Polymorphism-driven Distinct Nanomechanical, Optical, Photophysical, and Conducting Properties in a Benzothiophene-quinoline.

Polymorphic forms of organic conjugated small molecules, with their unique molecular shapes, packing arrangements, and interaction patterns, provide an excellent opportunity to uncover how their microstructures influence their observable properties. Ethyl-2-(1-benzothiophene-2-yl)quinoline-4-carboxylate (BZQ) exists as dimorphs with distinct crystal habits - blocks (BZB) and needles (BZN). The crystal forms differ in their molecular arrangements - BZB has a slip-stacked column-like structure in contrast to a zig-zag crystal packing with limited π-overlap in BZN. The BZB crystals characterized by extended π-stacking along [100] demonstrated semiconductor behavior, whereas the BZN, with its zig-zag crystal packing and limited stacking characteristics, was reckoned as an insulator. Monotropically related crystal forms also differ in their nanomechanical properties, with BZB crystals being considerably softer than BZN crystals. This discrepancy in mechanical behavior can be attributed to the distinct molecular arrangements adopted by each crystal form, resulting in unique mechanisms to relieve the strain generated during nanoindentation experiments. Waveguiding experiments on the acicular crystals of BZN revealed the passive waveguiding properties. Excitation of these crystals using a 532 nm laser confirmed the propagation of elastically scattered photons (green) and the subsequent generation of inelastically scattered (orange) photons by the crystals. Further, the dimorphs display dissimilar photoluminescence properties; they are both blue-emissive, but BZN displays twice the quantum yield of BZB. The study underscores the integral role of polymorphism in modulating the mechanical, photophysical, and conducting properties of functional molecular materials. Importantly, our findings reveal the existence of light-emitting crystal polymorphs with varying electric conductivity, a relatively scarce phenomenon in the literature.

Discovery of Oxygen Induced Chemoselectivity in Pd-Catalyzed C-H Functionalization: Cross-Dehydrogenative Coupling vs C-H Amination.

We have come across a substrate namely, 5-benzoyl-pyrrolo[2,1-a]isoquinoline in which three different functionalizable C-H bonds were identified that could be judiciously transformed site selectively for the generation of complex polyring fused N-heterocycles. A Pd-catalyzed cross-dehydrogenative coupling of 5-benzoyl-pyrrolo[2,1-a]isoquinoline afforded 8H-indeno-pyrrolo[2,1-a]isoquinolinone and an oxygen induced palladium catalyzed selective C-H amination in the same substrate provided a pentacene viz., 9H-indolo-pyrrolo[2,1-a]isoquinoline. We also observed the formation of a multiring fused benzazepine scaffold by the site selective C-H amination in 5-(4-nitro benzoyl)-pyrrolo[2,1-a]isoquinoline.

Copper-Catalyzed Annulation of Electrophilic Benzannulated Heterocycles with 2-Aminopyridine and 2-Aminoquinoline: Direct Access toward Polyring-Fused Imidazo[1,2-a]pyridines.

We have developed a direct method for the synthesis of polyring-fused imidazo[1,2-a]pyridines via a copper-catalyzed annulation of electrophilic benzannulated heterocycles with 2-aminopyridine and 2-aminoquinoline. From 3-nitroindoles and 2-aminopyridine, we could synthesize tetracenes, viz., indole-fused imidazo[1,2-a]pyridines, and by starting from 2-aminoquinoline, we could generate pentacenes, viz., indolo-imidazo[1,2-a]quinolines. In addition, we could also extend the methodology toward the synthesis of benzothieno-imidazo[1,2-a]pyridines starting from 3-nitrobenzothiophene. Furthermore, the basic photophysical properties of these synthesized heteroacenes were evaluated.

Flexible organic crystals. Understanding the tractable co-existence of elastic and plastic bending.

As an emerging class of flexible materials, mechanically bendable molecular crystals are broadly classified as elastic or plastic. Nevertheless, flexible organic crystals with mutually exclusive elastic and plastic traits, with contrasting structural requirements, co-existing under different stress settings are exceptional; hence, it is imperative to establish the concurring factors that beget this rare occurrence. We report a series of halogen-substituted benzil crystals showing elastic bending (within ∼2.45% strain), followed by elastoplastic deformation under ambient conditions. Under higher stress settings, they display exceptional plastic flexibility that one could bend, twist, or even coil around a capillary tube. X-ray diffraction, microscopy, and computational data reveal the microscopic and macroscopic basis for the exciting co-existence of elastic, elastoplastic, and plastic properties in the crystals. The layered molecular arrangement and the weak dispersive interactions sustaining the interlayer region provide considerable tolerance towards breaking and making upon engaging or releasing the external stress; it enables restoring the original state within the elastic strain. Comparative studies with oxalate compounds, wherein the twisted diketo moiety in benzil was replaced with a rigid and coplanar central oxalate moiety, enabled us to understand the effect of the anisotropy factor on the crystal packing induced by the C[double bond, length as m-dash]O⋯C tetral interactions. The enhanced anisotropy depreciated the elastic domain, making the oxalate crystals more prone to plastic deformation. Three-point bending experiments and the determined Young's moduli further corroborate the co-existence of the elastic and plastic realm and highlight the critical role of the underlying structural elements that determine the elastic to plastic transformation. The work highlights the possible co-existence of orthogonal mechanical characteristics in molecular crystals and further construed the concurrent role of microscopic and macroscopic elements in attaining this exceptional mechanical trait.

Correction: I2/TBHP mediated diastereoselective synthesis of spiroaziridines.

Correction for 'I2/TBHP mediated diastereoselective synthesis of spiroaziridines' by Kizhakkan Thiruthi Ashitha et al., Org. Biomol. Chem., 2020, 18, 1588-1593, DOI: 10.1039/C9OB02711D.

Unprecedented access to functionalized pyrrolo[2,1-a]isoquinolines from the domino reaction of isoquinolinium ylides and electrophilic benzannulated heterocycles.

We have come across an unexpected reaction between electrophilic indoles and isoquinolinium methylides for accessing functionalized pyrrolo[2,1-a]isoquinolines. The reaction was found in general to yield the products in good yields. We also observed the formation of S-S-bridged bis-pyrrolo[2,1-a]isoquinolines from the reaction of 3-nitro benzothiophene and isoquinolinium methylides.

Advanced glycation end-products (AGE) trapping agents: Design and synthesis of nature inspired indeno[2,1-c]pyridinones.

Advanced glycation end products (AGEs) are implicated to be the key players in most of the diabetic complications. The AGE's interfere with the proteins heterogeneously, thereby rendering denaturation and the consequent loss of function and accumulation. Thus, a novel natural product inspired indeno[2,1-c]pyridinone (4a-4ad) molecular templates with AGE's trapping potential was designed through scaffold hopping approach and synthesized via facile two-step synthetic route. Amongst the tested indeno[2,1-c]pyridinone hybrids, 4i, 4x and 4aa exhibited excellent efficiency in trapping the AGE's. The percentage of antiglycation is measured by the analytical model system, i.e. via MG trapping capacity; here the compounds 4i, 4x and 4aa with 50.03%, 69.58%, and 93.37% respectively has displayed promising efficiency. In particular, 4aa demonstrated better activity than the positive control aminoguanidine (79.82%). The in-vitro toxicity of compounds was tested on L6 rat skeletal muscle cell lines revealed that none of the compounds showed any significant toxicity at concentrations up to 1000 µM.

Putative Biomimetic Route to 8-Oxabicyclo[3.2.1]octane Motif from a Humulene Sesquiterpenoid Zerumbone.

An approach to expand the diversity of terpenes to novel polycyclic skeletons with contiguous stereogenic centers is described. An unprecedented 8-oxabicyclo[3.2.1]octane motif was obtained in quantitative yield by photoirradiation of zerumbone in the presence of a catalytic amount of Lewis acid. The vital role of light in the isomerization of double bonds in zerumbone, which ensued cyclization via tertiary carbocation intermediate, emulates a biosynthetic route. Synthetic diversification of the phototransformed product afforded epoxy derivatives with up to seven contiguous stereogenic centers and eight-member ring fused tricyclic motifs. The present work sheds light on the possible role of UV irradiation in the biosynthesis of oxo-bridged tricyclic structures from polyene terpenes.

I2/TBHP mediated diastereoselective synthesis of spiroaziridines.

Eventhough spiroheterocycles are considered as emerging drug candidates, synthesis of spiroaziridines has not been well explored so far. Herein, we disclose an efficient I2/TBHP mediated diastereoselective synthesis of N-alkyl spiroaziridines from primary amines and easily accessible α,ß-unsaturated ketones. The reaction is also compatible for the synthesis of 2-aroylaziridines.

A new pentacyclic pyrylium fluorescent probe that responds to pH imbalance during apoptosis.

Efficient fluorophores with easy synthetic routes and fast responses are of great importance in clinical diagnostics. Herein, we report a new, rigid pentacyclic pyrylium fluorophore, PS-OMe, synthesised in a single step by a modified Vilsmeier-Haack reaction. Insights into the reaction mechanism facilitated a new reaction protocol for the efficient synthesis of PS-OMe which upon demethylation resulted in a "turn-on" pH sensor, PS-OH. This new fluorescent probe has been successfully used to monitor intracellular acidification at physiological pH. From the fluorescence image analysis, we were able to quantify the intracellular dynamic pH change during apoptosis. This new pH probe is a potential chemical tool for screening, drug discovery and dose determination in cancer therapy.

Phytochemical investigation on Myristica fragrans stem bark.

Myristica fragrans Houtt., the source of very important spice 'nutmeg' used world over is native to India, Indonesia, Sri Lanka, South Africa and Southeast Asia. Phytochemical investigation of M. fragrans stem bark led to the isolation of bis-aryl dimethyl tetrahydrofuran lignans, such as grandisin [(7S,8S,7'S,8'S)-3,3',4,4',5,5'-hexamethoxy-7,7',8,8'-lignan] and (7S,8S,7'R,8'R)-3,3',4,4',5,5'-hexamethoxy-7,7',8,8'-lignan along with important lignans and neolignans, licarinA, licarin B, odoratisol A, (2S, 3R)-7-methoxy-3-methyl-5-((E)-prop-1-enyl)-2-(5-methoxy,3,4-methylenedioxyphenyl)-2,3-dihydrobenzofuran, elemicin, fragransin B1, raphidecursinol B, erythro-(7S,8R)-Δ8'-4,7-dihydroxy-3,5,3'-trimethoxy-8-O-4'-neolignan, erythro-(7S,8R)-Δ8'-7-hydroxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan, surinamensin.and ß-sitosterol. Structures of the 12 compounds isolated were unambiguously identified by various spectroscopic methods. The former two compounds were isolated from M. fragrans for the first time. Furthermore, the X-ray crystal structure of odoratisol A is reported in this paper for the first time.

Molecular Basis for the Mechanical Response of Sulfa Drug Crystals.

Comprehension of the nanomechanical response of crystalline materials requires the understanding of the elastic and plastic deformation mechanisms in terms of the underlying crystal structures. Nanoindentation data were combined with structural and computational inputs to derive a molecular-level understanding of the nanomechanical response in eight prototypical sulfa drug molecular crystals. The magnitude of the modulus, E, was strongly connected to the non-covalent bond features, that is, the bond strength, the relative orientation with the measured crystal facet and their disposition in the crystal lattice. Additional features derived from the current study are the following. Firstly, robust synthons well isolated by weak and dispersive interactions reduce the material stiffness; in contrast, the interweaving of interactions with diverse energetics fortifies the crystal packing. Secondly, mere observation of layered structures with orthogonal distribution of strong and weak interactions is a prerequisite, but inadequate, to attain higher plasticity. Thirdly, interlocked molecular arrangements prevent long-range sliding of molecular planes and, hence, lead to enhanced E values. In a broader perspective, the observations are remarkable in deriving a molecular basis of the mechanical properties of crystalline solids, which can be exploited through crystal engineering for the purposeful design of materials with specific properties.

Synthesis of symmetrical and unsymmetrical triarylpyrylium ions via an inverse electron demand Diels-Alder reaction.

BF3·OEt2 mediated inverse electron demand Diels-Alder (IEDDA) reaction of chalcones with aryl acetylenes is reported for the synthesis of symmetrical and unsymmetrical 2,4,6-triarylpyrylium ions. The protocol provides an effective one-pot method for the utilization of readily available simple substrates under mild reaction conditions leading to a diverse array of pyrylium ions in moderately good yield.

Exploring nighttime road traffic noise: A comprehensive predictive surface for Toronto, Canada.

Road traffic noise can adversely impact the health of city residents, particularly when it occurs at night. The objective of this study was to evaluate nighttime traffic ambient noise in Toronto, Canada using measured and model-estimated noise levels. Road traffic noise was measured at 767 locations over 3 seasonal sampling campaigns between June 2012 and October 2013 to fully capture noise variability in Toronto. Temporal and campaign-specific spatial models, developed using the noise measurements, were used to build a final predictive surface. The surface was capable of estimating noise across the city over a 24-hr time frame. Measured and surface-estimated noise levels were compared with guidelines from the World Health Organization and the Province of Ontario to identify areas where noise may pose a health risk. Measured mean nighttime noise in Toronto exceeded World Health Organization (40 dBA) guidelines and mean daytime noise exceeded provincial (55 dBA) guidelines. The final predictive surface, incorporating spatial variables and daily cycles in noise levels, provides noise estimates geocoded for the entire study area. This tool could be used for epidemiological studies and to inform noise mitigation efforts. Based on surface-estimated noise levels during the quietest time of night (2 a.m.-2:30 a.m.), 100% of Toronto has nighttime noise exceeding 40 dBA (mean = 57 dBA, range = 49-110 dBA). A predictive surface was developed to estimate geocoded noise levels and facilitate further study of noise in Toronto. This tool can be used to assess road traffic noise, particularly at night, as an environmental health hazard.

Accessing highly functionalized cyclopentanoids via a cascade palladation approach: unprecedented benzylic C-H activation towards cyclopentenoindanes.

A Pd-catalyzed synthesis of 3,4,5-trisubstituted cyclopentenes from diazabicyclic olefins and o-iodobenzoates has been developed. The hitherto unknown cascade process involves three stages: carbopalladation, oxypalladation and a Tsuji-Trost reaction. We have also developed a facile route involving a novel benzylic C-H activation towards cyclopentenoindane moieties.

One-Pot MCR-Oxidation Approach toward Indole-Fused Heteroacenes.

A straightforward synthetic route toward indole-fused heteroacenes was developed. The strategy is composed of a one-pot process starting with a multicomponent reaction of cyclohexanone, primary amine and N-tosyl-3-nitroindole followed by an oxidation step. The one-pot approach was found to be general, affording both symmetric and nonsymmetric indolo[3,2-b]indoles in good yields. The strategy was also utilized for accessing 5-ring fused benzo[g]indolo[3,2-b]indole. We could extend the methodology for the synthesis of benzothieno[3,2-b]indoles starting from 3-nitrobenzothiophene. The importance of the developed method was exemplified by performing the reaction sequence on gram scale and also by the synthetic transformations of indolo[3,2-b]indoles. In addition, the change in photophysical properties with extension of conjugation of the synthesized heteroacenes was studied.

Metal-Free Multiple Carbon-Carbon and Carbon-Hydrogen Bond Activations via Charge-Switching Mechanism in Unstrained Diindolylmethanes.

A transformation of the unstrained phenol substituted 3,3'-diindolylmethanes (DIPMs) to 2,3'-diindolylketones (DIKs) by double C-C single bond cleavage with associated rearrangements, triggered by phenyliodine(III) diacetate (PIDA), is reported. Density functional theory studies reveal a mechanism involving multiple "charge-switching" steps by synergistic involvement of the two indole units with overall low activation energy. The indole 'charge-switching' mechanism in DIPMs was further extended toward synthesis of a natural product motif cyclohepta[b]indole from biaryl appended DIBM.

Antibacterial and antitubercular evaluation of dihydronaphthalenone-indole hybrid analogs.

A new series of indole appended dihydronaphthalenone hybrid analogs (5a-t) have been synthesized through the Lewis acid catalyzed Michael addition of indoles to the arylidene/hetero arylidene ketones. All the synthesized derivatives are well characterized through the 1 H-NMR, 13 C-NMR, HRMS spectroscopic techniques, compound 5r was further confirmed through single crystal X-ray analysis and screened for antibacterial and antitubercular activities. Among the synthesized compounds, the minimum inhibition concentration of 5l (against Escherichia coli) and 5o & 5p (against E. coli & Staphylococcus aureus) was found to be as low as 3.12 µg/ml as compared to the standard antibacterial drug ciprofloxacin 2.5 µg/ml. In antitubercular activity, compounds 5o and 5p with minimum inhibition concentration 6.25 µg/ml were found to be comparable with that of the drugs Pyrazinamide 5 µg/ml and Streptomycin 5 µg/ml. Compounds 5i, 5j, 5m, 5n, 5q, and 5r also showed promising activity against group of organisms tested.

NHC-Mediated Synthesis of Pyrrolo[2,1-a]isoquinolines and Their Photophysical Investigations.

An NHC-mediated synthesis of pyrrolo[2,1-a]isoquinoline and indolizine derivatives with potential biological activity is reported (NHC=N-heterocyclic carbene). The preliminary photophysical studies of such compounds reveal that they have potential application in the sensing of volatile organic compounds (VOCs).

Expedient Synthesis of Indolo[2,3-b]quinolines, Chromeno[2,3-b]indoles, and 3-Alkenyl-oxindoles from 3,3'-Diindolylmethanes and Evaluation of Their Antibiotic Activity against Methicillin-Resistant Staphylococcus aureus.

Easily accessible 3,3'-diindolylmethanes (DIMs) were utilized to generate a focused library of indolo[2,3-b]quinolines (2), chromeno[2,3-b]indoles (3), and 3-alkenyl-oxindoles (4) under 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-mediated oxidative conditions. DIMs with ortho-NHTosyl (NHTs) phenyl group afforded indolo[2,3-b]quinolines (2), whereas DIMs with ortho-hydroxy phenyl groups yielded chromeno[2,3-b]indoles (3) and 3-alkenyl-oxindoles (4). The mild conditions and excellent yields of the products make this method a good choice to access a diverse library of bioactive molecules from a common starting material. Two optimized compounds 2a and 2n displayed excellent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). Compound 2a showed the minimum inhibitory concentration values in the concentration between 1 and 4 µg/mL, whereas compound 2n revealed the values of 1-2 µg/mL. Furthermore, both the compounds were highly bactericidal and capable to kill the MRSA completely within 360 min. Collectively, the results suggested that both compounds 2a and 2n possess enormous potential to be developed as anti-MRSA agents.