFT/B3LYP theory, and the results were displayed. Molecular docking studies were performed on E. coli DNA Gyrase B to understand the binding interaction of compound 4c, and it was observed that compound 4c interacted with Arg76 amino acid of the active site through hydrophobic interaction. Benzothiazole-clubbed imidazolone hybrids (4a-l) indicated promising antimicrobial activity. Among them, compounds 4b (MIC=50 μg/mL C. albicans), 4c (MIC=50 μg/mL, E. coli), 4e (MIC= 100 μg/mL, A. niger), and 4g (MIC= 50 μg/mL, S. pyogenes) with electronwithdrawing bromo, chloro, and fluoro group at the para position of the phenyl ring on benzothiazole-imidazolone hybrids indicated remarkable potency compared to the standard drug. The geometric optimization, molecular reactivity, and MESP analyses of 4c were calculated with the B3LYP/6-31G ** base set and ΔE = ELUMO-EHOMO, which was found to be - 0.12096 eV. In addition, the binding affinity scores correlated well with the in vitro antimicrobial activity (4c), while their binding modes proposed the involvement of steric, electrostatic, and hydrogen- bonding interactions with the active site.

Synthesis, in silico Studies and Pharmacological Evaluation of a New Series of Indanone Derivatives as Anti-Parkinsonian and Anti-Alzheimer's Agents.

Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common forms of neurodegenerative disorders. The aim of the current work is to study the potential of some new indanone derivatives for the treatment of these neurological disorders. A new series of 4-(2-oxo-2-aminoethoxy)-2-benzylidene substituted indanone derivatives have been synthesized and studied for anti-Parkinsonian and anti-Alzheimer's effects. Substitution of different aminoalkyl functionalities at the para position of 2-benzylidene moiety of indanone ring resulted in the formation of potent anti-parkinsonian and anti-Alzheimer's agents (5-10). The neuroprotective effects of newly synthesized compounds were evaluated using perphenazine (PPZ)-induced catatonia in rats and LPS-induced cognitive deficits in mice models. Further, in silico molecular modelling studies of the new indanone derivatives were performed by docking against the 3D structures of various neuroinflammatory mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monoamine oxidase-B (MAO-B), to gain the mechanistic insights of their anti-Alzheimer's and antiparkinsonian effects. The newly synthesized indanone analogues 5-10 were found effective against PPZinduced motor dysfunction and LPS-induced memory impairment in animal models. Among all the synthesized analogues, morpholine-substituted indanone 9 displayed maximum anti-parkinsonian activity, even better than the standard drug L-DOPA, while pyrrolidine and piperidine substituted analogues 5 and 6 were found to be the most potent anti-Alzheimer's agents. The new 2-arylidene-1-indanone analogues show good potential as promising leads for designing compounds against Parkinson's and Alzheimer's diseases.

Design and synthesis of strong root gravitropism inhibitors with no concomitant growth inhibition

Herein, we describe a highly potent gravitropic bending inhibitor with no concomitant growth inhibition. Previously, we reported that (2Z,4E)-5-phenylpenta-2,4-dienoic acid (ku-76) selectively inhibits root gravitropic bending of lettuce radicles at 5 μM. Based on the structure–activity relationship study of ku-76 as a lead compound, we designed and synthesized various C4-substituted analogs of ku-76. Among the analogs, 4-phenylethynyl analog exhibited the highest potency for gravitropic bending inhibition, which was effective at only 0.01 μM. Remarkably, 4-phenylethynyl analog is much more potent than the known inhibitor, NPA. Substitution in the para position on the aromatic ring of 4-phenylethynyl group was tolerated without diminished activity. In addition, evaluation using Arabidopsis indicated that 4-phenylethynyl analog inhibits gravitropism by affecting auxin distribution in the root tips. Based on the effects on Arabidopsis phenotypes, 4-phenylethynyl analog may be a novel inhibitor that differs in action from the previously reported auxin transport inhibitors.

Electronic effect of substituents regulates the photocatalytic activity of PhC2Cu

To examine the electronic effect of substituents on the photocatalytic performance of PhC2Cu, two organometallic photocatalysts with either an F-atom (4F-P) or a CH3-group (4CH3-P) substituent at the phenyl ring para position were prepared by a facile one-step aqueous-phase method. Density functional theory calculations of the three organometallic photocatalysts (4F-P, P and 4CH3-P) revealed the substituent electronic effect on the frontier orbital energies and on the charge density at the Cu+ ion. This study indicates that the introduction of the strongly electron-withdrawing F atom facilitates the effective separation of the photo-generated charge carriers, while the introduction of the electron-donating CH3 group inhibits it. Consequently, the 4F-P photocatalyst exhibits greater photo-degradation activity compared to 4CH3-P and unsubstituted P. This investigation has shown that the introduction of a strongly electron-withdrawing substituent group is an effective strategy to improve the photocatalytic activity.