4-position Of Pyridine Research Articles

Gadolinium-based contrast agents built of DO3A-pyridine scaffold: Precisely tuning carboxylate group for enhanced magnetic resonance imaging

It is greatly desired to develop novel gadolinium-based contrast agents (GBCAs) as improved platforms for magnetic resonance imaging (MRI). Herein, we report the syntheses of a series of nonionic cyclen-based GBCAs by precisely tuning carboxylate group on DO3A-pyridine scaffold. [Gd-DO3A-4cp] is isolated which adopts an octadentate coordination mode with a free carboxylate group at 4-position of pyridine. It shows the r1 relaxivity of 5.8 (mmol/L)−1 s-1 (3 T, 25 °C), which is 75% higher than 3.3 (mmol/L)−1 s-1 of the clinic used [Gd-DOTA]. The possible mechanisms behind the enhanced relaxivity are investigated and proposed by structure-property relationship studies. After validation of low cytotoxicity and considerable kinetic inertness, in-vivo studies are further examined, demonstrating its good MRI performance, biodistribution as well as the way of excretion.

Synthesis of 12-Membered Tetra-aza Macrocyclic Pyridinophanes Bearing Electron-Withdrawing Groups.

The number of substituted pyridine pyridinophanes found in the literature is limited due to challenges associated with 12-membered macrocycle and modified pyridine synthesis. Most notably, the electrophilic character at the 4-position of pyridine in pyridinophanes presents a unique challenge for introducing electrophilic chemical groups. Likewise, of the few reported, most substituted pyridine pyridinophanes in the literature are limited to electron-donating functionalities. Herein, new synthetic strategies for four new macrocycles bearing the electron-withdrawing groups CN, Cl, NO2, and CF3 are introduced. Potentiometric titrations were used to determine the protonation constants of the new pyridinophanes. Further, the influence of such modifications on the chemical behavior is predicted by comparing the potentiometric results to previously reported systems. X-ray diffraction analysis of the 4-Cl substituted species and its Cu(II) complex are also described to demonstrate the metal binding nature of these ligands. DFT analysis is used to support the experimental findings through energy calculations and ESP maps. These new molecules serve as a foundation to access a range of new pyridinophane small molecules and applications in future work.

Synthesis of 2,4,6-Trisubstituted Pyridines by Oxidative Eosin Y Photoredox Catalysis.

Eosin Y, an organic dye, was activated as a photoredox catalyst in the presence of molecular oxygen using visible light and, when it was used in the reaction of aryl ketones and benzyl amines, afforded good yields (52-87%) of 2,4,6-triarylpyridines (21 examples) at ambient temperature. The aryl groups at the 2- and 6-positions are derived from ketones, while benzyl amine plays the dual role of providing an aryl functionality at the 4-position of pyridine as well as being a nitrogen donor.

Design and synthesis of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines as novel and selective topoisomerase II-targeted antiproliferative agents

To develop novel selective topoisomerase II inhibitors, we designed and synthesized a series of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines and evaluated their topoisomerase inhibitory activity and cytotoxicity against three human cancer cell lines (DU145, HCT15, and T47D) and a normal cell line (MCF10A). All of the prepared compounds displayed stronger or similar topoisomerase II inhibitory activity as well as cytotoxicity against three human cancer cell lines compared to etoposide. Compounds 10a, 10g, 11a, 11f, 11g, 12a, 12f, and 12g especially showed stronger topoisomerase II inhibitory activity as compared to etoposide at both 100μM and 20μM. A structure–activity relationship study revealed that hydroxyphenyl moiety at 4-position of pyridine and ortho-hydroxyphenyl or thienyl moiety at 2-position of pyridine has an important role in displaying selective topoisomerase II inhibition. The compound 12b with para-hydroxyphenyl and meta-hydroxyphenyl at 4- and 2-position of pyridine, respectively, showed the most significant cytotoxicity against all three cancer cell lines, whereas less cytotoxicity to a normal cell line as compared to adriamycin.

Bistridentate Ruthenium(II)polypyridyl-Type Complexes with Microsecond3MLCT State Lifetimes: Sensitizers for Rod-Like Molecular Arrays

A series of bistridentate ruthenium(II) polypyridyl-type complexes based on the novel 2,6-di(quinolin-8-yl)pyridine (dqp) ligand have been synthesized and their photophysical properties have been studied. The complexes are amenable to substitution in the 4-position of the central pyridine with conserved quasi-C2v symmetry, which allows for extension to isomer-free, rod-like molecular arrays for vectorial control of electron and energy transfer. DFT calculations performed on the parent [Ru(dqp) 2](2+) complex (1) predicted a more octahedral structure than in the typical bistridentate complex [Ru(tpy)2](2+) (tpy is 2,2':6',2"-terpyridine) thanks to the larger ligand bite angle, which was confirmed by X-ray crystallography. A strong visible absorption band, with a maximum at 491 nm was assigned to a metal-to-ligand charge transfer (MLCT) transition, based on time-dependent DFT calculations. 1 shows room temperature emission (Phi = 0.02) from its lowest excited ((3)MLCT) state that has a very long lifetime (tau = 3 micros). The long lifetime is due to a stronger ligand field, because of the more octahedral structure, which makes the often dominant activated decay via short-lived metal-centered states insignificant also at elevated temperatures. A series of complexes based on dqp with electron donating and/or accepting substituents in the 4-position of the pyridine was prepared and the properties were compared to those of 1. An unprecedented (3)MLCT state lifetime of 5.5 micros was demonstrated for the homoleptic complex based on dqpCO2Et. The favorable photosensitizer properties of 1, such as a high extinction coefficient, high excited-state energy and long lifetime, and tunable redox potentials, are maintained upon substitution. In addition, the parent complex 1 is shown to be remarkably photostable and displays a high reactivity in light-induced electron and energy transfer reactions with typical energy and electron acceptors and donors: methylviologen, tetrathiofulvalene, and 9,10-diphenylanthracene. This new class of complexes constitutes a promising starting point for the construction of linear, rod-like molecular arrays for photosensitized reactions and applications in artificial photosynthesis and molecular electronics.

Synthesis of Eu(III) and Tb(III) complexes with novel pyridine dicarboxylic acid derivatives and their fluorescence properties

Starting from pyridine-2,6-dicarboxylic acid (DPA), a series of novel pyridine-2,6-dicarboxylic acid derivatives were synthesized. In these compounds, 4-(hydroxymethyl)pyridine-2,6-dicarboxylate (4-HMDPA) and 4-[(bis-carboxymethyl-amino)-methyl]-pyridine-2,6-dicarboxylic acid (4-BMDPA) were used as multifunctional ligands to coordinate with Tb(III) and Eu(III) and the complexes were prepared. The fluorescence properties of the solid complexes and their solutions were investigated in detail. The results indicated that the weak election-withdrawing group 4-hydroxymethyl in 4-position of pyridine in 4-HMDPA could weaken the fluorescence intensity of the lanthanide complexes. The contradistinctive experimental results showed that the fluorescence intensities of these complexes are related to pH values of the aqueous solutions and the dipole moments of solvent molecules: in the neutral aqueous solutions, the fluorescence intensities of these complexes were strongest, while the dipole moments were lower when the fluorescence intensities were stronger. 4-BMDPA is the better sensitizer and may be used as time-resolved fluoroimmunoassay.

Electrophilic aromatic reactivities via pyrolysis of esters. Part 21. σ+Values for thiazole: the high polarisability of thiazole, and the effect of hydrogen bonding on the reactivity of N-containing heterocycles

The rates of gas-phase elimination of acetic acid from 1-arylethyl acetates (aryl = thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, or phenyl) have been measured between 633.2 and 698.5 K. The relative rates of pyrolysis at 650 K are: thiazol-2-yl, 0.271; thiazol-4-yl, 0.491; and thiazol-5-yl, 1.104; coupled with the previously determined ρ factor for the reaction (–0.61 at 650 K), this leads to the corresponding σ+ values 0.93, 0.505, and –0.07. The positional reactivity order, and the reactivity relative to benzene, are correctly predicted by π-electron density calcuations. The reactivity of each position is substantially less than in solvolysis of the corresponding 1-aryl-1-chloroethanes, in contrast to the reactivity of thiophene which is closely similar in both pyrolysis and solvolysis reactions. Thiazole is thus much more polarisable than thiophene, and hence particularly susceptible to demands for resonance stabilisation of the respective transition states, the demand being less in the pyrolysis. The difference between the reactivities of the 2-position of thiazole and the corresponding α-position of thiophene (1.72 sigma units) is substantially greater than the difference between the reactivities of the 4-position of thiazole and the β-position of thiophene (0.885 sigma units). This reflects the high 2,3-vs. 3,4-bond orders, and consequent variation in the deactivation by the (ortho) nitrogen atom. Nitrogen deactivates the 4-position more than it deactivates the 5-position, as expected. By contrast, in solvolysis the 5-position is deactivated more than the 4-position. This latter anomaly is attributed to hydrogen bonding, which is attenuated when the probe group is adjacent to the ring nitrogen atom. This explanation also accounts for the anomalously low reactivity of the 3- and 4-position of pyridine in determination of the electrophilic reactivity via solvolysis, as compared with gas-phase data, whereas the reactivity of the 2-position is the same in both reactions.

A Mössbauer spectroscopic study of the electronic states of tetragonal iron(II) pyridine complexes

The Mössbauer spectra of FeL 4Cl 2 (L = pyridine, 4-methylpyridine, 3-acetylpyridine) and Fe L 2Cl 2 (L = pyridine, 4-acetylpyridine, 4-chloropyridine, 3-chloropyridine) were measured between 4·2 and 290°K. The magnitudes of the quadrupole splittings ( ΔE Q ) of FeL 4Cl 2 are much larger than those of FeL 2Cl 2, probably because of the different orbital ground-states: d xy for FeL 4Cl 2 and, most likely, d xz and d yz for FeL 2Cl 2. The energy separation, δt 2 g , was estimated from the temperature dependence of ΔE Q . No effect on the isomer shift of a substituent at the 3- or 4-position of pyridine is observed in either FeL 4Cl 2 or FeL 2Cl 2.

The basicities of some organosilicon-, organogermanium- and organotin-substituted pyridines

The p K a values have been measured of some organosilicon-, -germanium-, or -tin-substituted pyridines. For the compounds studied the Me 3M group (M=Si, Ge, or Sn) in the 2-, 3-, or 4-position of pyridine is electron donating which is contrary to the observed effects of these groups when p-substituted in benzoic acids. The 2-substituted pyridines show exalted p K a values due to the formation of a complex with the solvent.

Ultraviolet Absorption Spectra of Three Isomeric Pyridinemethanols and Their N-Oxides

Abstract The ultraviolet absorption spectra of three isomeric pyridinemethanols and their N-oxides were measured in various solvents, n–π* Absorption was observed as the shoulder absorption only in n-hexane solution of 3-pyridinemethanol, for which a qualitative discussion was made. It was also found that the substituiton of a hydroxymethyl group in 4-position of pyridine or 2-position of pyridine N-oxide caused the blue shift. To explain this fact the presence of a weak intramolecular hydrogen bond in 2-pyridinemethanol N-oxide was assumed.