Intramolecular Hydrogen Bond Research Articles

Chlorine Substitution Effect on the S1 Relaxation Dynamics of Chlorobenzene and Chlorophenols.

The S1 state relaxation dynamics of chlorobenzene (CB), 3-chlorophenol (3-CP), 3-CP·H2O, and 2-chlorophenol·H2O (2-CP·H2O) have been investigated by means of picosecond time-resolved pump-probe spectroscopy in a state-specific manner. For CB, the S1 state relaxes via the S1-S0 internal conversion in the low internal energy region (<2000 cm-1), whereas the direct C-Cl bond dissociation channel mediated by the upper-lying repulsive πσCCl* state is opened to give the rather sharp increase of the S1 relaxation rate in the high internal energy region (>2000 cm-1). A similar dynamic feature has been observed for 3-CP in terms of the lifetime behavior with an increase in the S1 internal energy, suggesting that the H atom tunneling dissociation reaction from OH might contribute less compared to the internal conversion, although it is not clear at the present time whether or not the sharp increase of the S1 relaxation rate in the high internal energy region of 3-CP (>1500 cm-1) is entirely due to that of the internal conversion. The fact that the internal conversion is facilitated by the Cl substitution implies that the energetic location of the S1/S0 conical intersection should have been strongly influenced by chlorine substitution on the aromatic ring. The approximate energetic location of the saddle point of the S1(ππ*)/πσCCl* conical intersection along the seam coordinate for CB or 3-CP could be inferred from the energy-dependent S1 lifetime measurements. It is discussed in comparison with the dynamic role of the S1(ππ*)/πσCCl* conical intersection, which is strongly influenced by the O-H···Cl intramolecular hydrogen bond in the rather complicated yet ultrafast S1 relaxation dynamics of the cis-2-CP. The S1 lifetimes of 3-CP·H2O and 2-CP·H2O reveal the importance of the conformational structures, especially in terms of the intramolecular hydrogen bonding.

Probing the Intramolecular Folding of Nucleic Acids with Native Ion Mobility Mass Spectrometry: Strategies and Caveats.

The goal of native mass spectrometry is to obtain information on noncovalent interactions in solution through mass spectrometry measurements in the gas phase. Characterizing intramolecular folding requires using structural probing techniques such as ion mobility spectrometry. However, inferring solution structures of nucleic acids is difficult because the low-charge state ions produced from aqueous solutions at physiological ionic strength get compacted during electrospray. Here we explored whether native supercharging could produce higher charge states that would better reflect solution folding, and whether the voltage required for collision-induced unfolding (CIU) could reflect preserved intramolecular hydrogen bonds. We studied pH-responsive i-motif structures with different loops, and unstructured controls. We also implemented a multivariate curve resolution procedure to extract physically meaningful pure components from the CIU data and reconstruct unfolding curves. We found that the relative unfolding voltages reflect to some extent, but not always unambiguously, the number of intramolecular hydrogen bonds that were present in solution. Reaching phosphate charging densities over 0.25 makes it easier to discriminate between structures, and the use of native supercharging agents is thus essential. We also uncovered several caveats in data interpretation: (1) when different structures (for example the i-motif with and without hairpin) unfold via different pathways, the unfolding voltages do not necessarily reflect the number of hydrogen bonds, (2) unstructured controls also undergo unfolding, and the base composition influences the unfolding voltage, (3) changing the solution pH also unexpectedly changed the unfolding voltage, and (4) the ion mobility patterns become more complicated when two structures are present simultaneously, such as an i-motif and a harpin, because of opposite effects on the collision cross section upon activation.

Synthesis, structure, DFT study and molecular docking inspection of spirobi[hexahydropyrimidine]-diones derivative

It has been established that three-component condensation of benzaldehyde, acetone and urea catalyzed H2SO4 leads to the formation of spirobi[hexahidropyrimidine]-dione derivatives. The structure of the synthesized compound has been proved by X-ray method. The results of the quantum theory of atom-in-molecule and noncovalent interaction index analysis showed no intramolecular hydrogen bonds in the molecule studied. However, it contains four N-H bonds and two C=O groups. Based on the result of the DFT-NBO analysis, it was the lone pairs of oxygen on the C=O group which are forming strong orbital interactions with the antibonding orbital of the C-N single bond. The molecular docking was performed to investigate potential binding interactions of the compound with four target proteins including 5I4T (HIV-1), 5R7Z, 6M71 and 6VYB (SARS-Cov-2). Additionally, in-silico drug-likeness and ADME studies suggested oral activity (violations ≤ 1) of scaffold and predicted to be actively effluxed by P-gp (PGP+).

Exploring and Regulating Heteroatom-Electronegativity-Associated with Ring Aromaticity and Excited State Intramolecular Proton Transfer Mechanism for Benzothiazole-Based Fluorophore.

A novel fluorophore 2-(2'-hydroxy-5'-benzaldehyde phenyl) benzothiazole (HBBT) with excited state intramolecular proton transfer (ESIPT) characteristics, showing good selectivity for Cu+/Cu2+ ions had been synthesized experimentally (Molecules 2022, 27, 7678). However, its ESIPT mechanism and fluorescent performance related to atomic substituents have not been investigated systematically. In this work, two HBBT derivatives, 2-(2'-hydroxy-5'-benzaldehyde phenyl)benzoimidazole (HBBI) and 2-(2'-hydroxy-5'-benzaldehyde phenyl)benzopyrrole (HBBP), were obtained by respectively using -NH and -CH2 groups in place of the sulfur atom in the thiazole ring. The absorption/emission spectra and ring aromaticity as well as ESIPT processes of HBBT and its derivatives were studied using density functional theory (DFT) and time-dependent DFT (TD-DFT). The simulated absorption and fluorescence wavelengths of HBBT agreed well with the corresponding values obtained in the experiment. According to the analyses of geometry structures, electron densities, and infrared vibration frequencies, the intramolecular hydrogen bond becomes stronger upon light excitation. The frontier molecular orbitals were analyzed via establishing potential energy curves, and the ESIPT behavior was described deeply. Obviously, the NH-substitution makes ring 4 more aromatic, while the CH2-substitution changes ring 4 from aromatic to antiaromatic. The ESIPT process helps to alleviate the excited state antiaromaticity. The greater the antiaromaticity of the S1 state normal form, the higher the barrier of ESIPT.

DFT-SCRF Calculations of Nitrogen Isotopic Reduced Partition Function Ratios for Amino Acids in Aqueous Solution at pH 7.4.

Using the self-consistent reaction field (SCRF) method, the nitrogen isotopic reduction partition function ratio (RPFR), a fundamental physical quantity for theoretical consideration of equilibrium isotope effects, was evaluated by density functional theory (DFT) for 20 proteinogenic and two related amino acids under physiological conditions at pH 7.4. At this pH value, all amino acids were of the zwitterion-type form with α-NH3+ and α-COO- groups, regardless of the net charge of -1 (monoanion), 0 (zwitterion), or +1 (monocation). The largest RPFR value by far was for proline (Pro). This is due to the fact that the nitrogen atom of Pro has two C-N bonds and two N-H bonds, whereas the α-nitrogen atoms of other amino acids form one C-N bond and three N-H bonds. There was a clear correlation between the RPFR value of α-nitrogen and the distance of the N-H covalent bond of the hydrogen atom involved in the formation of the intramolecular hydrogen bond (HB); the stronger the intramolecular HB, the lower the RPFR value of α-nitrogen. It was suggested that equilibrium isotope effects were partially responsible for the nitrogen isotope fractionation in the enzymatic glutamic acid/aspartic acid transamination and in ammonia assimilation during the formation of glutamine from glutamic acid.

Cholesterol Conjugated Elastin-like Recombinamers: Molecular Dynamics Simulations, Conformational Changes, and Bioactivity.

Current models for elastin-like recombinamer (ELR) design struggle to predict the effects of nonprotein fused materials on polypeptide conformation and temperature-responsive properties. To address this shortage, we investigated the novel functionalization of ELRs with cholesterol (CTA). We employed GROMACS computational molecular dynamic simulations complemented with experimental evidence to validate the in silico predictions. The ELRCTA was biosynthesized and characterized by using fluorescence assays, circular dichroism, dynamic light scattering, and differential scanning calorimetry. The in silico and in vitro data showed that CTA promotes the formation of intramolecular hydrogen bonds that favor β-sheet secondary structures. Compared with an unmodified ELRVKV, CTA enhanced the hydrophobicity and stability of the system, allowing the formation of monodisperse nanoaggregates at physiologically relevant temperatures. Importantly, calorimetry assays revealed that ELRCTA interacted and intercalated with the lipid bilayers of the DPPC liposomes. To demonstrate the implications of these changes for biomedical applications, ELRCTA and DPPC-ELRCTA hybrid nanoparticles were tested with cancer and immune cell lines. Interactions with the cell membranes demonstrated a synergistic effect of the composition and size of the modified recombinamer aggregates on the internalization. The results indicated the potential use of ELR-based nanoparticles for localized and systemic drug delivery. This work sets a new precedent to design elastin-inspired biomaterials with predictable self-assembly properties and develop novel drug delivery strategies.

Controlled Helical Organization in Supramolecular Polymers of Pseudo-Macrocyclic Tetrakisporphyrins.

Tetrakisporphyrin monomers with amino acid side chains at each end form intramolecular antiparallel hydrogen-bonds to adopt chirally twisted pseudo-macrocyclic structures that result in right-handed and left-handed (P)- and (M)-conformations. The pseudo-macrocyclic tetrakisporphyrin monomers self-assembled to form supramolecular helical pseudo-polycatenane polymers via head-to-head complementary dimerization of the bisporphyrin cleft units in an isodesmic manner. The formation of one-handed supramolecular helical pseudo-polycatenane polymers was confirmed by circular dichroism (CD) spectroscopy. The methyl and iso-propyl groups at the stereogenic center greatly enhanced the induced circular dichroism in the Soret bands of the supramolecular helical pseudo-polycatenane polymers. The induced CDs were reduced upon the introduction of large iso-butyl and tert-butyl groups. Atomic force microscopy revealed well-grown and long supramolecular helical pseudo-polycatenane polymer chains with chain lengths in the range of 361 to 13.6 nm. The right-handed helical chains were established by the self-assembly of the right-handed (P)-conformation of the pseudo-macrocyclic monomer.

Theoretical Study on Intramolecular Hydrogen Bonds of Flavonoid Cocrystals.

This study investigates the role of intramolecular hydrogen bonds in the formation of cocrystals involving flavonoid molecules, focusing on three active pharmaceutical ingredients (APIs): chrysin (CHR), isoliquiritigenin (ISO), and kaempferol (KAE). These APIs form cocrystals with different cocrystal formers (CCFs) through intramolecular hydrogen bonding. We found that disruption of these intramolecular hydrogen bonds leads to decreased stability compared to molecules with intact bonds. The extrema of molecular electrostatic potential surfaces (MEPS) show that flavonoid molecules with disrupted intramolecular hydrogen bonds have stronger hydrogen bond donors and acceptors than those with intact bonds. Using the artificial bee colony algorithm, dimeric structures of these flavonoid molecules were explored, representing early-stage structures in cocrystal formation, including API-API, API-CCF, and CCF-CCF dimers. It was observed that the number and strength of dimeric interactions significantly increased, and the types of interactions changed when intramolecular hydrogen bonds were disrupted. These findings suggest that disrupting intramolecular hydrogen bonds generally hinders the formation of cocrystals. This theoretical study provides deeper insight into the role of intramolecular hydrogen bonds in the cocrystal formation of flavonoids.

Supramolecular Co (II) Complex Fabricated From Adenine Derivative: Synthesis, Crystal Structure, Hirshfeld Surface, DFT Optimization, Anticancer, and Molecular Docking Studies

ABSTRACTThis article presents the synthesis of a novel mononuclear Co (II) complex [Co(9‐BuA)2Cl2] (1), its characterization, supramolecular packing pattern, theoretical calculations, anticancer properties, and molecular docking studies. Complex 1 was generated from 9‐butyl adenine (9‐BuA) building block and characterized by spectroscopic methods (FT‐IR, mass, elemental analysis) and single crystal X‐ray diffraction analysis. The cobalt (II) ion in complex 1 is distorted in its tetrahedral environment. The Co+2 is coordinated to the two rare N1 binding sites of the pyrimidinate moiety of two 9‐BuA ligands and two chlorine atoms occupying the axial positions. Both intramolecular and intermolecular hydrogen bonds support the formation of supramolecular assembly and stabilize the crystal structure. The nature of the intermolecular interactions in the supramolecular network was also decoded by Hirshfeld surface analysis and molecular surface contours (dnorm). The percentage contributions are represented by 2D fingerprint plots. The average energy between dimers was determined by the energy framework analysis, and the crystal packing's three‐dimensional topology was also investigated. Density functional theory (DFT) has been used to ascertain the geometry and interactions in the complex. The cytotoxic effects of Co (II) complex 1 and corresponding 9‐BuA ligand were investigated in Dalton's lymphoma (DL) malignant cancer cells and on normal peripheral blood mononuclear cells (PBMCs) to evaluate their anticancer activity. Finally, molecular docking analyses have been carried out to analyze the nature of molecular interactions between Co (II) complex 1 and the receptor.

Hydrogen bond, protonation, and coordination-induced supramolecular chirality inversion in glutamide-based amphiphilic self-assembly

In this study, we have synthesized two types of Y-shaped chiral amphiphiles, namely L-BG and L-PG, with a benzene or pyridine ring at the terminal position, respectively. The optimized conformations of both amphiphiles indicate the presence of intramolecular interactions. In dimethylformamide (DMF) solution at the monomeric state, both amphiphiles exhibit positive cotton effects; however, in DMF/H2O mixed solution, the cotton effects are inverted. Molecular dynamics simulations reveal that both intermolecular and intramolecular hydrogen bonds facilitate the inversion of supramolecular chirality. Additionally, protonation and coordination of L-PG assembly results in chirality inversion and transformation of emission. This study emphasizes the significance of both inter- and intramolecular hydrogen bonds in the assembly process, providing insights into stimuli-responsive chiral supramolecular materials.

Tetrazaisoindigos:Serpentine Syntheses and Their Expected and Unexpected Photophysical and Electronic Properties.

Isoindigo, an electron-withdrawing building block for polymeric field-effect transistors, has long been considered to be non-fluorescent. Moreover, using electron-deficient heterocycle to replace the phenyl ring in the isoindigo core for better electron transport behaviour is synthetically challenging. Here we report the syntheses of a series of tetrazaisoindigos, including pyrazinoisoindigo (PyrII), pyrimidoisoindigo (PymII) and their hybrid (PyrPymII), and the investigation on their photophysical and electric properties. Proper flanking groups need to be chosen to stabilize these highly electron-deficient bislactams. Both PyrII and PymII derivatives show lower LUMO energy levels than that of naphthalene bisimide (NDI). Interestingly, PyrII is instinctively unstable and can be easily reduced, while both PymII derivatives are stable. More surprisingly, PymII derivatives are highly fluorescent and their photoluminescence quantum yields are around 40 %, 133 times higher than that of reported isoindigo derivatives. UV-vis spectroscopic results and theoretical calculations show that strong intramolecular hydrogen-bond exists in PymII, which prohibits it from non-radiative decay and accounts for its fluorescent behaviour. PymII derivatives are n-type semiconductors, while Ph-PyrII and the hybrid show balanced ambipolar charge transport behaviour, all among the best isoindigo derivatives. Our study not only discloses the structure-property relationship of tetrazaisoindigos, but also provides novel electron-deficient monomers for conjugated polymers.

Fast Production of Covalent Organic Frameworks for Covalent Enzyme Immobilization with Boosted Enzymatic Catalysis by Solar‐Driven Photothermal Effect

AbstractDeveloping new enzyme‐immobilization systems to stabilize their dynamic structures and meanwhile enhance their catalytic activity is of great significance but very challenging. Herein, we design and fabricate a class of robust mesoporous covalent organic frameworks (COFs) via Michael addition‐elimination reaction. It is found that highly crystalline COFs can be produced in 10 min, which is attributed to the promoting effect of the intramolecular hydrogen bond activation. The COFs rich in hydroxyl groups can be facilely post‐modified by epibromohydrin to covalently immobilize enzymes with both high loading and activity. Furthermore, we create a solar‐driven photothermal‐promoted strategy by introducing photoactive azo groups to COF carriers, which can boost the enzyme catalytic performance (lipase) with much higher conversion of various racemic substrates and chiral resolution upon solar light irradiation. The heterogeneous biocatalysts also demonstrate exceptional reusability and stability. This work provides a green and energy‐efficient approach to facilitate the scale application of enzyme‐immobilized biocatalysts.

Fast Production of Covalent Organic Frameworks for Covalent Enzyme Immobilization with Boosted Enzymatic Catalysis by Solar-Driven Photothermal Effect.

Developing new enzyme-immobilization systems to stabilize their dynamic structures and meanwhile enhance their catalytic activity is of great significance but very challenging. Herein, we design and fabricate a class of robust mesoporous covalent organic frameworks (COFs) via Michael addition-elimination reaction. It is found that highly crystalline COFs can be produced in 10 min, which is attributed to the promoting effect of the intramolecular hydrogen bond activation. The COFs rich in hydroxyl groups can be facilely post-modified by epibromohydrin to covalently immobilize enzymes with both high loading and activity. Furthermore, we create a solar-driven photothermal-promoted strategy by introducing photoactive azo groups to COF carriers, which can boost the enzyme catalytic performance (lipase) with much higher conversion of various racemic substrates and chiral resolution upon solar light irradiation. The heterogeneous biocatalysts also demonstrate exceptional reusability and stability. This work provides a green and energy-efficient approach to facilitate the scale application of enzyme-immobilized biocatalysts.

Template Synthesis of the Iron(III) Complex with the Ligands Based on Acylpyrazolonepyridines

The reaction of new bidentate ligand, 1-(5-hydroxy-1-methyl-3-(pyridin-2-yl)-1Н-pyrazol-4-yl)ethan-1-one (L), with iron(III) chloride affords the mononuclear iron(III) complex FeL₂Cl₃, which is characterized by XRD (CIF file CCDC no. 2309481). The intramolecular hydrogen bond between the protonated pyridyl and acetyl groups in ligand L, which exists in the crystal as a zwitterion, provides the formation of rarely met iron complexes in which the β-diketonate fragment coordinates via the η1 mode. A similar coordination mode along with a possibility of a more favorable η2 coordination provides new possibilities for the design of heteropolynuclear compounds of various structures used in the fabrication of molecular devices of data storage and processing.

Twisted Amide-Mediated Peptide Synthesis.

A robust, practical, and sustainable isomerization-suppressed peptide bond formation via acyl sulfonamide, a twisted amide, is disclosed. Tosyl isocyanate and pentafluorobenzyl bromide were applied in combination to activate the peptide C-terminus, which then reacted with an amine to yield an elongated peptide with high stereochemical purity. Careful analysis of NMR spectra of the active intermediate revealed the presence of an intramolecular hydrogen bond, suggesting that the hydrogen bond suppressed Cα-epimerization during amidation. The isomerization suppression by the intramolecular hydrogen bond is expected to be effective even under high dilution conditions, making the present method a powerful tool for the synthesis of complex macrocyclic peptides. In addition to peptide synthesis, the developed synthetic entry to twisted amides can be applied to the investigation of transition metal-catalyzed N-C bond activation. Moreover, the application to the N-C bond activation returned insight into peptide synthesis, leading to the use of sulfonamide as a protecting group of carboxylic acid that can be orthogonally removed in the presence of other conventional protecting groups.

Isomerism in Phenyl 2‐Pyridyl Ketoxime Metal Complexes

AbstractThe octahedral complex [RhCl2(ppkoH)(ppko)] (1) was obtained from the reaction between RhCl3 and phenyl 2‐pyridyl ketoxime (ppkoH). Attempts to prepare the corresponding octahedral platinum compound from K2PtCl6 gave instead the square planar [Pt2+(ppko)2] (2), but when the halogen was changed to bromine, the octahedral [Pt4+Br2(ppko)2] (3) was formed. The crystal structures were determined by X‐Ray crystallography. All the compounds have two N,N‐chelating oxime ligands. In 1, one of them is deprotonated, while in 2 and 3 both ligands are deprotonated. Compounds 1 and 3 have two halogen ligands in trans position. In 1 the oxime groups are situated mutually in cis position with an intramolecular hydrogen bond between the two N−O(H) groups. The formation of 2 involves reduction of the platinum metal and the complex has oximes in trans position to each other. Compound 3 has an all‐trans geometry. Since octahedral and square planar compounds have a possibility to isomerism, we studied the relative stability of different geometries by DFT calculations. A mixture of isomers is likely to be formed in the reactions, but the most stable form was found to crystallize. The properties of the electron density in the preferred isomers were also investigated via QTAIM methods.

Screening and evaluation of phase change absorbents by molecular polarity index: Experimental and quantum chemical calculation studies

Phase change absorbents have recently received increasing attention due to their potential to reduce the energy penalty of CO2 capture. However, its complex composition makes the prediction of phase separation performance difficult. Phase separation behavior and phase separation rate have been investigated for the amine-aqueous 5.0 M amine blends by experimental and quantum chemical calculations (including MPI, hydrogen bonds and Gibbs free energy). The different phase behaviors upon CO2 absorption were discussed and well explained by the polarity change of components and the reaction products. A defined MPI value of tertiary amines was recommended to predict the immiscible type (MPI > 10.55 Kcal/mol), phase separation type (9.00 Kcal/mol < MPI < 10.08 Kcal/mol), and miscible type (MPI < 6.74 Kcal/mol). The electron density at the critical point of hydrogen bonds and interaction region indicators were employed to visually evaluate the influence of intramolecular and intermolecular hydrogen bonds on phase separation behaviors. The results show that the presence of excessive hydrogen bonds decreased the phase separation capacity. Furthermore, the relationship between the MPI, the Gibbs free energy of the proton transfer process and the phase separation time were explored. The increase of MPI caused by the tertiary amines can enhance the stability of the final product, delay the appearance of the phase separation peak and reach a maximum phase separation time of 230 min. Therefore, this study is significant for the screening and evaluation of efficient phase change absorbents with good potential for industrial applications in CO2 capture.

Tactfully regulating the ESIPT mechanism of novel benzazolyl-4-quinolones fluorophore by atomic electronegativity

The effects of atomic electronegativity (O, S and Se) on the excited state intramolecular proton transfer (ESIPT) behavior of fluorescent benzazolyl-4-quinolones derivatives have been investigated theoretically. Analysis of structure parameters and infrared vibrational spectra indicate that the intramolecular hydrogen bonds (O1H1⋯N1) are gradually strengthened in the first (S1) excited state as the atomic electronegativity diminishes (O → S → Se). The topological parameters, reduced density gradient (RDG) scatter plots and interaction region indicator (IRI) isosurface further confirm our results. The energy gap of molecular orbitals reflect that the less atomic electronegativity prompt greater excited state reactivity. In addition, the constructed potential energy curves (PECs) reveal that Se substituent has lower potential barrier (0.42 kcal/mol), which is more likely to accelerate the occurrence of ESIPT process. These results show that the atomic electronegativity helps to regulate the ESIPT process, which will pave the way for the design and synthesis of ESIPT-based fluorophores in future.

Vicinal Combination of N—NH2 and C—NO2 Benefitting for Low Sensitivity and High Energy Azole Molecules: A Strategy Developed from Isomerization

It is nowadays challenging to create low sensitivity and high energy molecules (LSHEMs), largely restricted by the high complexity and difficult interpretation of composition-structure-property relationships of energetic materials. In the present theoretical modeling work on energetic materials, we propose a strategy for constructing LSHEMs based on energetic azole isomerism to reduce the molecular complexity while maintain composition. That is, we firstly find that the vicinal combination of N—NH2 and C—NO2 is an effective unit to enhance both energy and molecular stability of azoles. The advantage of the combination largely stems from the oxygen balance improvement to be close to zero to elevate reaction heat and packing density, and the intramolecular hydrogen bond formation to enhance molecular stability. Thus, this unit can be widely considered in constructing N-rich low sensitivity and high energy azole molecules. In addition, we confirm that the N—NO2 generally seriously do harm to the molecular stability of azoles, especially in the case of the existence of steric effect around it.

Synthesis, structural characterization, and ADMET analysis of new pyrazol-pyrimidine derivatives

New pyrazol-pyrimidine derivatives were obtained starting from pyrazolone, barbituric acid, and different substituted benzaldehydes, by reflux in a mixture of ethanol/water (1:1) as a solvent and without any catalyst. All isolated products were characterized by employing various techniques, including melting point, elemental analysis, IR, and NMR spectroscopy. Experimentally obtained IR and NMR spectra of all pyrazol-pyrimidine derivatives were compared to the simulated ones acquired with TD-DFT. The obtained results show that there is a very good agreement between the theoretical and recorded spectra. Moreover, the structure of 5-((4-fluorophenyl)(5-methyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)methyl)-6-hydroxypyrimidine-2,4(1H,3H)-dione was explained using single-crystal X-ray diffraction analysis. It was shown that a barbiturate ring plays a dominant role in the formation of strong intramolecular hydrogen bond with pyrazole moiety and the mutual interconnection of molecules in crystal packing. Pyrazol-pyrimidine derivatives have the capacity to exist in various keto and enol tautomer forms which can be converted into the matching zwitterion. This finding is confirmed by experimental and theoretical results. Additionally, this study explores the pharmacokinetic profile of obtained compounds and the inhibitory activities of selected compounds against Human Carbonic Anhydrase II using molecular docking simulations.