Synthesis, Crystal Structure, DFT Calculations, Hirshfeld Surface Analysis and In Silico Drug-Target Profiling of (R)-2-(2-(1,3-Dioxoisoindolin-2-yl)propanamido)benzoic Acid Methyl Ester.

The work here reflects synthesis, DFT studies, Hirshfeld charge analysis and crystal data exploration of pharmacologically important (R)-2-(2-(1,3-dioxoisoindolin-2-yl)propanamido)benzoic acid methyl ester (5) to understand its properties for further chemical transformations. The methyl anthranilate (2) was produced by the esterification of anthranilic acid in an acidic medium. The phthaloyl-protected alanine (4) was rendered by the fusion of alanine with phthalic anhydride at 150 °C, followed by coupling with (2) furnished isoindole (5). The characterization of products was performed using IR, UV-Vis, NMR and MS. Single-crystal XRD also verified the structure of (5) in which N-H⋯O bonding stabilizes the molecular configuration of (5), resulting in the formation of S(6) hydrogen-bonded loop. The molecules of isoindole (5) are connected in the form of dimers, and the π⋯π stacking interaction between aromatic rings further stabilizes the crystal packing. DFT studies suggest that HOMO is over the substituted aromatic ring, the LUMO is present mainly over the indole side, and nucleophilic and electrophilic corners point out the reactivity of the product (5). In vitro and in silico analysis of (5) shows its potential as an antibacterial agent targeting DNA gyrase and Dihydroorotase from E. coli and tyrosyl-tRNA synthetase and DNA gyrase from Staphylococcus aureus.

Correction to: An efficient protocol for the synthesis of highly sensitive indole imines utilizing green chemistry: optimization of reaction conditions.

In the original publication, one of the co-authors name Sana Jamshaid was missed out. The correct authors' group is updated in this correction.

An efficient protocol for the synthesis of highly sensitive indole imines utilizing green chemistry: optimization of reaction conditions.

Novel and highly sensitive indole-based imines have been synthesized. Their synthesis has been compared employing a variety of protocols. Ultimately, a convenient, economical and high yielding set of conditions employing green chemistry have been designed for their synthesis.

Stereoselective synthesis of (3R)-3-alkyl-4,1-benzoxazepine-2,5-diones.

Novel 3-alkyl-4,1-benzoxazepine-2,5-diones were synthesized in good ee exploiting the chiral pool methodology, an economical way of asymmetric synthesis. Various anthranilic acids are coupled with different α-haloacids to afford N-acylated anthranilic acid intermediates which undergo cyclization to (3R)-3-alkyl-4,1-benzoxazepines-2,5-diones.

Asymmetric synthesis of 4,1-benzoxazepine-2,5-diones--effect of the halogen of (2S)-α-haloacids.

Novel chiral 4,1-benzoxazepine-2,5-diones have been unusually synthesized in a single step by exploiting the chiral pool methodology. Substituted anthranilic acids afford N-acylanthranilic acids and (3R)-3-alkyl-4,1-benzoxazepines-2,5-dione upon coupling with α-chloroacids or α-bromoacids, respectively.

4-Chloro-2-hy-droxy-N-(4-methyl-phen-yl)benzamide.

In the title compound, C(14)H(12)ClNO(2), the dihedral angle between the aromatic rings is 14.87 (11)° and an intra-molecular N-H⋯O hydrogen bond generates an S(6) ring. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, generating C(6) chains propagating along the c-axis direction.

Population dynamics of pelagic rotifers in Marala Headworks (Pakistan).

Research work was designed to investigate the density and diversity of pelagic rotifers in a Lake near Marala Headworks. The physico-chemical parameters of water such as pH, dissolved oxygen, temperature, electrical conductivity, transparency and turbidity were evaluated. Correlation between rotifers and these parameters was also studied. Plankton sampling was done on monthly basis in order to check the population density of rotifers. In total, 18 species of rotifers were identified which belonged to 11 genera. The highest number of rotifers and their diversity was shown by genera namely Brachionus, Keratella, and Filinia. The Brachionus calyciflorus was dominant species in all the samples with mean population density (41%). Analysis of variance of physico-chemical parameters presented that the air and water temperature, electrical conductivity, transparency, dissolved oxygen and oxygen saturation were statistically significant in all the months. While pH was statistically non-significant (p≥0.05. Pearson correlation showed that oxygen and transparency were negatively correlated with rotifers density and diversity. Air and water temperature, concentration of hydrogen ions (pH), electrical conductivity and salinity showed positive relationship with density and diversity of rotifers.

DNA Barcoding: Molecular Identification and Phylogenetic Analysis of Pheretimoid Earthworm (Metaphire sp. and Amynthas sp.) Based on Mitochondrial Partial COI Gene from Sialkot, Pakistan.

The extremely difficult and challenging process is identifying pheretimoid species, genus Metaphire and Amynthas involving increased homoplasy in various morphological characteristics. The molecular identification, phylogenetic relationships, and evolutionary divergence time of earthworms belonging to the pheretimoid complex were investigated in this study using partial mitochondrial COI (cytochrome C oxidase subunit I) gene sequences ranging from 550-680 bp. Results revealed that 86 pheretimoid earthworms were morphologically different from a total of 342 mature worms. Moreover, 11 pheretimoid species were molecularly identified, including Metaphire posthuma (02), M. anomala (01), M. houlleti (02), M. californica (01), M. birmanica (02), Amynthas minimus (01), A. morrisi (01), and M. bununa (01). A phylogenetic tree was constructed with bootstrap values of 95%, which supported a monophyletic lineage of two well-supported clades formed by 12 partial COI sequences and 48 GenBank sequences using Hirudo medicinalis as an outgroup. The monophyly of these obtained genera indicated overall similarity at species level. Today, species like Amynthas, Metaphire and Pheretima have worm diversity in the form of pheretimoid earthworms, which dates to the Late Miocene (11.2-5.3 Mya) and the Pliocene (5.3-2.4 Mya). Compared to all relevant pheretimoid species, genetic p-distance values ranged from 0.0% to 0.57% (less than 1%). These low range values demonstrated that both genera Metaphire and Amynthas, supported the theory, which states that there are shared similarities among the species, despite different morphology. The current study is the first attempt in Pakistan to identify earthworms through DNA barcoding thus providing a genomic stamp. The work explored the significance of COI gene sequences to construct molecular tools that will be useful to overcome the different obstacles in morphologically similar earthworm identification and their phylogenetic study.

2-Hy-droxy-N-(4-methyl-phen-yl)benzamide.

In the crystal structure of the title compound, C(14)H(13)NO(2), the mol-ecules are approximately planar, the r.m.s. deviation for all non-H atoms being 0.0435 Å; the dihedral angle between the two rings is 3.45 (12)°. The planarity is accounted for in terms of the presence of intra-molecular N-H⋯O and C-H⋯O hydrogen bonding, each of which completes an S(6) ring motif. The mol-ecules are stabilized in the form of supra-molecular chains extending along the crystallographic c axis due to inter-molecular O-H⋯O and C-H⋯O hydrogen bonding; each type leads to an R(2) (1)(6) ring motif.

2-Hy-droxy-5-nitro-N-phenyl-benzamide.

The mol-ecule of the title compound, C(13)H(10)N(2)O(4), is almost planar with a dihedral angle between the benzene rings of 1.99 (13)°. The nitro group and its parent benzene ring are oriented at a dihedral angle of 7.6 (3)°. Intra-molecular C-H⋯O and N-H⋯O hydrogen bonds form two planar S(6) motifs. Inter-molecular O-H⋯O=C hydrogen bonds join mol-ecules into chains extending along the c axis.

2-Hy-droxy-N-(3-nitro-phen-yl)benzamide.

In the crystal structure of title compound, C(13)H(10)N(2)O(4), as expected, the nitro- and hy-droxy-substituted benzene rings are planar with r. m. s. deviations of 0.0037 and 0.0014 Å, respectively, but are twisted slightly relative to each other, making a dihedral angle of 12.23 (7)°. The nitro group is only slightly twisted [by 2.71 (16)°] with respect to its parent ring. An intra-molecular N-H⋯O hydrogen bond forms an S(6) ring motif. Inter-molecular N-H⋯O and O-H⋯O hydrogen bonds build up sheets parallel to the ab plane. Futhermore, weak π-π inter-actions [centroid-centroid distances = 3.7150 (8) 3.7342 (6) and 3.9421 (8) Å] between the rings yield a three-dimensional network.

5-Chloro-2-hy-droxy-benzoic acid.

The asymmetric unit of the title compound, C(7)H(5)ClO(3), contains two mol-ecules; both feature an intra-molecular O-H⋯O hydrogen bond, which generates an S(6) ring. In the crystal, both mol-ecules form inversion dimers linked by pairs of O-H⋯O hydrogen bonds with R(2) (2)(8) ring motifs. The dimers are inter-linked by C-H⋯O inter-actions.

N-(4-Chloro-phen-yl)-2-hy-droxy-benzamide.

In the title compound, C(13)H(10)ClNO(2), the dihedral angle between the aromatic rings is 20.02 (6)° and intra-molecular N-H⋯O and C-H⋯O hydrogen bonds both generate S(6) rings. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds into C(6) chains propagating in [010].

N-(3-Chloro-phen-yl)-2-hy-droxy-benzamide.

In the title compound, C(13)H(10)ClNO(2), the dihedral angle between the aromatic rings is 5.57 (9)° and intra-molecular N-H⋯O and C-H⋯O hydrogen bonds both generate S(6) rings. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds into C(6) chains propagating along [010]. Mol-ecules from neighbouring chains along the z axis are involved in C-H⋯π and π-π stacking inter-actions [centroid-centroid distance = 3.9340 (10) Å].

A facile microwave assisted synthesis and structure elucidation of (3R)-3-alkyl-4,1-benzoxazepine-2,5-diones by crystallographic, spectroscopic and DFT studies.

The use of microwave (MW) irradiation in organic synthesis has become increasingly popular within the pharmaceutical and academic arenas because it is a new enabling technology for drug discovery and development. It is a rapid way of synthesis, which involves faster reaction rates and high selectivity to conventional heating method of syntheses. The MW-assisted 7-exo-tet cyclization of N-acylanthranilic acids afforded (3R)-3-alkyl-4,1-benzoxazepines-2,5-diones in very short duration (20 min) with extraordinary high yields in comparison to conventional heating mode of synthesis. The method development, comparative yields of MW-assisted and thermal method of syntheses, crystallographic, spectroscopic and density functional theory (DFT) studies are reported herein. Four novel compounds with chemical formulas C10H9BrClNO35m, C19H19NO36e, C13H14ClNO36h and C12H11Br2NO36h were synthesized, validated by 1HNMR, 13CNMR, FT-IR, UVVis, EIMS spectroscopic techniques and confirmed by using single crystal X-ray diffraction (SC-XRD) study. The DFT and TDDFT calculations at B3LYP/6-311 + G(d,p) level of theory were performed for comparative analysis of spectroscopic data, optimized geometries, frontier molecular orbitals (FMOs), natural bond orbital (NBO) analysis and nonlinear optical (NLO) properties of 5m, 6e, 6h and 6o. Overall, experimental findings were supported nicely by corresponding DFT computed results. The NBO analysis confirmed that the presence of non-covalent interactions, hydrogen bonding and hyper- conjugative interactions are pivotal cause for the existence of 5m, 6e, 6h and 6o in the solid-state. NLO analysis showed that 5m, 6e, 6h and 6o have significant NLO properties as compared to prototype standard compound which disclosed their potential for technology related applications.

2-Hydr-oxy-5-nitro-benzamide.

In the title compound, C(7)H(6)N(2)O(4), an intra-molecular O-H⋯O hydrogen bond generates an S(6) ring. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds occur. Weak C-H⋯O links consolidate the packing, leading to R(2) (1)(7) and R(2) (2)(10) loops within (100) polymeric sheets.

2-Hydr-oxy-3-nitro-benzamide.

The asymmetric unit of title compound, C(7)H(6)N(2)O(4), contains two mol-ecules, one of which has a disordered nitro group with an occupancy ratio of 0.517 (9):0.483 (9) for the O atoms. Both mol-ecules contain an intra-molecular O-H⋯O hydrogen bond. In the crystal, both mol-ecules form inversion dimers linked by pairs of N-H⋯O hydrogen bonds, resulting in R(2) (2)(8) ring motifs. The dimers are connected by further N-H⋯O links and weak C-H⋯O inter-actions, resulting in a layered motif.

2-Hydr-oxy-3-nitro-N-phenyl-benzamide.

The asymmetric unit of the title compound, C(13)H(10)N(2)O(4), contains two crystallographically independent mol-ecules. The aromatic rings are oriented at dihedral angles of 24.39 (3) and 7.47 (3)° in the two mol-ecules and intra-molecular N-H⋯O and O-H⋯O hydrogen bonds result in the formation of two planar six-membered rings. In the crystal structure, inter-molecular O-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into chains, forming R(2) (2)(10) ring motifs. Weak π-π contacts between the benzene and phenyl rings [centroid-centroid distance = 3.955 (3) Å] may further stabilize the structure.