Proton Chemical Shifts Research Articles

Quantum chemical calculations and molecular docking studies of 5-amino-3-(2,5-dimethoxyphenyl)-1-isonicotinoyl-2,3-dihydro-1H-pyrazole-4-carbonitrile

Abstract The five-membered heterocycle pyrazole has two nitrogen atoms next to each other. Natural items and pharmaceuticals using pyrazole as the nucleus have demonstrated a wide range of biological activity. Medications with pyrazole cores may have better pharmacokinetics and pharmacological effects than medicines with similar heterocyclic rings. This is because the pyrazole core has unique physicochemical properties. In this study, 5-amino-3-(2,5-dimethoxyphenyl)-1-isonicotinoyl-2,3-dihydro-1H-pyrazole-4-carbonitrile is synthesized and characterized by means of spectrum and quantum chemical techniques. Using UV–vis absorption technique, Fourier transform infrared (FT-IR), and Fourier transform Raman (FT-Raman) techniques, the spectroscopic properties were examined. There were two regions visible in the experimental Raman as well as infrared spectra: 4,000–400 cm−1 along with 4,000–100 cm−1. The ideal molecular shape, vibrational frequencies, infrared intensity levels, and scattering from Raman were all assessed using density functional theory. The 13C (carbon) and 1H (proton) chemical shifts of the molecule were determined using nuclear magnetic resonance (NMR). The TD-DFT scheme was utilized to figure out speculative ultraviolet values and compare them to oscillator strength, electron excitation energies, and spectrum data from experiments. It is evident from the predicted HOMO-LUMO band separation energies that the transmission of charge takes place within a molecule’s structure. The chemical reactivity of the molecule has been calculated along with other global descriptive properties. Scientists investigated how charges move and the density of electrons inside a molecule using NBO analysis of the chemical they were studying. After examining the molecular electrostatic potential (MEP), a 3D picture was created that shows the compound’s nucleophilic and electrophilic areas. In addition to meeting all pertinent pharmacokinetic requirements, 5-amino-3-(2,5-dimethoxyphenyl)-1-isonicotinoyl-2,3-dihydro-1H-pyrazole-4-carbonitrile is also readily absorbed by the gastrointestinal system. Additionally, the chemical that was synthesized had a positive interaction with the target proteins of treatments for viruses, asthma, and heart failure, as shown by molecular docking.

Studies on the Termination Behavior of Styrenic Free‐Radicals

AbstractIn order to provide more evidence to understand the termination mechanism in styrene free‐radical polymerization, (1‐bromoethyl) benzene and polystyrene with bromide end group (PSt‐Br) synthesized by atom transfer radical polymerization (ATRP) were used as the model compound and model polymer to study the termination behavior of styrenic radical by atom transfer radical coupling (ATRC), and then the NMR chemical shifts of the head‐to‐head enchainment from coupling termination were obtained. SEC and different NMR measurement methods were used to analyze and characterize the products. It is confirmed that there is no bimolecular disproportionation termination between styrenic free radicals, but only coupling termination to form the head‐to‐head enchainment. The proton and carbon chemical shifts of the head‐to‐head enchainment from coupling termination for (1‐bromoethyl) benzene are 2.7–2.86 ppm and ~47.3 ppm. As for the polystyrene through ATRC from PSt‐Br, the corresponding chemical shifts are 2.61–3.29 ppm and ~46.4 ppm, respectively, they are almost the same as the data in our previous paper (~3.05 ppm, ~46.6 ppm) for polystyrene initiated by BPO, proving that the chain termination in free‐radical polymerization of styrene initiated by BPO occurs through primary termination between chain radical and primary radical rather than bimolecular termination between chain radicals.

The conformational properties of alamethicin in ethanol studied by NMR.

Alamethicin, a peptide consisted of 20 amino acid residues, has been known to function as an antibiotic. The peptides self-associate in biological membranes, form an ion channel, and then induce cell death by leaking intracellular contents through a transmembrane pore of an ion channel. We investigated conformation and its thermal stability of alamethicin-A6 and -U6 in ethanol using proton nuclear magnetic resonance (NMR) spectroscopy; alamethicin-A6 and -U6 have the amino acid sequences of UPUAUAQUVUGLUPVUUQQO and UPUAUUQUVUGLUPVUUQQO, respectively, where U and O represent α-aminoisobutyric acid and phenylalaninol, respectively. As indicated by the under bars in the sequences, only the residue 6 differs between the alamethicins. We show that the alamethicins in ethanol form helix conformation in the region of the residues 2-11 and a non-regular conformation in the regions of the N- and C-termini, and that the helices are maintained up to 66°C at least. Conformations in the region of the residues 12-18 of the alamethicins, however, are not well identified due to the lack of NMR data. In addition, we demonstrate that the amide proton chemical shift temperature coefficients' method, which is known as an indicator for intramolecular hydrogen bonds in peptides and proteins in aqueous solutions, can be also applied to the alamethicins in ethanol. Further, we show that the conformation around the C-terminus of alamethicin-A6 is restrained by intramolecular hydrogen bonds, whereas that of alamethicin-U6 is either restrained or unrestrained by intramolecular hydrogen bonds; the alamethicin-U6 molecules having the restrained and unrestrained conformations coexist in ethanol. We discuss the two types of conformations using a model chain consisting of particles linked by rigid bonds called as the free jointed chain.

Java Script Programs for Calculation of Dihedral Angles with Manifold Equations

Java Script programs for calculation dihedral angles from NMR data with manifold equations of 3-Sphere approach: rectangle, Villarceau circles of cyclide (Torus – Dupin Cyclide), polar equations, Euler-Conic. Manifolds are curves or surface in higher dimension used for calculation of dihedral angles under wave character of NMR data, carbon and/or proton chemical shift δ<sub>Xn</sub>[ppm] and vicinal coupling constant <sup>3</sup><I>J</I><sub>HnHn+1</sub>[Hz]. 3-Sphere approach for calculation of the dihedral angles from NMR data in four steps: 1. Prediction, or more exactly calculation of the dihedral angles from vicinal coupling constant with trigonometric equations, 2. Calculation of the dihedral angles from manifold equations; 3. Building units from angle calculated with one of the manifold equations; 4. Calculation the vicinal coupling constant of the manifold dihedral angle. In this paper are presented Java Script programs of step 2 and from step 3 only the Java Script program for calculation of seven sets angles. The bond distances l<sub>CnCn+1</sub>[A<sup>0</sup>] between two atoms of carbon are under different polar equations (<i>i.e.</i> limaçons or cardioid, rose or lemniscale), our expectation was to find different manifold equations for calculation the best angle, differences are smaller but can be find sometimes a preferred one for a vicinal coupling constant. 3-Sphere approach has the advantages of calculation from vicinal angle or/and chemical shift the dihedral angle, tetrahedral angle and the bond distance l<sub>CnCn+1</sub>[A<sup>0</sup>], with application on conformational and configurational analysis.

Persimmon leaf polyphenols as potential ingredients for modulating starch digestibility: Effect of starch-polyphenol interaction

The interaction mode between persimmon leaf polyphenols (PLP) and corn starch with different amylose content and its effect on starch digestibility was studied. Results of iodine binding test, TGA, and DSC revealed that PLP interacted with starch and reduced the iodine binding capacity and thermal stability of starch. High amylopectin corn starch (HAPS) interacted with PLP mainly via hydrogen bonds, since the FT-IR of HAPS-PLP complex showed higher intensity at 3400 cm−1 and an obvious shift of 21 cm−1 to shorter wavelength, and the chemical shifts of protons in 1H NMR and the shift of C-6 peak in 13C NMR of HAPS moved to low field with the addition of PLP. Results of 1H NMR also showed the preferential formation of hydrogen bonds between PLP and OH-3 of HAPS. Different from HAPS, PLP formed V-type inclusion complex with high amylose corn starch (HAS) because XRD of HAS-PLP complex showed characteristic feature peaks of V-type inclusion complex and C-1 signal in 13C NMR of PLP-complexed HAS shifted to low field. Interaction with PLP reduced starch digestibility and HAS-PLP complex resulted in more resistant starch production than HAPS-PLP complex. To complex PLP with starch might be a potential way to prepare functional starch with slower digestion.

Do Electrostatics Control the Diffusive Dynamics of Solitary Water? NMR and MD Studies of Water Translation and Rotation in Dipolar and Ionic Solvents.

NMR-based measurements of the diffusion coefficients and rotation times of solitary water and benzene at 300 K are reported in a diverse collection of 13 conventional organic solvents and 10 imidazolium ionic liquids. Proton chemical shifts of water are found to be correlated to water OH-stretching frequencies, confirming the importance of electrostatic interactions in these shifts. However, the influence of magnetic interactions in aromatic solvents renders chemical shifts a less reliable indicator of electrostatics. Diffusion coefficients (DB) and rotational correlation times (τB) of benzene in the solvents examined are accurately described as functions of viscosity (η) by DB ∝ η-0.81 and τB ∝ η0.64. Literature values of DB and τB in alkane and normal alcohols, which were not included among the solvents studied here, are systematically faster than predicted by these correlations, indicating that factors beyond solvent viscosity play a role in determining the friction on benzene. In contrast to benzene, water diffusion and rotation are poorly described in terms of viscosity alone, even in the dipolar and ionic solvents measured here. The present data and the substantial literature data already available on dilute water diffusion show a systematic dependence of DW on solvent polarity among isoviscous solvents. The aspect of solvent polarity most relevant to water dynamics is the ability of a solvent to accept hydrogen bonds from water, as conveniently quantified by the frequency of water's OH stretching band, ΔνOH. The friction on translation, ζtr = kBT/DW, and rotation, ζrot = kBTτW, are both well correlated by functions of the form ζ(η, ΔνOH) = a1ηa2 exp (a3ΔνOH), where the ai are adjustable parameters. Molecular dynamics simulations reveal a strong coupling between electrostatic and nonelectrostatic water-solvent interactions, which makes it impossible to dissect the friction on water into additive dielectric and hydrodynamic components. Simulations also provide a tentative explanation for the unusual form of the correlating function ζ(η, ΔνOH), at least in the case of ζrot.

N‐Pyridylureas as Masked Isocyanates Fort the Late‐Stage Diversification of Pyridine‐N‐Oxides

AbstractA new method for the synthesis of pyridine‐ and quinoline‐N‐oxides containing a ureido or carbamoyl fragment in position 2 has been developed. This method concluded in the oxidation of relatively readily available substituted N,N‐dimethyl‐N′‐(pyridine‐2‐yl)ureas to the corresponding N‐oxides, followed by modification of the dimethylureide moiety. Being heated to 90 °C in the presence of amines in a solution of DMF or chlorobenzene, N‐oxide of N,N‐dimethyl‐N′‐(pyridine‐2‐yl)urea undergoes a transamination reaction without loss of the N‐oxide function. This produces N‐oxides of N‐alkyl/aryl‐N’‐(pyridine‐2‐yl)ureas in 24–99 % yields, (about 30 examples). Values of the NH protons chemical shifts are a good criterion for the selectivity of the reaction. The reaction is also applicable to N‐oxides of ureas substituted in the pyridine ring and to the quinoline congener. N‐Oxides of pyridine/quinoline‐containing carbamates can be similarly prepared by heating N‐oxides of N,N‐dimethyl‐N′‐(pyridine‐2‐yl)/(quinoline‐2‐yl)‐urea in an appropriate alcohol solution at 120 °C.

Chiral recognition and discrimination studies of tyrosine enantiomers on (-)-18-crown-6-tetracarboxylic acid as a chiral selector by nuclear magnetic resonance spectroscopy and docking simulations.

Considering the substantial significance of chiral biomolecules, such as amino acids, in our daily routines, we performed chiral recognition and discrimination of tyrosine (Tyr) enantiomers on (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid [(-)-18-C-6-TA] as crown-ether type chiral selector (CS) by nuclear magnetic resonance (NMR) spectroscopy and docking simulations. In this study, successful discrimination of the enantiomers of Tyr was achieved, as evidenced by the proton chemical shift differences (ΔΔδ) of Tyr enantiomers observed in the 1 H NMR spectra with (-)-18-C-6-TA CS. We compared the results of these two techniques with the findings obtained from high performance liquid chromatography (HPLC) investigations. In both NMR and HPLC experimental and docking simulation studies, a stronger interaction between the L-Tyr enantiomer with (-)-18-C-6-TA CS than the D-Tyr was consistently observed. Also, the binding energy differences (ΔΔEL-D ) found in simulation data that correspond to enantioselectivity aligned well with the NMR experimental result.

Crystal structure validation of verinurad via proton-detected ultra-fast MAS NMR and machine learning.

The recent development of ultra-fast magic-angle spinning (MAS) (>100 kHz) provides new opportunities for structural characterization in solids. Here, we use NMR crystallography to validate the structure of verinurad, a microcrystalline active pharmaceutical ingredient. To do this, we take advantage of 1H resolution improvement at ultra-fast MAS and use solely 1H-detected experiments and machine learning methods to assign all the experimental proton and carbon chemical shifts. This framework provides a new tool for elucidating chemical information from crystalline samples with limited sample volume and yields remarkably faster acquisition times compared to 13C-detected experiments, without the need to employ dynamic nuclear polarization.

Two Teams Are Better Than One: Where Theory and Experiment Successfully Interact

AbstractThis invited Team Profile was created by Prof. Judy I. Wu, Department of Chemistry, University of Houston (USA) and Prof. Michael M. Haley, Department of Chemistry & Biochemistry and the Materials Science Institute, University of Oregon, Eugene (USA). The X‐ray structure of tetra‐t‐butyl‐s‐indacene was reported in 1986 to possess a symmetric, delocalized D2h geometry, which went against conventional wisdom that this antiaromatic should exhibit a bond‐localized C2h structure. Computational studies over the ensuing 35+ years yielded conflicting outcomes as to the preferred geometry. A computational reexamination of this structure by our team found experimental proton chemical shifts matched best with a computed C2h symmetry, confirming a bond‐localized geometry. “Tetra‐tert‐butyl‐s‐indacene is a Bond‐Localized C2h Structure and a Challenge for Computational Chemistry”, L. J. Karas, S. Jalife, R. V. Viesser, J. V. Soares, M. M. Haley, J. I. Wu, Angew. Chem. Int. Ed. 2023, 62, e202307379.

Two Teams Are Better Than One: Where Theory and Experiment Successfully Interact.

This invited Team Profile was created by Prof. Judy I. Wu, Department of Chemistry, University of Houston (USA) and Prof. Michael M. Haley, Department of Chemistry & Biochemistry and the Materials Science Institute, University of Oregon, Eugene (USA). The X-ray structure of tetra-t-butyl-s-indacene was reported in 1986 to possess a symmetric, delocalized D2h geometry, which went against conventional wisdom that this antiaromatic should exhibit a bond-localized C2h structure. Computational studies over the ensuing 35+ years yielded conflicting outcomes as to the preferred geometry. A computational reexamination of this structure by our team found experimental proton chemical shifts matched best with a computed C2h symmetry, confirming a bond-localized geometry. "Tetra-tert-butyl-s-indacene is a Bond-Localized C2h Structure and a Challenge for Computational Chemistry", L. J. Karas, S. Jalife, R. V. Viesser, J. V. Soares, M. M. Haley, J. I. Wu, Angew. Chem. Int. Ed. 2023, 62, e202307379.

Experimental and theoretical comparison of the vibrational and NMR spectra of novel 6-6’-(1E-1’E)-(Propane-1,3Diylbis (Azanylyidene)) Bis (Phenylmethylylidene)) Bis (3-Octyloxy) Phenol), NBO and molecular docking studies

The characterization study of the synthesized novel compound 6-6’-(1E-1’E)-(Propane-1,3Diylbis(Azanylyidene))Bis(Phenylmethylylidene))Bis(3-Octyloxy)Phenol) (C45H58N2O4) was done by FT-IR, Raman and NMR spectra. Vibrational analysis was realized with normal coordinate treatment, and vibrational modes were assigned in the mid-IR region. The 13C and 1H -NMR spectra of the title compound were measured in DMSO and chloroform, and the corresponding chemical shifts were calculated in the different basis sets (6-31++G(d,p), 6-311G(2d,p), 6-311++G(2d,p), TZVPP) of DFT-B3LYP with continuum models. The vibrational and NMR spectroscopies show that the existence of the intramolecular resonance-assisted hydrogen bonds(O-H...N) results in the redshift of OH vibrational modes and its high proton chemical shifts (ca. 16 ppm), as confirmed by X-ray crystal structure and NRT studies.13C NMR chemical shifts of the Schiff base bond are determined as ca. 174 ppm. The calculations indicate that both the intramolecular hydrogen bond strength and the OH-proton chemical shift increase with increasing solvent polarity. The molecular docking studies reveal that the title ligand has the potency of inhibition against the VIM-2 and NDM-1 active sites of metallo-β-lactamase receptor.

Modeling, spectroscopic structural properties of platinum-II complexes of 2-((phenylimino)methyl)phenolate-based ligands and research of nonlinear optical, organic light emitting diode and solar cell performances

The hypothetical Pt(B1)2, Pt(B2)2 and Pt(B3)2 complexes were modeled. B1, B2 and B3 are Schiff bases, 2-((phenylimino)methyl)phenolate, 4-methyl-2-((phenylimino)methyl)phenolate and 4-nitro-2-((phenylimino)methyl)phenolate, respectively. The ground state structures of the complexes were computed at the DFT-B3LYP/6–31 G(d)/LANL2DZ level. From the characteristic bond lengths, bond angles, bond stretching frequencies and proton chemical shift values, the platinum environment geometry was found to be square plane. The nonlinear optical (NLO) activities of the complexes were investigated by calculating some nonlinear optical property parameters and NLO performance of Pt(B3)2 was found to be higher than other complexes. Organic light emitting diode (OLED) performances of the complexes were investigated and found that the all complexes could be suitable for the production of OLED-featured materials. The solar cell (SC) performances of the complexes were determined by considering the power conversion efficiency (PCE). it was suggested that the Pt(B3)2 complex might have the highest solar cell performance.

On the Efficiency of the Density Functional Theory (DFT)-Based Computational Protocol for 1H and 13C Nuclear Magnetic Resonance (NMR) Chemical Shifts of Natural Products: Studying the Accuracy of the pecS-n (n = 1, 2) Basis Sets.

The basis set issue has always been one of the most important factors of accuracy in the quantum chemical calculations of NMR chemical shifts. In a previous paper, we developed new pecS-n (n = 1, 2) basis sets purposed for the calculations of the NMR chemical shifts of the nuclei of the most popular NMR-active isotopes of 1-2 row elements and successfully approbated these on the DFT calculations of chemical shifts in a limited series of small molecules. In this paper, we demonstrate the performance of the pecS-n (n = 1, 2) basis sets on the calculations of as much as 713 1H and 767 13C chemical shifts of 23 biologically active natural products with complicated stereochemical structures, carried out using the GIAO-DFT(PBE0) approach. We also proposed new alternative contraction schemes for our basis sets characterized by less contraction depth of the p-shell. New contraction coefficients have been optimized with the property-energy consistent (PEC) method. The accuracies of the pecS-n (n = 1, 2) basis sets of both the original and newly contracted forms were assessed on massive benchmark calculations of proton and carbon chemical shifts of a vast variety of natural products. It was found that less contracted pecS-n (n = 1, 2) basis sets provide no noticeable improvement in accuracy. These calculations represent the most austere test of our basis sets as applied to routine calculations of the NMR chemical shifts of real-life compounds.

NMR characterization of proton exchange membranes in controlled hygrometry conditions

NMR methods are highly sensitive to the state of water adsorbed in ionomer membranes for PEM fuel cells and electrolyzers. This study demonstrates the potential of NMR and MRI to reliably and accurately determine a wide range of water parameters such as proton chemical shift, transverse relaxation time, water content, and membrane thickness. Measurements are carried out in-situ in membranes in contact with humid air flows that are precisely controlled in terms of flow rate, temperature, and humidity. This precise management of the climatic conditions makes it possible to detect very small variations in the parameters measured, linked to the hydrothermal history of the membrane described in the literature. This history is erased when the membrane is humidity cycled several times. In addition, we demonstrate the use of this MRI imaging method to determine the resistance to water transfer across the membrane/humid air interface under steady-state conditions. Finally, we propose a refinement of the imaging method that reduces acquisition time by a factor of two, without degrading the 1D water content profile. This improvement gives us access to the study of transient hydration regimes typical of PEMFC and PEME operation.

Tetra‐tert‐butyl‐s‐indacene is a Bond‐Localized C2h Structure and a Challenge for Computational Chemistry

AbstractWhether tetra‐tert‐butyl‐s‐indacene is a symmetric D2h structure or a bond‐alternating C2h structure remains a standing puzzle. Close agreement between experimental and computed proton chemical shifts based on minima structures optimized at the M06‐2X, ωB97X‐D, and M11 levels confirm a bond‐localized C2h symmetry, which is consistent with the expected strong antiaromaticity of TtB‐s‐indacene.

Synthesis of Novel Polymers via ROMP of Benzyne‐Derived Monomers and Their NMR Spectroscopic Properties

AbstractDehydrohalogenation of 1,4‐dihalobenzenes and 1,2,4‐trichlorobenzene is performed using n‐BuLi to form benzynes. These benzynes are used as dienophiles in a Diels–Alder reaction with the dienes furan and 2,5‐dimethylfuran to prepare new benzonorbornadiene derivatives. The cycloadducts of furan are polymerized by a ring‐opening metathesis reaction using a Hoveyda–Grubbs ruthenium catalyst. The polymers are characterized by 1H NMR (nuclear magnetic resonance), and unambiguous proton chemical shift assignments are based on the multiplicity pattern of proton resonances. This is confirmed by 2D NMR data from HSQC(Heteronuclear Single Quantum Coherence) and COSY (Correlation Spectroscopy) spectra. The polybenzonorbornadienes have both cis and trans conformation in their chemical structure. The trans conformation is qualitatively in greater proportion observed at 1H NMR experiments. These materials may have syndiotactic microstructure by the lack of correlations in COSY.

RETRACTED: Mechanistic insight into the bioactivity of prodigiosin-entrapped lipid nanoparticles against triple-negative breast, lung and colon cancer cell lines

This research investigates the potentials of prodigiosin(PG) derived from bacteria and its formulations against triple-negative breast (TNB), lung, and colon cancer cells. The PG was extracted from S. marcescens using continuous batch culture, characterized, and formulated into lyophilized parenteral nanoparticles (PNPs). The formulations were characterized with respect to entrapment efficiency (EE), DSC, FT-IR, TEM, and proton nuclear magnetic resonance (1H NMR) spectroscopy. In vitro drug release was evaluated in phosphate buffer (pH 7.4) while acute toxicity, hematological and histopathological studies were performed on rats. The in vitro cytotoxicity was evaluated against TNB (MCF-7), lung (A-549), and colon (HT-29) cancer cell lines. High EE (92.3±12%) and drug release of up to 89.4% within 8h were obtained. DSC thermograms of PG and PG-PNPs showed endothermic peaks indicating amorphous nature. The FT-IR spectrum of PG-PNPs revealed remarkable peaks of pure PG, indicating no strong chemical interaction between the drug and excipients. The TEM micrograph of the PG-PNPs showed nano-sized formulations (20-30nm) whose particles were mostly lamellar and hexagonal structures. The 1H NMR result revealed the chemical structure of PG showing all assigned proton chemical shifts. Toxicity results of the PG and its formulation up to a concentration of 5000mg/kg showed insignificant vacuolar changes of hepatocytes in the liver, with normal renal medulla and cortex in the kidney. The PG and PG-PNPs inhibited the growth of breast, lung, and colon cell lines. The nano-sized lipid formulation (PG-PNPs) showed potential in PG delivery and cancer treatments.

Synthesis, molecular structure, spectral characterization, and biological activities of ethyl 2-(4-(4-chlorobenzyl)-3-methyl-6-oxopyridazin-1(6H)-yl)acetate

The structure of the ethyl 2-(4-(4-chlorobenzyl)-3-methyl-6-oxopyridazin-1(6H)-yl)acetate (COAP) was revealed using single crystal X-ray diffraction method, was solved and refined using the Bruker SHELXTL Software Package, using the space group P 1 21/n 1, with Z = 4 for the formula unit, C16H17ClN2O3. Its spectroscopic and electronic properties were investigated by spectroscopic methods such as 1H and 13C NMR, FT-IR and UV–vis. The electronic structure properties of the compound were investigated with quantum mechanical calculations. It was observed that crystal packaging is provided by CH…O type hydrogen bonds. Also, spectroscopic properties such as FT-IR vibrational wave numbers, proton and carbon NMR chemical shifts and UV–vis. absorption parameters were calculated. In addition, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) analyses and Molecular Electrostatic Potential (MEP) surface, NBO analysis were computed to understand the reactive regions of the title compound. All computations were performed by using DFT/B3LYP quantum chemical method with 6–311++G(d,p) basis set to compare with the experimental results. The calculations showed that HOMO orbitals localized on π and n orbitals of pyridazine while LUMO orbitals localized on π* orbitals of pyridazine. The major contribution to electronic transitions originated from HOMO LUMO transition calculated at 292.16 nm. Hirshfeld surface analysis was investigated to visualization van der Waals distances, and the space occupied by molecules and to determine the contact regions. The computed geometry parameters and vibrational wavenumbers were in good agreement with the experimental results. Moreover, the potential inhibitory activities of the compound were evaluated on enzymes α-glucosidase. Besides, the compound was tested for it potential in vitro anti-inflammatory activities by Heat induced hemolysis. The results showed that the product had a good percentage of heat induced Hemolysis inhibition.

Acyl Hydrazides and Acyl Hydrazones as High-Performance Chemical Exchange Saturation Transfer MRI Contrast Agents.

Chemical exchange saturation transfer (CEST) MRI is a versatile molecular imaging approach that holds great promise for clinical translation. A number of compounds have been identified as suitable for performing CEST MRI, including paramagnetic CEST (paraCEST) agents and diamagnetic CEST (diaCEST) agents. DiaCEST agents are very attractive because of their excellent biocompatibility and potential for biodegradation, such as glucose, glycogen, glutamate, creatine, nucleic acids, et al. However, the sensitivity of most diaCEST agents is limited because of small chemical shifts (1.0-4.0 ppm) from water. To expand the catalog of diaCEST agents with larger chemical shifts, herein, we have systematically investigated the CEST properties of acyl hydrazides with different substitutions, including aromatic and aliphatic substituents. We have tuned the labile proton chemical shifts from 2.8-5.0 ppm from water while exchange rates varied from ~680 to 2340 s-1 at pH 7.2, which allows strong CEST contrast on scanners down to B0 = 3 T. One acyl hydrazide, adipic acid dihydrazide (ADH), was tested on a mouse model of breast cancer and showed nice contrast in the tumor region. We also prepared a derivative, acyl hydrazone, which showed the furthest shifted labile proton (6.4 ppm from water) and excellent contrast properties. Overall, our study expands the catalog of diaCEST agents and their application in cancer diagnosis.