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We are reporting a palladium catalyzed microwave assisted halogenation of 3-phenyl-2H-benzo[b][1,4]oxazine-2-ones.

As of 2 September 2021, United States nursing homes have reported675,000 COVID-19 cases and134,000 deaths according to the Centers for MedicareMedicaid Services (CMS). More than 205,000,000 persons in the United States had received at least one dose of a COVID-19 vaccine (62% of total population) as of 2 September 2021. We investigate the role of vaccination in controlling future COVID-19 outbreaks. We developed a stochastic, compartmental model of SARS-CoV-2 transmission in a 100-bed nursing home with a staff of 99 healthcare personnel (HCP) in a community of 20,000 people. We parameterized admission and discharge of residents in the model with CMS data, for a within-facility basic reproduction number (R

An environment-friendly approach for regioselective acylation of 1-methyl-3-phenyl quinoxaline-2(1H)-ones was developed using water as a solvent. The protocol exhibits a wide substrate scope and employs commercially available, non-toxic acyl surrogates.

A sustainable and environment-friendly approach for the regioselective acylation of 1-methyl-3-phenyl quinoxaline-2(1

Synthesis of various symmetric and asymmetric 1,4-DHP linked 1,2,3-triazole derivatives from economical and readily available starting materials via a convenient methodology in a single-pot method ...

From the viewpoint of meeting the current green chemistry challenges in chemical synthesis, there is a need to disseminate how the cocktail of acylation and activation can play a pivotal role in affording bioactive acylated products comprising substituted ketone motifs in fewer reaction steps, with higher atom-economy and improved selectivity. In recent years, a significant number of articles employing the title compounds "aldehydes" as magnificent acylation surrogates which are less toxic and widely applicable have been published. This review sheds light on the compounds use for selective acylation of arene, heteroarene and alkyl (sp3, sp2 and sp) C-H bonds by proficient utilization of the C-H activation strategy. Critical insights into selective acylation of diverse moieties for the synthesis of bioactive compounds are presented in this review that will enable academic and industrial researchers to understand the mechanistic aspects involved and fruitfully employ these strategies in designing novel molecules. ispartof: ORGANIC & BIOMOLECULAR CHEMISTRY vol:18 issue:40 pages:7987-8033 ispartof: location:England status: published

Prediction of spatial heterogeneity in disease incidence based on measurable spatial factors is a major goal of spatial epidemiology. There are a number of applied goals of these predictions, including appropriately targeting resources for surveillance and intervention and accurately quantifying disease burden. Although spatial heterogeneity is evident in the epidemiology of many diseases, several aspects of the biology of vector-borne diseases amplify this form of heterogeneity. Here, we review several aspects of this biology, highlighting seven distinct ways in which the biology of vector-borne diseases impacts understanding spatial heterogeneity in disease incidence. Whereas traditional methods place emphasis on spatial regression and other forms of statistical analysis of empirical data, the goal here is to offer a perspective on potential pitfalls of analyses that take data at face value and do not acknowledge the complex, nonlinear, and dynamic relationships between spatial patterns of disease incidence and spatial heterogeneity in transmission.

In an effort to develop potent anti-inflammatory agents, a series of novel chroman derivatives including acyclic amidochromans, chromanyl esters and chromanyl acrylates have been designed, synthesized and fully characterized. These chroman analogues were screened for their anti-inflammatory activities through inhibition of the TNF-α-induced ICAM-1 expression on human endothelial cells. A structure-activity relationship was also established and it has been found that in the case of carboxy chromans and amidochromans, the chain length of the amide moiety, branching of the side chain and the presence of the substituents on the phenyl ring have significant effects on their inhibitory activities, while in chromanyl acrylates, the number of methoxy groups, their relative positions on the phenyl ring, and presence of functional groups in the α,β-unsaturated ester moiety played a critical role on their activities. Compound 14 (N-hexyl-7-hydroxy-2,2-dimethylchromane-6-carboxamide) was found to be the most potent compound in inhibiting the TNF-α-induced expression of ICAM-1 on endothelial cells. This journal is

Concern is emerging regarding the challenges posed by spatial complexity for modelling and managing the area-wide elimination of parasitic infections. While this has led to calls for applying heterogeneity-based approaches for addressing this complexity, questions related to spatial scale, the discovery of locally-relevant models, and its interaction with options for interrupting parasite transmission remain to be resolved. We used a data-driven modelling framework applied to infection data gathered from different monitoring sites to investigate these questions in the context of understanding the transmission dynamics and efforts to eliminate Simulium neavei- transmitted onchocerciasis, a macroparasitic disease that causes river blindness in Western Uganda and other regions of Africa. We demonstrate that our Bayesian-based data-model assimilation technique is able to discover onchocerciasis models that reflect local transmission conditions reliably. Key management variables such as infection breakpoints and required durations of drug interventions for achieving elimination varied spatially due to site-specific parameter constraining; however, this spatial effect was found to operate at the larger focus level, although intriguingly including vector control overcame this variability. These results show that data-driven modelling based on spatial datasets and model-data fusing methodologies will be critical to identifying both the scale-dependent models and heterogeneity-based options required for supporting the successful elimination of S. neavei-borne onchocerciasis.

The eradication of malaria remains challenging due to the complex life cycle of Plasmodium and the rapid emergence of drug-resistant forms of Plasmodium falciparum and Plasmodium vivax. New, effective, and inexpensive antimalarials against multiple life stages of the parasite are urgently needed to combat the spread of malaria. Here, we synthesized a set of novel hydroxyethylamines and investigated their activities in vitro and in vivo. All of the compounds tested had an inhibitory effect on the blood stage of P. falciparum at submicromolar concentrations, with the best showing 50% inhibitory concentrations (IC50) of around 500 nM against drug-resistant P. falciparum parasites. These compounds showed inhibitory actions against plasmepsins, a family of malarial aspartyl proteases, and exhibited a marked killing effect on blood stage Plasmodium. In chloroquine-resistant Plasmodium berghei and P. berghei ANKA infected mouse models, treating mice with both compounds led to a significant decrease in blood parasite load. Importantly, two of the compounds displayed an inhibitory effect on the gametocyte stages (III-V) of P. falciparum in culture and the liver-stage infection of P. berghei both in in vitro and in vivo. Altogether, our findings suggest that fast-acting hydroxyethylamine-phthalimide analogs targeting multiple life stages of the parasite could be a valuable chemical lead for the development of novel antimalarial drugs.

A one-pot, four-component methodology have been developed for the synthesis of coumarin-linked triazolyl-dihydropyrimidinones (DHPM). The Biginelli reaction was combined with the click reaction for the first time in a sequential multicomponent tandem reaction approach. A series of ten such compounds have been synthesised and examined for their fluorescent properties. These were found to emit violet-blue light in the visible region of the spectrum with very high Stoke's shift values. The compounds have demonstrated high quantum yields which makes them attractive targets for their utilization as new fluorescent probes. The electronic structure of these coumarin-based donor-pi-acceptor (D-pi-A)-type organic dyes have been studied by Density Functional Theory (DFT). Thermal analysis of few of the compounds show that they are stable up to temperature range of 0-290 degrees C. The synthesised compounds have been characterised by NMR and mass spectrometry.

An efficient palladium-catalysed C H functionalization sequence has been developed for the synthesis of 2-aminoimidazole alkaloids (Kealiinine C) and its analogues. This protocol proceeds via iodocyclisation of propargylguanidines followed by intramolecular Pd-catalysed cyclisation.

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim A microwave-assisted highly efficient intermolecular C−H functionalization sequence has been developed to access substituted isoquinolones using α-amino acid esters as a directing group. This methodology enables a wide range of N-benzoyl α-amino ester derivatives to react via a Ru-catalysed C−H bond activation sequence, to form isoquinolones with moderate to excellent yields. As an additional advantage, our strategy proved to be widely applicable and also enabled the reaction of alkenes to provide access to alkenylated benzamides. The methodology was also extended towards the synthesis of isoquinoline alkaloids derivatives viz. oxyavicine and a dipeptide. The developed protocol is simple and cheap, avoids tedious workup procedures and works efficiently under MW irradiation. (Figure presented.). ispartof: Advanced Synthesis & Catalysis vol:360 issue:16 pages:3083-3089 status: published

Coumarin derivatives possess a wide range of biological activities. By functionalization of the parent coumarin skeleton that has neither antioxidant nor biological activity, a series of new bio-antioxidants has been designed.; Results: New antioxidant compositions (equimolar binary and ternary mixtures) of eight 4-methylcoumarins and three related compounds have been tested and different effects between individual components have been observed: synergism (positive effect), additivism (summary effect) and antagonism (negative effect). Higher oxidative stability of the lipid substrate was obtained in the presence of the new antioxidant compositions of the studied compounds with dl-α-tocopherol and l-ascorbic acid. The role of each component in the antioxidant compositions of ternary mixtures has been identified by using new equations composed by the authors.; Conclusion: All ternary mixtures demonstrate synergism as a result of continuous regeneration of dl-α-tocopherol from the studied antioxidants and l-ascorbic acid. Theoretical calculations have been probed as indicators of the expected effects between the individual components in a binary mixture. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

In this study, novel α-truxillic and β-truxinic acid-based, bio-derived diesters have been developed as internal donors for preparing Ziegler-Natta (ZN) catalysts. Impacts of these bio-derived diesters were investigated on the chemical composition, the morphology, the mode of adsorption, and the propylene polymerization performance of the catalysts in comparison to the most widely used fourth-generation catalyst containing dibutyl phthalate. The molecular structures of the diesters and the particle morphology of the catalysts were preserved in the catalyst preparation. The bio-derived diesters afforded ZN catalysts with a reasonable activity and stereospecificity in propylene polymerization along with similarly broad molecular weight distribution (MWD) as the phthalate-based catalyst. Another promising feature of the catalysts was an opposite hydrogen response in terms of expansion of MWD upon the addition of H2.

Background As of May 2, 2021, U.S. nursing homes (NHs) have reported >651,000 COVID-19 cases and >132,000 deaths to CDC’s National Healthcare Safety Network. Since U.S. COVID-19 vaccination coverage is increasing, we investigate the role of vaccination in controlling future COVID-19 outbreaks. Methods We developed a stochastic, compartmental model of SARS-CoV-2 transmission in a theoretical 100-bed NH with a staff of 99 healthcare personnel (HCP) in a community of 20,000 people. We modeled admission and discharge of residents (parameterized with Centers for Medicare & Medicaid Services data), assuming the following: temporary replacement of HCP when tested positive; daily visits to NH residents; isolation of COVID-19 positive residents; personal protective equipment (PPE) use by HCP; and symptom-based testing of residents and staff plus weekly asymptomatic testing of HCP and facility-wide outbreak testing once a COVID-19 case is identified. We systematically varied coverage of an mRNA vaccine among residents and HCP, and in the community. Simulations also varied PPE adherence, defined as the percentage of time in the facility that HCP properly used recommended PPE (25%, 50% or 75% of the time). Infection was initialized in the community with 40 infectious cases, and initial infection in the NH was allowed after 14 days of vaccine dose 1. Simulations were run for 6 months after dose 2 in the NH. Results were summarized over 1000 simulations. Results At 60% community coverage, expected cumulative symptomatic resident cases over 6 months were ≤5, due to low importation of COVID-19 infection from the community, with further reduction at higher coverage among HCP (Figure 1). Uncertainty bounds narrowed as NH resident coverage or PPE adherence increased. Results were similar if testing of staff and residents stopped. Probability of an outbreak within 4 weeks of dose 2 remained below 5% with high community coverage (Figure 2). Figure 1. Drop in symptomatic cases in nursing home (NH) residents with rise in COVID-19 vaccine coverage in the community, increase in personal protective equipment (PPE) adherence, or increase in coverage among NH residents. In each panel, we plotted the mean number of cumulative symptomatic cases of COVID-19 in NH residents after 6 months since vaccine dose 2 (given 28 days after dose 1) and their 90% confidence interval (CI) for three healthcare personnel (HCP) coverage scenarios: 40%, 60%, or 80%. Coverage in HCP was independently modeled of community coverage. The top row is for NH resident coverage of 65%, the middle for 75%, and the bottom row for 85%. The columns (left to right) are for facility-level PPE adherence of 25% (low adherence), 50% (intermediate adherence), and 75% (high adherence). Weekly asymptomatic testing of HCP and twice-weekly outbreak testing in the facility were modeled with an assumed point-of-care test sensitivity of 80% (symptomatic persons) and 60% (asymptomatic persons) and with specificity of 100% and test turnaround time of 15 minutes. Figure 2. Probability of a COVID-19 outbreak in a nursing home (NH) decreased with increase in vaccine coverage in the community or in healthcare personnel (HCP). An outbreak is defined as an occurrence of 2 or more cases within 4 weeks of dose 2. Probability of no outbreak was calculated by counting how many simulations out of a total of 1000 simulations had ≤1 symptomatic case in NH residents or HCP within 4 weeks after dose 2 was administered in the nursing home. The first vaccine dose in residents and HCP was assumed to be given on day 1, and the second dose 28 days later. A probability value and its 90%-confidence interval (CI) at a given community and HCP coverage was calculated by pooling model outputs for 9 sets (3 PPE adherence values X 3 resident coverage levels) of model simulations. Simulations were performed assuming no asymptomatic testing or facility-wide outbreak testing. Conclusion Results suggest that increasing community vaccination coverage leads to fewer infections in NH residents. Testing asymptomatic residents and staff may have limited value when vaccination coverage is high. High adherence to recommended PPE may increase the likelihood that future COVID-19 outbreaks can be contained. Disclosures John A. Jernigan, MD, MS, Nothing to disclose

Never-ending effort to develop new treatments for malaria, targeting the hemoglobin-degradation in the food vacuole of the parasite is of particular interest because it appears to be critical for the erythrocytic stage parasite development. The Plasmodium aspartic proteinases plasmepsins and cysteine proteases falcipains have been shown to be the major hemoglobin-degrading proteases and are proposed as the high priority drug targets by the World Health Organization for developing novel small molecules as inhibitors of hemoglobin degradation. In the present study, several piperidine and piperazine-based chalcones were assessed for anti-malarial activity against the chloroquine-susceptible P. falciparum 3D7 strain and inhibition of plasmepsin II and falcipain-2. Degradation of hemoglobin by falcipain-2 in the presence or absence of inhibitors was also demonstrated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The IC50 values of chalcones for cell growth inhibition were in the range of 1.60-153.51 μM. IC50 values for cytotoxicity of selected chalcones against Michigan Cancer Foundation (MCF) 7 human breast adenocarcinoma cells were in the range of 8.46-15.64 μM. Molecular docking studies revealed the binding orientation of these chalcones in the active sites of falcipain-2. Our results clearly depict the advantage of these chalcones as they kill P. falciparum malaria parasite in culture, most likely via inhibition of falcipain.

A library of novel 1, 2, 4-oxadiazole linked coumarin dyes have been synthesised via condensation of corresponding acid 6 and N ’-hydroxybenzimidamide 8 . This new class of organic compounds were examined for their fluorescent properties and found to emit blue light in the visible region of the spectrum with very high Stoke's shift values. Most of these compounds demonstrated high quantum yields and fluorescence life time in nano -second range which makes them quite lucrative to be used as new fluorescent probes. The highest quantum yield of 0.68 was shown by compound 9j which also shows high Stoke's shift value. The electronic structure of these coumarin-based donor–π–acceptor (D–π–A)-type organic dyes have been examined by Density Functional Theory (DFT). TGA analysis of few of the compounds show that they are stable up to temperature range of 0–245 °C. The synthesised compounds were characterised by NMR and mass spectrometry and the structure of two of these compounds have been confirmed by X-ray crystallography.

An efficient, catalyst-free, microwave-assisted approach has been developed for the synthesis of 2-aryl/alkyl-3-(1H-benzo[d]imidazol-2-yl)-2,3-dihydroquinazolin-4(1H)-one derivatives by condensing 2-aminobenzamides with various aliphatic, aromatic, and heterocyclic aldehydes. This catalyst-free approach exhibited good functional group compatibility and produced the desired products in good to excellent yields in just 10–20 min. This approach can be seen as a better alternative of the metal-catalyzed protocols used for the synthesis of this class of compounds. The formation of desired compound has also been confirmed by X-ray analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An efficient, catalyst free, microwave assisted approach has been developed for the synthesis of 2-aryl/alkyl-3-(1H-benzo[d]imidazol-2-yl)-2,3-dihydroquinazolin-4(1H)-one derivatives by condensing 2-aminobenzamides with various aliphatic, aromatic and heterocyclic aldehydes. This catalyst free approach exhibited good functional group compatibility and produced the desired products in good to excellent yields in just 10-20 minutes. This approach can be seen as a better alternative of the metal catalyzed protocols used for the synthesis of this class of compounds. The formation of desired compound has also been confirmed by X-ray analysis.

Although there is increasing importance placed on the use of mathematical models for the effective design and management of long-term parasite elimination, it is becoming clear that transmission models are most useful when they reflect the processes pertaining to local infection dynamics as opposed to generalized dynamics. Such localized models must also be developed even when the data required for characterizing local transmission processes are limited or incomplete, as is often the case for neglected tropical diseases, including the disease system studied in this work, viz. lymphatic filariasis (LF). Here, we draw on progress made in the field of computational knowledge discovery to present a reconstructive simulation framework that addresses these challenges by facilitating the discovery of both data and models concurrently in areas where we have insufficient observational data. Using available data from eight sites from Nigeria and elsewhere, we demonstrate that our data-model discovery system is able to estimate local transmission models and missing pre-control infection information using generalized knowledge of filarial transmission dynamics, monitoring survey data, and details of historical interventions. Forecasts of the impacts of interventions carried out in each site made by the models estimated using the reconstructed baseline data matched temporal infection observations and provided useful information regarding when transmission interruption is likely to have occurred. Assessments of elimination and resurgence probabilities based on the models also suggest a protective effect of vector control against the reemergence of LF transmission after stopping drug treatments. The reconstructive computational framework for model and data discovery developed here highlights how coupling models with available data can generate new knowledge about complex, data-limited systems, and support the effective management of disease programs in the face of critical data gaps., Author summary As modelling becomes commonly used in the design and evaluation of parasite elimination programs, the need for well-defined models and datasets describing the nature of transmission processes in local settings is becoming pronounced. For many neglected tropical diseases, however, data for site-specific model identification are typically sparse or incomplete. In this study, we present a new data-model computational discovery system that couples data-assimilation methods based on existing monitoring survey data with model-generated data about baseline conditions to discover the local transmission models required for simulating the impacts of interventions in typical endemic locations for the macroparasitic disease, lymphatic filariasis (LF). Using data from eight study sites in Nigeria and elsewhere, we show that our reconstructive computational framework is able to combine information contained within partially-available site-specific monitoring data with knowledge of parasite transmission dynamics embedded in process-based models to generate the missing data required for inducing reliable locally applicable LF models. We also show that the models so discovered are able to generate the intervention forecasts required for supporting management-relevant decisions in parasite elimination.

A novel, rapid, and efficient microwave-assisted, metal-free, base-mediated approach has been developed for the construction of benzimidazo[1,2-a]quinazolines from readily available building blocks. This synthetic strategy affords a diverse range of benzimidazo[1,2-a]quinazoline derivatives in moderate to good yields.

The field of nanoscience has blossomed over the last two decades and the importance of nanotechnology has increased in areas such as computing, sensors, biomedicine, and many other applications. In the present study, recent important advances in the functionalization of graphene with an emphasis on the physical properties upon tailored modification have been reviewed. It has been observed that functionalization cannot only stabilize graphene’s unique properties but also introduce some new properties. The functionalization of graphene can be done with different methods like covalent functionalization, non-covalent functionalization, and with the decoration of nanoparticles. In this study, we put forward functionalization of graphene by polymers with different methods such as by direct linking of polymeric chains to the graphene surface or by the controlled growth of the polymeric chains at graphene surface or by decorating with polymers. The exceptional in-plane properties of graphene that are more complete exfoliation of graphite towards single graphene sheets with excellent mechanical, thermal, electrical, and barrier properties. The biological applications for the treatment of deadly diseases like cancer by functionalized nano-graphene oxide (NGO) have reviewed in depth. The application of NGO for drug delivery for gene therapy treatment has also been discussed in this review.

Botulinum neurotoxins (BoNTs), the most poisonous proteins known to humankind, are a family of seven (serotype A to G) immunologically distinct proteins synthesized primarily by different strains of the anaerobic bacterium Clostridium botulinum. Being the causative agents of botulism, the toxins block neurotransmitter release by specifically cleaving one of the three soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, thereby inducing flaccid paralysis. The development of countermeasures and therapeutics against BoNTs is a high-priority research area for public health because of their extreme toxicity and potential for use as biowarfare agents. Extensive research has focused on designing antagonists that block the catalytic activity of BoNTs. In this study, we screened 300 small natural compounds and their analogues extracted from Indian plants for their activity against BoNT serotype A (BoNT/A) as well as its light chain (LCA) using biochemical and cellular assays. One natural compound, a nitrophenyl psoralen (NPP), was identified to be a specific inhibitor of LCA with an in vitro 50% inhibitory concentration (IC50) value of 4.74 ± 0.03 µM. NPP was able to rescue endogenous synaptosome-associated protein 25 (SNAP-25) from cleavage by BoNT/A in human neuroblastoma cells with an IC50 of 12.2 ± 1.7 µM, as well as to prolong the time to the blocking of neutrally elicited twitch tensions in isolated mouse phrenic nerve-hemidiaphragm preparations. IMPORTANCE The long-lasting endopeptidase activity of BoNT is a critical biological activity inside the nerve cell, as it prompts proteolysis of the SNARE proteins, involved in the exocytosis of the neurotransmitter acetylcholine. Thus, the BoNT endopeptidase activity is an appropriate clinical target for designing new small-molecule antidotes against BoNT with the potential to reverse the paralysis syndrome of botulism. In principle, small-molecule inhibitors (SMIs) can gain entry into BoNT-intoxicated cells if they have a suitable octanol-water partition coefficient (log P) value and other favorable characteristics (P. Leeson, Nature 481:455–456, 2012, https://doi.org/10.1038/481455a). Several efforts have been made in the past to develop SMIs, but inhibitors effective under in vitro conditions have not in general been effective in vivo or in cellular models (L. M. Eubanks, M. S. Hixon, W. Jin, S. Hong, et al., Proc Natl Acad Sci U S A 104:2602–2607, 2007, https://doi.org/10.1073/pnas.0611213104). The difference between the in vitro and cellular efficacy presumably results from difficulties experienced by the compounds in crossing the cell membrane, in conjunction with poor bioavailability and high cytotoxicity. The screened nitrophenyl psoralen (NPP) effectively antagonized BoNT/A in both in vitro and ex vivo assays. Importantly, NPP inhibited the BoNT/A light chain but not other general zinc endopeptidases, such as thermolysin, suggesting high selectivity for its target. Small-molecule (nonpeptidic) inhibitors have better oral bioavailability, better stability, and better tissue and cell permeation than antitoxins or peptide inhibitors.

Malaria, particularly in endemic countries remains a threat to the human health and is the leading the cause of mortality in the tropical and sub-tropical areas. Herein, we explored new C2 symmetric hydroxyethylamine analogs as the potential inhibitors of Plasmodium falciparum (P. falciparum; 3D7) in in-vitro cultures. All the listed compounds were also evaluated against crucial drug targets, plasmepsin II (Plm II) and IV (Plm IV), enzymes found in the digestive vacuole of the P. falciparum. Analog 10f showed inhibitory activities against both the enzymes Plm II and Plm IV (Ki, 1.93 ± 0.29 µM for Plm II; Ki, 1.99 ± 0.05 µM for Plm IV). Among all these analogs, compounds 10g selectively inhibited the activity of Plm IV (Ki, 0.84 ± 0.08 µM). In the in vitro screening assay, the growth inhibition of P. falciparum by both the analogs (IC50, 2.27 ± 0.95 µM for 10f; IC50, 3.11 ± 0.65 µM for 10g) displayed marked killing effect. A significant growth inhibition of the P. falciparum was displayed by analog 12c with IC50 value of 1.35 ± 0.85 µM, however, it did not show inhibitory activity against either Plms. The hemolytic assay suggested that the active compounds selectively inhibit the growth of the parasite. Further, potent analogs (10f and 12c) were evaluated for their cytotoxicity towards mammalian HepG2 and vero cells. The selectivity index (SI) values were noticed greater than 10 for both the analogs that suggested their poor toxicity. The present study indicates these analogs as putative lead structures and could serve as crucial for the development of new drug molecules.

A new class of chiral phthalimides functionalized with aryl piperazines was designed anticipating their strong candidature for crystal engineering and technological applications. Five new phthalimides were synthesized, characterized and subjected to single crystal X-ray diffraction study that directed their non-centrosymmetric structures. Four phthalimides crystallized in P21 space group with monoclinic crystal system, however, one was found to possess P212121 space group with orthorhombic system. The supramolecular architectures of phthalimide crystals were analysed by an approach based on consideration of energy of intermolecular interaction. The molecular hyperpolarizability (β) calculation for all the listed phthalimides indicated their promising candidature for NLO materials. Further, the crystalline form of all phthalimides was evaluated for their second harmonic generation (SHG) response. A significant response of 16.4 mV was measured for phthalimide possessing t-butyl substituent at the para position of 4-benzylpiperazine. This high SHG response may be attributed to the molecular chirality and helical supramolecular frameworks stabilized by C-H ⋯O hydrogen bonds in the solid state. The current study attests chiral phthalimides possessing arylpiperazines as effective nominees to the area of crystal engineering and nonlinear optics.

A microwave-assisted highly efficient intermolecular domino carbopalladation/C-H functionalization sequence has been developed to access bis-heteroaryl frameworks in a single operation. The reaction involves carbopalladation of the halogenated acrylamides or phenylpropiolamides by the Pd(0) catalysis, followed by the direct (hetero)arylation to give products with good to excellent yields. The synthetic utility of this method was also extended towards the application of the Ugi-adduct as the starting material.