Divergent Synthesis of Pyrazoles via Manganese Pincer Complex Catalyzed Acceptorless Dehydrogenative Coupling Reactions.

This report detailed the synthesis of multi-substituted pyrazoles through the acceptorless dehydrogenative coupling (ADC) reaction catalyzed by a well-defined manganese(I)-pincer complex. Symmetrically substituted pyrazoles were synthesized by reacting 1,3-diols with hydrazines. Unsymmetrically substituted pyrazoles were selectively made via the ADC of primary alcohols with methyl hydrazones. Water and hydrogen are liberated as the green byproducts. The endurance of these methodologies has been presented by producing 30 substrates with varied functionalities. Model reactions were scaled up to demonstrate practicability. The reaction rate and order were measured to transparent the involvement of the reagents during catalysis. Control experiments elucidated the plausible reaction mechanisms.

Catalytic acceptorless dehydrogenative borylation of styrenes enabled by a molecularly defined manganese complex.

In this study, we employed a 3d metal complex as a catalyst to synthesize alkenyl boronate esters through the dehydrogenative coupling of styrenes and pinacolborane. The process generates hydrogen gas as the sole byproduct without requiring an acceptor, rendering it environmentally friendly and atom-efficient. This methodology demonstrated exceptional selectivity for dehydrogenative borylation over direct hydroboration. Additionally, it exhibited a preference for borylating aromatic alkenes over aliphatic ones. Notably, derivatives of natural products and bioactive molecules successfully underwent diversification using this approach. The alkenyl boronate esters served as precursors for the synthesis of various pharmaceuticals and potential anticancer agents. Our research involved comprehensive experimental and computational studies to elucidate the reaction pathway, highlighting the B-H bond cleavage as the rate-determining step. The catalyst's success was attributed to the hemilability and metal-ligand bifunctionality of the ligand backbone.

Visiblelight-induced ternary electron donor-acceptor complex enabled synthesis of 2-(2-hydrazinyl) thiazole derivatives and the assessment of their antioxidant and antidiabetic therapeutic potential.

A mild and eco-friendly visible-light-induced synthesis of 2-(2-hydrazinyl) thiazole from readily accessible thiosemicarbazide, carbonyl, and phenacyl bromide in the absence of a metal catalyst and/or any extrinsic photosensitizer is reported. This approach only requires a source of visible light and a green solvent at room temperature to produce the medicinally privileged scaffolds of hydrazinyl-thiazole derivatives in good to outstanding yields. Experimental studies support the in situ formation of a visible-light-absorbing, photosensitized colored ternary EDA complex. The next step is to prepare a pair of radicals in an excited state, which makes it easier to prepare thiazole derivatives through a SET and PCET process. DFT calculations additionally supported the mechanistic analysis of the course of the reaction. The antioxidant and antidiabetic properties of some of the compounds in the synthesized library were tested in vitro. All the investigated compounds demonstrated appreciable antioxidant activity, as evidenced by the reducing power experiment and the IC50 values of the DPPH radical scavenging experiment. Furthermore, the IC50 values for 4c, 4d, and 4g also demonstrated a strong α-amylase inhibitory effect.

Ruthenium-Catalyzed Reductive Coupling of Epoxides with Primary Alcohols via Hydrogen Transfer Catalysis.

Herein, we report the ruthenium-catalyzed synthesis of ß-alkylated secondary alcohols via the regioselective ring-opening of epoxides with feedstock primary alcohols. The reaction utilized alcohol as the carbon source and the terminal reductant. Kinetic and labeling experiments elucidate the hydrogen transfer catalysis that operates via tandem Markovnikov selective transfer hydrogenation of terminal epoxides and hydrogen transfer-mediated cross-coupling of the resulting alcohol with primary alcohol substrates. A broad scope (40 examples including drugs/natural product derivatives) and excellent regioselectivity for a variety of substrates were shown.

Influence of Triazole Substituents of Bis-Heteroleptic Ru(II) Probes toward Selective Sensing of Dihydrogen Phosphate.

A series of seven new bis-heteroleptic Ru(II) probes (1[PF6]2-7[PF6]2) along with two previously reported probes (8[PF6]2 and 9[PF6]2) containing a similar anion binding triazole unit (hydrogen bond donor) functionalized with various substituents are employed in a detailed comparative investigation for the development of superior selective probes for H2PO4-. Various solution- and solid-state studies, such as 1H-DOSY NMR, dynamic light scattering (DLS), single-crystal X-ray crystallography, and transmission electron microscopy (TEM), have established that the selective sensing of H2PO4- by this series of probes is primarily due to supramolecular aggregation driven enhancement of 3MLCT emission. Intestingly, 1[PF6]2 and 7[PF6]2, having an electron-deficient (π-acidic) aromatic pentafluorophenyl substituent are found to be superior probes for H2PO4- in comparison to the other aryl- and polyaromatic-substituted analogues (2[PF6]2-6[PF6]2, 8[PF6]2, and 9[PF6]2), in terms of a higher enhancement of the 3MLCT emission band, a greater binding constant, and a lower detection limit. The superiority of 1[PF6]2 and 7[PF6]2 could be due to better supramolecular aggregation properties in the cases of pentafluorophenyl analogues via both hydrogen bonding and anion-fluorine/anion-π noncovalent interactions.

Cu(II)-Metallacryptands Self-Assembled to Vesicular Aggregates Capable of Encapsulating and Transporting an Anticancer Drug Inside Cancer Cells.

Crystallographically characterized M2 L4 type cationic Cu(II)-metallacryptands [MC(X)] derived from a series of bis-pyridyl-bis-urea ligands (LX ; X = O, S, C) are self-assembled to single-layered vesicular aggregates in DMSO, DMSO/water, and DMSO/DMEM (biological media). One such vesicle is MC(O)-vesicle that is demonstrated to be able to load and release (pH responsive) an anticancer drug, namely doxorubicin hydrochloride (DOX). DOX-loaded MC(O)-vesicle is also successfully transported within MDA-MB-231 cells-a highly aggressive human breast cancer cell line. Such self-assembling behavior to form vesicular aggregates by metallacryptands (MCs) is hitherto unknown.

Design and Synthesis of ZnII -Coordination Polymers Anchored with NSAIDs: Metallovesicle Formation and Multi-drug Delivery.

A series of coordination polymers synthesized from a bis-pyridyl linker, namely 4,4'-azopyridine (L), selected non-steroidal-anti-inflammatory drugs (NSAIDs), namely diclofenac (Dic), ibuprofen (Ibu), flurbiprofen (Flu), mefenamic acid (Mefe), and naproxen (Nap), and Zn(NO3 )2 were characterized by single crystal X-ray diffraction. One of the coordination polymers, namely CP3 derived from Flu, was able to form metallovesicles in DMSO, DMSO/H2 O and DMSO/DMEM (biological media) as revealed by TEM, AFM and DLS. Metallovesicle formation by CP3 was further supported by loading a fluorescent dye, namely calcein, as well as an anti-cancer drug, doxorubicin hydrochloride (DOX), as revealed by UV-vis and emission spectra, and fluorescence microscopy. DOX-loaded metallovesicles of CP3 (DOX@CP3-vesicle) could be delivered in vitro to a highly aggressive human breast cancer cell line, namely MDA-MB-231, as revealed by MTT and cell migration assays, and also cell imaging performed under laser scanning confocal microscope (LSCM). Thus, a proof of concept for developing a multi-drug delivery system derived from a metallovesicle for delivering an anti-cancer drug to cancer cells is demonstrated for the first time.

Self-Assembly of Spherical Organic Molecules to Form Hollow Vesicular Structures in Water for Encapsulation of an Anticancer Drug and Its Release.

Developing hierarchical supramolecular structures is important for better understanding of various biological functions and possibly generating new materials for biomedical applications. Herein, we report the first examples of functional vesicles derived from cationic spherical organic molecules (C1 -C3 ) which were readily synthesized by reacting a C3 -symmetric tris-benzimmidazole derivative (possessing a 1,3,5-ethyl substituted aromatic core) with 1,3,5-substituted tris-bromomethyl benzene derivatives. Vesicle formation by C1 -C3 was probed by high-resolution microscopy (TEM and AFM), dynamic light scattering (DLS) and fluorescence microscopic imaging of calcein-loaded vesicles. One of the vesicles [Vesicle(C3 )] displayed the ability to load the anticancer drug doxorubicin (DOX). The drug was subsequently released from DOX@Vesicle(C3 ) in a stimuli-responsive manner in presence of the well-known vesicle destroyer Triton X-100, as revealed by in vitro cell migration assay carried out on a highly aggressive human breast cancer cell line (MDA-MB-231).

Rational Approach Towards Designing Metallogels From a Urea-Functionalized Pyridyl Dicarboxylate: Anti-inflammatory, Anticancer, and Drug Delivery.

A structural rationale was adopted to design a series of metallogels from a newly synthesized urea-functionalized dicarboxylate ligand, namely, 5-[3-(pyridin-3-yl)ureido]isophthalic acid (PUIA), that produces metallogels upon reaction with various metal salts (CuII , ZnII , CoII , CdII , and NiII salts) at room temperature. The gels were characterized by dynamic rheology and transmission electron microscopy (TEM). The existence of a coordination bond in the gel state was probed by FTIR and 1 H NMR spectroscopy in a ZnII metallogel (i.e., MG2). Single crystals isolated from the reaction mixture of PUIA and CoII or CdII salts characterized by X-ray diffraction revealed lattice inclusion of solvent molecules, which was in agreement with the hypothesis based on which the metallogels were designed. MG2 displayed anti-inflammatory response (prostaglandin E2 assay) in the macrophage cell line (RAW 264.7) and anticancer properties (cell migration assay) on a highly aggressive human breast cancer cell line (MDA-MB-231). The MG2 metallogel matrix could also be used to load and release (pH responsive) the anticancer drug doxorubicin. Fluorescence imaging of MDA-MB-231 cells treated with MG2 revealed that it was successfully internalized.

Rationally Developed Metallogelators Derived from Pyridyl Derivatives of NSAIDs Displaying Anti-Inflammatory and Anticancer Activities.

Metal-ligand coordination involving hydrogen-bond-functionalized ligands was employed rationally to get an easy access to a series of metallogelators derived from 3-pyridyl derivatives of nonsteroidal anti-inflammatory drugs [e.g., ibuprofen, sulindac, and flurbiprofen designated as 3-pyIBU, 3-pySUL, and 3-pyFLR, respectively] and biogenic metal centers [Zn(II), Cu(II), Mn(II), and Ag(I)]. A total of 13 metallogels (MG1-MG13) were obtained by allowing the ligands and the metal salts to react in dimethyl sulfoxide (DMSO)/water at room temperature. A slightly different solvent system (DMSO/water/MeOH) afforded four crystalline coordination complexes of 3-pyIBU, namely, [{Cu(3-pyIBU)4(DMSO)2}(NO3)2] (CC1), [{Ag(3-pyIBU)2}(BF4)] (CC2), [{Ag(3-pyIBU)2}(ClO4)] (CC3), and [{Cu(3-pyIBU)4(CH3OH)2}(OTf)] (CC4), which were fully characterized by single-crystal X-ray diffraction. However, none of these coordination complexes produced metallogels-the results corroborated well with the rationale, based on which the metallogelators were obtained. Two selected metallogels (MG3 and MG9) could be leached out from the corresponding metallogels to the bulk solvent to the extent of 51 and 59%, respectively after 24 h of incubation at 37 °C, indicating their plausible use in topical application. Moreover, one of the selected metallogelators, i.e., MG9, displayed anti-inflammatory response and was able to inhibit the migration of highly aggressive human breast cancer cells MDA-MB-231, suggesting its plausible use as anticancer agent.

Exfoliated Nanosheets of a CuII Coordination Polymer Modulate Enzyme Activity of α-Chymotrypsin.

A 2D coordination polymer derived from 5-azidoisophthalic acid (AIA) and Cu(NO3 )2 was designed with the aim of modulating the activity of a digestive enzyme α-chymotrypsin (ChT). The coordination polymer namely {[Cu0.5 (µ-AIA)0.5 (H2 O)]⋅2 H2 O}α (CP1) was successfully synthesized and fully characterized by single-crystal X-ray diffraction (SXRD). An exfoliated nanosheet (ENS) of CP1 was readily produced by overnight stirring of hand-ground CP1 crystals dispersed in DMSO. ENS(CP1) was demonstrated to be acting as an inhibitor of ChT; as much as ≈97 % inhibition of ChT was achieved with 100 µm of ENS(CP1) using N-succinyl-l-phenylalanine-p-nitroanilide (SPNA) as substrate. Enzyme kinetics data revealed that the inhibition of ChT followed a competitive pathway. An enzyme assay under varying ionic strength and varying concentration of free histidine revealed that the active site His-57 participated in coordination with the CuII metal center of ENS(CP1) thereby preventing the substrate (SPNA) from binding with the enzyme resulting in efficient inhibition.

Supramolecular Hydrogel Derived from a C3-Symmetric Boronic Acid Derivative for Stimuli-Responsive Release of Insulin and Doxorubicin.

A C3-symmetric triazine based triboronic acid (HG1) was designed and synthesized. HG1 was found to give hydrogel in DMSO-water (1:9). The hydrogel was rheo-reversible and thermoreversible over a few cycles. Single-crystal X-ray diffraction (SXRD) studies on the crystals of HG1 established the presence of honeycomb network in which solvent molecules (DMSO and water) were occluded. SXRD data corroborated well with the hypothesis based on which HG1 was designed. Stimuli responsive release (in vitro) of insulin and doxorubicin from the hydrogel was also achieved.

Hand-Ground Nanoscale ZnII -Based Coordination Polymers Derived from NSAIDs: Cell Migration Inhibition of Human Breast Cancer Cells.

Increased levels of intracellular prostaglandin E2 (PGE2 ) have been linked with the unregulated cancer cell migration that often leads to metastasis. Non-steroidal anti-inflammatory drugs (NSAIDs) are known inhibitors of cyclooxygenase (COX) enzymes, which are responsible for the increased PGE2 concentration in inflamed as well as cancer cells. Here, we demonstrate that NSAID-derived ZnII -based coordination polymers are able to inhibit cell migration of human breast cancer cells. Various NSAIDs were anchored to a series of 1D ZnII coordination polymers through carboxylate-Zn coordination, and these structures were fully characterized by single-crystal X-ray diffraction. Hand grinding in a pestle and mortar resulted in the first reported example of nanoscale coordination polymers that were suitable for biological studies. Two such hand-ground nanoscale coordination polymers NCP1 a and NCP2 a, which contained naproxen (a well-studied NSAID), were successfully internalized by the human breast cancer cells MDA-MB-231, as was evident from cellular imaging by using a fluorescence microscope. They were able to kill the cancer cells (MTT assay) more efficiently than the corresponding mother drug naproxen, and most importantly, they significantly inhibited cancer cell migration thereby displaying anticancer activity.

A case of symptomatic tailgut duplication cyst(retro-rectal cystic hamartoma) in an adult male.

Tailgut duplication cyst (retro-rectal cystic hamartoma) is a rare congenital developmental lesion arising from post-natal primitive gut remnants. Tailgut cysts are found more commonly in middle-aged females. It may be asymptomatic or symptomatic in complicated cases. Major differentials include epidermoid cyst, dermoid cyst and anterior meningocele. Unfortunately no radiological sign can specifically diagnose it and surgical resection and histopathology remain the cornerstone for diagnosis. Here we present a case of symptomatic tailgut duplication cyst in an adult male.

Congenital in situ malrotation of the liver in an asymptomatic adult: a rare entity.

Congenital malformations of the liver are rare occurrences. We are reporting a case of in situ malrotation of the liver. The patient was asymptomatic and had undergone a non-contrast CT scan of the upper abdomen, which showed malrotation of the liver. The purpose of submitting this case report is to make radiologists and surgeons aware of this unusual anatomical variation. Malrotation of the liver as a part of heterotaxy syndrome or situs ambiguous has been reported, but isolated malrotation of the liver without polysplenia in an adult male is a rare entity. A similar case has been reported in the literature as an incidental autopsy finding. Relevant references to this case are given below.

Multifunctional single-layered vesicles derived from Cu(ii)-metal-organic-polyhedra.

Cu(ii) metal-organic-polyhedra (MOP) derived from a tris-pyridyl ligand gave stable single-layered vesicles capable of encapsulating an anti-cancer drug (doxorubicin - DOX) and its pH responsive release. While encapsulation of DOX was further confirmed by MTT assay and cellular imaging, α-chymotrypsin inhibition assay corroborated well with the single crystal structures of the MOP. The MOP derived vesicles reported herein not only represent the rare examples of such hierarchical architectures derived from MOP but also provide the first example of multifunctional organic-inorganic synthetic bio-membranes.

Nanoscale MnII -Coordination Polymers for Cell Imaging and Heterogeneous Catalysis.

A mixed ligand approach was exploited to synthesize a new series of MnII -based coordination polymers (CPs), namely, CP1 {[Mn(µ-dpa)(µ-4,4'-bp)]⋅MeOH}∞ , CP2 {[Mn3 (µ-dpa)3 (2,2'-bp)2 ]}∞ , CP3 {[Mn3 (µ-dpa)3 (1,10-phen)2 ]⋅2 H2 O}∞ , CP4 {[Mn(µ-dpa)(µ-4,4'-bpe)1.5 ]⋅H2 O}∞ , CP5 {[Mn2 (µ-dpa)2 (µ-4,4'-bpe)2 ]⋅1/2 DEF}∞ , and CP6 {[Mn(µ-dpa)(µ-4,4'-bpe)1.5 ]⋅1/2 DMA}∞ (dpa=3,5-dicarboxyphenyl azide, 2,2'-bp=2,2'-bipyridine, 1,10-phen=1,10-phenanthroline, 4,4'-bpe=1,2-bis(4-pyridyl)ethylene, 4,4'-bp=4,4'-bipyridine, DEF=N,N-diethylformamide, DMA=N,N-dimethylacetamide), to develop multifunctional CPs. Various techniques, such as single-crystal X-ray diffraction (SXRD), FTIR spectroscopy, elemental analysis, and thermogravimetric analysis, were employed to fully characterize these CPs. The majority of the CPs displayed a four-connected sql topology, whereas CP4 and CP6 exhibited a two-dimensional SnS network architecture, which was further entangled in a polycatenation mode. Compound CP1 displayed an open framework structure. The CPs were scaled down to the nanoregime in a ball mill for cell imaging studies. Whereas CP2 and CP4 were employed for cell imaging with RAW264.7 cells, CP1 was exploited for both cell imaging and heterogeneous catalysis in a cyanosilylation reaction.

Metallogels from Coordination Complexes, Organometallic, and Coordination Polymers.

A supramolecular gel results from the immobilization of solvent molecules on a 3D network of gelator molecules stabilized by various supramolecular interactions that include hydrogen bonding, π-π stacking, van der Waals interactions, and halogen bonding. In a metallogel, a metal is a part of the gel network as a coordinated metal ion (in a discrete coordination complex), as a cross-linking metal node with a multitopic ligand (in coordination polymer), and as metal nanoparticles adhered to the gel network. Although the field is relatively new, research into metallogels has experienced a considerable upsurge owing to its fundamental importance in supramolecular chemistry and various potential applications. This focus review aims to provide an insight into the development of designing metallogelators. Because of the limited scope, discussions are confined to examples pertaining to metallogelators derived from discrete coordination complexes, organometallic gelators, and coordination polymers. This review is expected to enlighten readers on the current development of designing metallogelators of the abovementioned class of molecules.