Effect of the flexible chain length of a dimetal subunit on the formation of 1D coordination polymers to molecular rectangles.

Utilizing the angular and rigid furan dicarboxylate (fdc2-) ion, a new series of four (1-4) metal-organic coordination networks (MOCNs) is synthesized in good yields through a one-pot self-assembly reaction in methanol under ambient conditions to demonstrate the effect of Cu2 dimetal subunits, connected by flexible polypyridyl bis(tridentate) ancillary ligands, tpxn, where x refers to the number of methylene groups connecting the alkyl nitrogen atoms in the ancillary ligands and is equal to 2, 4, 6, and 7. The solid-state molecular structures of 1-4 are determined by single-crystal X-ray diffraction. A change in the dimensionality of the resultant MOCN is observed from a 1D coordination polymer (CP) for 1, 2, and 3 to a molecular rectangle for 4. Furthermore, each unit of 4 contains one NaClO4. Using electrospray ionization (ESI) mass spectrometry, their structural integrity in solution and their purity of existence as a single product are confirmed. Further characterization of 1-4 by FTIR and UV-vis (in solution and solid-state) spectroscopy, and FESEM and TEM is also reported. The presence of unsaturated metal centers in 1-4 provided an opportunity to compare their Lewis acid catalytic activities for the Knoevenagel condensation reaction of malononitrile with various aldehydes.

Design and Synthesis of Lead(II)-Based Electrocatalysts for Oxygen Evolution Reaction.

A well-organized worldwide effort in providing remedies to sustainable clean energy generation and storage has focused on the strategic design and development of stable and efficient earth-abundant metal (Fe, Co, Ni, Pb, etc.)-based electrocatalysts for the oxygen evolution reaction (OER). Unfortunately, examples of Pb-based catalysts for such a process are rare. In this work, based on the dual-linker strategy, we have designed and synthesized two new two-dimensional (2D) coordination polymers of Pb with the hcb topology, [Pb2(tpbn)(adc)2]·4H2O·0.5CH3OH}n (CP1) and {[Pb2(tpbn)(fum)2]·7H2O}n (CP2), in excellent yields by the room-temperature self-assembly of Pb(OAc)2, tpbn, and H2adc or H2fum (where tpbn = N,N',N‴,N‴'-tetrakis-(2-pyridylmethyl)-1,4-diaminobutane, H2adc = acetylene dicarboxylic acid, and H2fum = fumaric acid). In addition to determining their X-ray single crystal structures, the phase purity and thermal stability were established by powder X-ray diffraction and thermogravimetric analysis, respectively. Furthermore, these were also characterized by the microscopic techniques (SEM/EDX and TEM/HRTEM). For their conductive and highly stable nature in alkaline medium, both CP1 and CP2 were tested for their suitability in the OER process. Interestingly, with a subtle change from adc in CP1 to fumarate in CP2 as the dicarboxylate linker, the latter performed much better than the former and displayed an excellent electrochemical stability in basic medium. Remarkably, CP2 has one of the lowest Tafel values (35 mV dec-1) and a low overpotential value (140 mV vs RHE) in 0.5 M KOH compared to those reported for any materials. Such a comparative study with CP1 and CP2, which are the simplest CPs and made with green-chemistry protocols for an easy making in large quantities, provides an outlook to developing the next-generation Pb-based electrocatalysts.

Deciphering supramolecular isomerization in coordination polymers: connected molecular squares vs. fused hexagons.

The self-assembly of Mn(ii), bis(tridentate) ligands and bent dicarboxylate linkers under ambient conditions has been exploited to generate a series of 1D coordination polymers in good yields. For a set of seven compounds, structural isomerization of these architectures is demonstrated through the variation of length and nature of the spacer between the tridentate capping sites of the bis(tridentate) ligands, such as tpbn (N,N',N'',N'''-tetrakis-(2-pyridylmethyl)-1,4-diaminobutane), tphxn (N,N',N'',N'''-tetrakis-(2-pyridylmethyl)-1,6-diaminohexane), and tpxn (N,N',N'',N'''-tetrakis-(2-pyridylmethyl)-xylylamine) or by varying the bent dicarboxylate linker 4,4'-(dimethylsilanediyl)bis-benzoic acid (H2L1) or 4,4'-oxybis-benzoic acid (H2L2). These compounds have been structurally characterized by single-crystal and powder X-ray diffraction, FTIR, and thermogravimetric and elemental analyses. This study reveals that the supramolecular structural variation can be precisely controlled either by a judicious selection of reaction conditions or linker/ligand combinations. For example, the self-assembly of Mn(ii), tpbn and H2L1 in DMF/EtOH/water affords a mixture of products (1 and 1a) while changing the solvent combination to EtOH/water results in the generation of a single isomer (1a) in a highly selective manner. On the other hand, for the Mn(ii)-tphxn system, different structural isomers have been isolated by varying the dicarboxylates, H2L1 and H2L2 (2vs.5). Similarly, for the Mn(ii)-H2L2 system, a variation in the spacer chain length of bis(tridentate) ligands, tpbn and tphxn resulted in the formation of different structural isomers (4vs.5).

Steric Effect of a Capping Ligand on the Formation of Supramolecular Coordination Networks of Ni(II): Solid-State Entrapment of Cyclic Water Dimer.

Supramolecular dimer of water is the simplest of the small water clusters [(H2O) n , n = 2-10]. During the course of our work on supramolecular coordination networks of three-component systems (divalent metal ion, tridentate capping ligand, and ditopic carboxylate linker), a cyclic water dimer is found to be entrapped in the network of [Ni2(6-Mebpta)2(adc)2]·2H2O (1) (6-Mebpta = 2-methyl-N-((6-methylpyridin-2-yl)methyl)-N-(pyridin-2-ylmethyl)propan-2-amine and adc = acetylenedicarboxylate). Based on the single-crystal structure of 1, the water dimer plays an important role in connecting the bis(adc) bridged dinickel synthons to form a one-dimensional (1D) supramolecular network. To emphasize the role of 6-Mebpta in the judicious choice of components for 1, one simple modification to it by having another methyl group in the second pendant pyridyl group to make 6,6'-Me2bpta (2-methyl-N,N-bis((6-methylpyridin-2-yl)methyl)propan-2-amine) did not allow the formation of any water cluster in [Ni(6,6'-Me2bpta)(adc)(H2O)]·H2O (2), where a different coordination environment around Ni(II) is also observed. Further quantification of the difference in supramolecular interactions observed in 1 and 2 has been assessed by Hirshfeld surface analysis. Both 1 and 2 are obtained in good yields at room temperature (methanol as solvent) and are further characterized by elemental analysis, Fourier transform infrared (FTIR) and Raman spectroscopy, powder X-ray diffraction, and thermogravimetric analysis.

Effecting structural diversity in a series of Co(II)-organic frameworks by the interplay between rigidity of a dicarboxylate and flexibility of bis(tridentate) spanning ligands.

In a one-pot self-assembly reaction of Co(OAc)2·4H2O, thiophene-2,5-dicarboxylic acid (H2tdc) and four different bis(tridentate) polypyridyl spanning ligands under ambient conditions, a series of structurally diverse metal-organic frameworks has been synthesised and characterized by single crystal X-ray diffraction: {[Co2(tdc)2(tpbn)(H2O)2]·solvent}n (solvent = 2H2O, 1; solvent = 2CH3OH, 2H2O, 1a), {[Co2(tdc)2(tphn)]·solvent}n (solvent = H2O, 2; solvent = CH3OH, 2.5H2O, 2a), {[Co2(tdc)2(tpchn)(H2O)2]·solvent}n (solvent = 5H2O, 3; solvent = C2H5OH, 2H2O, 3a), and {[Co2(tdc)2(tpxn)]·solvent}n (solvent = 6H2O, 4; when no solvent, 4a), where tpbn (N,N',N'',N'''-tetrakis(2-pyridylmethyl)-1,4-diaminobutane), tphn = N,N',N'',N'''-tetrakis(2-pyridylmethyl)-1,6-diaminohexane, tpchn = N,N'-(cyclohexane-1,4-diylbis(methylene))bis(1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine) and tpxn = N,N'-(1,4-phenylenebis(methylene))bis(1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine). There is a profound effect of the nature of spacer between the alkyl nitrogens in the spanning ligands (flexible vs. semiflexible) on the molecular structures of 1a-4a. The notable differences are (a) the binding mode of the tridentate part of polypyridyl ligands to the Co(ii) center is facial in 1a, 3a and 4a but meridional in 2a, (b) the Co(ii) centers in 1a-3a are hexacoordinated (with a coordinated water in 1a and 3a) but are pentacoordinated in 4a, and (c) the binding mode of tdc linker is bis(monodentate) in 1a, 3a and 4a but chelated in one end and monodentate in the other end in 2a. Thus, the overall framework structure of 1a, 2a, 3a and 4a is cis-decalin type 2D polymer, ladder-shaped 1D polymer, hexagonal 2D net and cis-decalin type 2D polymer, respectively. Their thermal stabilities have been established by thermogravimetric analysis (TGA). The presence of an unsaturated metal center in 4 has provided us an opportunity for its use as an efficient Lewis acid catalyst for the Knoevenagel condensation reaction of malononitrile with various aldehydes (100% conversion in 60 minutes with 2 mol% catalyst in methanol).

A Primary Amide-Functionalized Heterogeneous Catalyst for the Synthesis of Coumarin-3-carboxylic Acids via a Tandem Reaction.

A crystalline primary amide-based bifunctional heterogeneous catalyst, {[Cd2(2-BPXG)(Fum)2(H2O)2]·2H2O}n (1) (where, 2-BPXG = 2,2'-((1,4-phenylenebis(methylene))bis((pyridin-2-ylmethyl)azanediyl)) diacetamide and Fum = fumarate), has been developed for the one-pot synthesis of a series of potentially biologically active coumarin-3-carboxylic acids at room temperature via a Knoevenagel-intramolecular cyclization tandem reaction. Catalyst 1 is prepared at room temperature from a one-pot self-assembly process in 81% yield and high purity within a few hours and has a ladder-like polymeric architecture based on single-crystal X-ray diffraction. Additional characterization of 1 includes elemental analysis, infrared spectroscopy, thermogravimetric analysis, and powder X-ray diffraction. Based on the optimized conditions, it is determined that 1 is highly efficient (conditions: 2 mol % catalyst, 3 h, and 26-28 °C in methanol) for this reaction. Its recyclability up to five cycles without significant loss of activity and structural integrity is also demonstrated. Using both electron-donating and electron-withdrawing substituents on the salicylaldehyde substrate, seven different derivatives of coumarin-3-carboxylic acid were made. Additionally, the monoamine oxidase (MAO) inhibitor, coumarin-3-phenylcarboxamide, has also been synthesized from coumarin-3-carboxylic acid obtained in the catalysis process. A detailed mechanism of action is also provided.

Modulation of hydrophilicity inside the cavity of molecular rectangles self-assembled under ambient conditions.

Three novel molecular rectangles of tetranuclear Cu(ii) with a variation in the flexible methylene chain length on the two opposite sides have been synthesized from a one pot self-assembly reaction in a methanol-water mixture under ambient conditions. Their solid state molecular structures are determined by single crystal X-ray diffractometry, while their structural integrity in the solution state is confirmed by electrospray mass spectrometry. With such a subtle variation, modulation of hydrophilicity inside the cavity of these molecular rectangles is achieved as evident from the water and methanol vapor sorption studies.

Design and Development of a Heterogeneous Catalyst for the Michael Addition of Malononitrile to 2-Enoylpyridines: Influence of the Primary Amide Decorated Framework on Catalytic Activity and Selectivity.

For the Michael addition of malononitrile to 2-enoylpyridines, we report the first heterogeneous catalyst, {[Zn2(2-bpbg)(fum)2]·4H2O·EtOH}n (1) (where 2-bpbg = N,N'-bis(2-pyridylmethyl)-1,4-diaminobutane-N,N'-diacetamide and where fum = fumarate), which is decorated with primary amide side arms. It is prepared from the self-assembly of starting materials in methanol at room temperature (27 °C). Using 3 mol % of 1, greater than 99% conversion of substrates to the desired product is achieved within 1 h at 27 °C. Moreover, the catalyst is recyclable up to five consecutive cycles without significant loss of activity and structural integrity. In order to show the uniqueness of 1, the reaction under the same conditions was catalyzed by a fully pyridyl-based (i.e., having no primary amide group) and isostructural analogue, {[Zn2(tpbn)(fum)2]·6H2O}n (2) (where tpbn = N',N',N″,N''-tetrakis(pyridin-2-ylmethyl)butane-1,4-diamine), but resulting only in 7% conversion. This demonstrates the selective catalytic activity of 1 over 2 due to the presence of the primary amide side arms, where it acts as a bifunctional catalyst through the excellent hydrogen bond donating (HBD) ability in this reaction. For providing an insight into its mechanism of action involving a cyclic seven-membered hydrogen bonding motif, the reaction was performed with freshly synthesized (E)-chalcone, 3-enoylpyridine, and 4-enoylpyridine instead of 2-enoylpyridine under the same conditions. In the case of (E)-chalcone no product formation was observed, whereas for 3-enoylpyridine and 4-enoylpyridine the conversions were only 29% and 25%, respectively. Both 1 and 2 were fully characterized by infrared spectroscopy, elemental analysis, thermogravimetric analysis, and single-crystal and powder X-ray diffraction.

Luminescent Lanthanide-Based Probes for the Detection of Nitroaromatic Compounds in Water.

A new mixed pyridyl-carboxylate ligand with two picolinate chromophores and a flexible linear spacer, potassium 2,2'-(butane-1,4-diylbis((pyridin-2-ylmethyl)azanediyl))diacetate (K2bpbd), which is obtained in high yield and spectroscopically characterized, has been utilized to make new lanthanide complexes, namely, [Ln(bpbd) (H2O)2(NO3)]·xH2O, where Ln = Tb (1) and x = 6, Ln = Sm (2) and x = 7, and Ln = Dy (3) and x = 7. These complexes have been extensively characterized by various spectroscopic techniques (UV-vis and Fourier transform infrared spectroscopy), elemental analyses, thermogravimetric analysis, field emission scanning electron microscopy, and powder X-ray diffraction. These show very intense characteristic luminescence features that confirm the antenna effect of the ligand on the metal center. These complexes have been utilized for the detection of various nitroaromatic compounds. Among these three complexes, 1 is found to be the best for the selective sensing of 2,4,6-trinitrophenol in water with a detection limit of (0.35 ± 0.05) ppm. Its Stern-Volmer constant, K SV [(5.48 ± 0.1) × 104 M-1], is one of the highest among similar sensors reported so far.

Study of a cross-linked hydrogel of Karaya gum and Starch as a controlled drug delivery system.

A cross-linked hydrogel was synthesized using a hybrid backbone of karaya gum starch and grafted with polyacrylic acid. It showed a maximum swelling ratio (SR) of 30.5 g/g at pH 10 and was explored as an oral drug delivery carrier using paracetamol and aspirin as model drugs. In vitro release experiments revealed that maximum drug release at pH 7.4 in comparison to pH 1.2 (simulated intestinal vs gastric fluid) and neutral medium. The release profiles of these drugs showed no initial burst. It also showed good hemocompatibilty and non-cytotoxicity for its employment as a site specific drug delivery agent.

Regeneration, degradation, and toxicity effect of MOFs: Opportunities and challenges.

Metal organic frameworks (MOFs) have been investigated extensively for separation, storage, catalysis, and sensing applications. Nonetheless, problems associated with their toxicity, recycling/reuse/regeneration, and degradation have yet to be addressed as one criterion to satisfy their commercialization. Here, the challenges associated with MOF-based technology have been explored to further expand their practical utility in various applications. We start a brief description of challenges associated with MOF-based technology followed by a critical evaluation of toxicity and need of technical options for regeneration of MOFs. Importantly, diverse techniques/process for reuse and regeneration of MOFs like activation of MOFs by heat, vacuum, solvent exchange, supercritical carbon dioxide (SCCO2) and other miscellaneous options have been discussed with recent examples. Afterward, we also present an economical aspect and future perspectives of MOFs for real world applications. All in all, we aimed to present opportunities and critical review of the current status of MOF technology with respect to their recycling/reuse/regeneration to consider their environmental impact.

Novel primary amide-based cationic metal complexes: green synthesis, crystal structures, Hirshfeld surface analysis and solvent-free cyanosilylation reaction.

A new symmetrical and flexible primary amide functionalized ligand, 2,2'-(ethane-1,2-diylbis((pyridin-2-ylmethyl)azanediyl))diacetamide (2-BPEG), has been synthesized and structurally characterized. Using this multidentate ligand, four novel metal complexes, namely [Cu(2-BPEG)](ClO4)2·0.5H2O (1), [Zn(2-BPEG)](ClO4)2 (2), [Zn(2-BPEG)](ZnCl4)·H2O (3) and [Cd(2-BPEG)(H2O)](ClO4)2·H2O (4), have been synthesized under ambient conditions and characterized by elemental, spectroscopic and thermal analysis, and single and powder X-ray diffraction. Complexes 1-3 are hexacoordinated with an N4O2 donor set (provided by the hexadentate 2-BPEG ligand), while complex 4 is heptacoordinated with an additional coordinated water molecule. In all cases, the 2-BPEG ligand acts as a hexadentate ligand. A change in the starting metal salt has resulted in the formation of 2 and 3 with different tetrahedral anions, ClO4- and ZnCl4-, respectively. This has provided an opportunity to showcase anion-directed supramolecular networks for these compounds. Compounds 1, 2 and 4 with perchlorate anions show similar and comparable intermolecular interactions in their 3D networks. On the other hand, the supramolecular self-assembly of 3 is dominated by a variety of intermolecular interactions such as C-HCl, N-HCl, O-HCl and C-HO due to the presence of a tetrachlorozincate(ii) ion. Moreover, the role of weak intermolecular interactions in the crystal packing has been analysed and quantified using Hirshfeld surface analysis. Furthermore, compound 4 exhibiting an open Lewis acid site has been found to be a very efficient and recyclable heterogeneous catalyst for the solvent-free cyanosilylation of various aldehydes with trimethylsilyl cyanide (TMSCN) producing the corresponding trimethylsilyl ether in high yields.

Correction: An unprecedented tandem synthesis of fluorescent coumarin-fused pyrimidines via copper-catalyzed cross-dehydrogenative C(sp3)-N bond coupling.

Correction for 'An unprecedented tandem synthesis of fluorescent coumarin-fused pyrimidines via copper-catalyzed cross-dehydrogenative C(sp3)-N bond coupling' by Santosh Kumari et al., Org. Biomol. Chem., 2018, 16, 3220-3228.

Alkyl chain-modified cyclometalated iridium complexes as tunable anticancer and imaging agents.

Five mononuclear cyclometalated iridium complexes [1](PF6)-[5](PF6) were prepared using imidazole-based ligands of varying alkyl chain length. The complexes were characterised by various analytical techniques. The single crystal X-ray structures of [2](PF6), [3](PF6) and [4](PF6) revealed the expected distorted Oh structures around the metal centre; however, the chain length was found to play a crucial role in deciding the overall geometry. Theoretical investigations demonstrated that the HOMOs were mainly contributed by iridium and cyclometalated ligands, whereas the LUMOs were constituted from bpy/phen units. The complexes were found to be luminescent with a moderate emission quantum yield and lifetime in CH3CN. The in vitro growth inhibition assay of the complexes with a shorter alkyl chain ([4]+ and [5]+) displayed higher anticancer activity (IC50 < 0.5 µM) compared to the complexes with a longer alkyl chain ([1]+-[3]+) (IC50 < 30 µM) against human breast cancer (MCF-7) cells. The complexes [4]+ and [5]+ also displayed moderate cancer cell selectivity (∼3 times) over normal breast (MCF-10) cells. The flow cytometry assay and fluorescence microscopy analysis suggested that cellular accumulation was primarily responsible for the variation in anticancer activity. Interestingly, without possessing any anticancer activity or toxicity ((IC50 > 50 µM), the complex [1]+ mainly accumulated near the cell membrane outside the cell and displayed a clear image of the cell membrane. The light microscopy images and western blot analysis reveal that complex [4]+ induced combined apoptosis and paraptosis. Thus, tuning the anticancer activity and cellular imaging property mediated by the alkyl chain would be of great importance and would be useful in anticancer research.

An unprecedented tandem synthesis of fluorescent coumarin-fused pyrimidines via copper-catalyzed cross-dehydrogenative C(sp3)-N bond coupling.

An efficient, one-pot Cu-catalyzed tandem synthesis of fluorescent 1-benzyl-2-phenyl-1,2-dihydro-5H-chromeno[4,3-d]pyrimidin-5-ones from 4-chloro-3-formylcoumarin and benzylamines was developed by in situ intramolecular cross-dehydrogenative C(sp3)-N bond formation in moderate-to-good yields under ligand-free ambient conditions. This synthesis was easily scalable, and the generality of the substrates was established. These coumarin-fused pyrimidines exhibited interesting photo-physical properties and high quantum yields, and would be potential candidates for facilitating suitable studies in medicinal chemistry and materials science.

Can Remote N-Heterocyclic Carbenes Coordinate with Main Group Elements? Synthesis, Structure, and Quantum Chemical Analysis of N+ -Centered Complexes.

Remote N-heterocyclic carbenes (rNHCs), such as N-methyl-4-pyridylidene, are known to form coordination complexes with TMs. Herein, it is established that rNHCs can also coordinate to the N+ centre. Synthesis of some novel divalent NI complexes with the general formula (rNHC)→N+ ←(NHC) and (rNHC)→N+ ←(rNHC) was achieved, and X-ray diffraction studies supported the coordination bond character between the rNHCs and the N+ centre. Quantum chemical analysis established the presence of divalent NI character at the central nitrogen in these systems.

Encapsulation of a Water Octamer Chain in a Chiral 2D Sheetlike Supramolecular Coordination Network Composed of Dinickel-Dicarboxylate Subunits.

Four new chiral supramolecular coordination networks of Ni(II) of general formula [Ni2(Hhissal)2(dicarboxylate)(H2O)2]·nH2O (where Hhissal = histidinesalicylate; dicarboxylate = adipate; n = 8 for 1, succinate; n = 4 for 2, maleate; n = 4 for 3, fumarate; and n = 6 for 4) are reported. On the basis of the single-crystal X-ray study, an unprecedented zig-zag chain structure of water octamer encapsulated in 1 has been identified. The supramolecular network of the dimetal subunits is formed through hydrogen bonding interactions between the amine N-H of Hhissal and the oxygen atom of the coordinated water molecule of one subunit with the uncoordinated oxygen atom and the coordinated oxygen atom of the carboxylate group of Hhissal of the next subunit, respectively. The strength of hydrogen bonding within this water cluster (the range of O···O distances is 2.702-2.760 Å) is similar to that found in ice. These networks are further characterized by elemental analysis, IR spectroscopy, powder X-ray diffraction, polarimetry, UV-vis/diffuse reflectance and circular dichroism spectroscopy, and thermogravimetric analysis. A comparison of their properties indicates that these are isostructural with a variation of encapsulated water clusters.

Solvent-Driven Iodine-Mediated Oxidative Strategies for the Synthesis of Bis(imidazo[1,2-a]pyridin-3-yl)sulfanes and Disulfanes.

Two efficient iodine-mediated strategies, which are economical and one-pot, are described to access bis(imidazo[1,2-a]pyridin-3-yl)sulfanes and bis(imidazo[1,2-a]pyridin-3-yl)disulfanes in chloroform and acetic acid, respectively, by a direct oxidative homocoupling of imidazo-heterocycles using inexpensive sodium sulfide as a sulfur source. These strategies are scalable, and an array of substrates delivered their corresponding stable sulfur-bridged imidazo-heterocycles in excellent yields.

Ruthenium(II)-Catalyzed Regioselective Ortho Amidation of Imidazo Heterocycles with Isocyanates.

Direct ortho amidation at the phenyl ring of 2-phenylimidazo heterocycles with aryl isocyanates has been achieved via a chelation-assisted cationic ruthenium(II) complex catalyzed mechanism. The methodology provides a straightforward, high-yielding regioselective approach toward the synthesis of an array of ortho-amidated phenylimidazo heterocycles without prior activation of C(sp2)-H. This also reports the first method for coupling of aryl isocyanates with the imidazo[1,2-a]pyridine system via a pentacyclometalated intermediate. The methodology is found to be easily scalable and could be applied toward the selective ortho amidation of 2-heteroarylimidazo[1,2-a]pyridine frameworks.

Azine-Hydrazone Tautomerism of Guanylhydrazones: Evidence for the Preference Toward the Azine Tautomer.

Guanylhydrazones have been known for a long time and have wide applications in organic synthesis, medicinal chemistry, and material science; however, little attention has been paid toward their electronic and structural properties. Quantum chemical analysis on several therapeutically important guanylhydrazones indicated that all of them prefer the azine tautomeric state (by about 3-12 kcal/mol). A set of simple and conjugated azines were designed using quantum chemical methods, whose tautomeric preference toward the azine tautomer is in the range of 3-8 kcal/mol. Twenty new azines were synthesized and isolated in their neutral state. Variable temperature NMR study suggests existence of the azine tautomer even at higher temperatures with no traces of the hydrazone tautomer. The crystal structures of two representative compounds confirmed that the title compounds prefer to exist in their azine tautomeric form.