Structural Moieties Research Articles

Liquid-Phase NMR of Humic and Fulvic Acids.

Present review focuses on the most recent advances in the NMR of the coal-derived humic and fulvic acids, covering exclusively the results of the liquid-phase NMR and leaving apart an overwhelming amount of publications dealing with the solid-state NMR investigations in this field (the latter are comprehensively reviewed elsewhere). Owing to the complexity of humic and fulvic acids together with other coal-derived products, their 1H and 13C NMR spectra consist of a number of overlapping signals belonging to different hydrocarbon types. Comprehensive studies of humic and fulvic acids by means of NMR revealed characteristic functional groups of their composition together with spectral regions in which they resonate. Quantitative 1H and 13C NMR spectra characterize aromatic and saturated carbons spread over many structural moieties, which provides a solid guideline into molecular structure of humic and fulvic acids together with parent coal-derived products. Nowadays, quantitative 13C NMR measurements yield information about a variety of structural parameters such as functional group distribution, aromaticity, degree of condensation of aromatic rings, and medium chain lengths together with many other more specific parameters. The structural NMR studies of the coal-derived products are developing on a background of a marked progress in experimental and computational NMR. Discussed in the present review are the most recent advances in the liquid-state NMR studies of the coal-derived humic and fulvic acids together with their processing products.

Identifications of False Positives Amongst Sodium(I) Cations in Protein Three-Dimensional Structures—A Validation Approach Extendible to Any Alkali or Alkaline Earth Cation and to Any Monoatomic Anion

Validation of the data deposited in the Protein Data Bank is of the upmost importance, since many other databases, data mining processes, and artificial intelligence tools are strictly grounded on them. The present paper is divided into two parts. The first part describes and analyzes validation methods that have been designed and used by the structural biology community. Everything began with the Ramachandran plot, with its allowed and disallowed types of backbone conformations, and evolved in different directions, with the inclusion of additional stereochemical features, distributions’ analyses of structural moieties, and scrutiny of structure factor amplitudes across the reciprocal lattice. The second part of the paper is focused on the largely unexplored problem of the high number of false positives amongst the sodium(I) cations observed in protein crystal structures. It is demonstrated that these false positives, which are atoms wrongly identified with sodium, can be identified by using electrostatic considerations and it is anticipated that this approach can be extended to other alkali and alkaline earth cations or to monoatomic anions. In the end, I think a global initiative, accessible to all volunteers and possibly overseen by the Protein Data Bank, should take the place of the numerous web servers and software applications by providing the community with a select few reliable and widely accepted tools.

Erinacenones A–L: Twelve New Isoindolinone Alkaloids from the Edible and Medicinal Mushroom Hericium erinaceus

A total of twelve previously unreported isoindolin-1-one compounds, erinacenones A–L (1–12), were isolated from liquid cultures of the medicinal fungus Hericium erinaceus. Their structures were elucidated based on spectroscopic data analysis. The absolute configuration of 12 was determined by comparing its optical rotations with values reported in the literature. The most distinctive feature of these compounds is that their nitrogen atoms are connected to different parts of the special structure moieties. Among them, compounds 3 and 4, as well as 10 and 11, are two pairs of isomers differing only by a small change in the position of one double bond. Compounds 4 and 5 were found to show cytotoxic activities, with IC50 values of 24.7 and 18.4 μM, respectively, against MCF-7 cell lines.

The vibrational circular dichroism exciton coupling in single-bond C–O stretching vibrations of p-menthene derivatives

The exciton coupling (EC) phenomenon becomes a valuable tool for the absolute configuration (AC) determination of organic molecules when an interaction between two strategically located chromophores in a molecule is evidenced by circularly polarized radiation. Besides the widely used exciton chirality method in electronic circular dichroism, the technique has been also developed for vibrational circular dichroism (VCD). Notably, the information provided by CO stretching vibrations (1680−1800 cm−1) in VCD have demonstrated high applicability. However, reported theoretical approaches have warned about the adequate interpretations of the EC phenomenon since analyzed bisignate bands could be associated with other vibrations. The current paper experimentally addresses the problem to expand the criteria for using EC data in AC determinations. Herein, the VCD exciton coupling (VCDEC) methodology is extended to the analysis of C–O stretching vibrations (1100–1300 cm−1) to uncover their possible use in AC determinations, as well as to reveal the specific contribution of the EC related to C–O vibrations when experimental parameters are considered. To this aim, naturally occurring p-menthene alcohols 1–4 isolated from Ageratina glabrata were previously used to prepare acetates 5 and 6, and acetonides 7 and 8, and now, to prepare carbonates 9–11. Density functional theory (DFT) calculations, including the IR and VCD spectra of the seven derivatives (5–11), were carried out to reinforce the conformational and configurational analysis, while the experimental VCD spectra of 5–7, 9, and 11 demonstrated the presence of C–O couplets. A systematic analysis of these bands, including the Δε value at alpha and beta state (Δεα, Δεβ, respectively), the amplitude of EC (A = ∑ǀΔεǀ) value, the couplet period (L =v‾Δεβ − v‾Δεα) value, the specific area of C–O at couplet (S = Σf(x)(u2)), and the percentage of area related to EC from C–O (S%) were considered. These experimental results were directly related to dihedral angles (θ) from simplistic models to establish the AC. The results suggested that A, Cp, S, and S% parameters are deeply related to the nature of the chromophores. Thereby, adequate molecular structural moieties should be chosen for AC determination when using the EC methodology.

Exploration and characterization of the antimalarial activity of cyclopropyl carboxamides that target the mitochondrial protein, cytochrome b

Drug resistance against antimalarials is rendering them increasingly ineffective and so there is a need for the development of new antimalarials. To discover new antimalarial chemotypes a phenotypic screen of the Janssen Jumpstarter library against the P. falciparum asexual stage was undertaken, uncovering the cyclopropyl carboxamide structural hit class. Structure-activity analysis revealed that each structural moiety was largely resistant to change, although small changes led to the frontrunner compound, WJM280, which has potent asexual stage activity (EC50 40 nM) and no human cell cytotoxicity. Forward genetics uncovered that cyclopropyl carboxamide resistant parasites have mutations and an amplification in the cytochrome b gene. Cytochrome b was then verified as the target with profiling against cytochrome b drug-resistant parasites and a mitochondrial oxygen consumption assay. Accordingly, the cyclopropyl carboxamide class was shown to have slow-acting asexual stage activity and activity against male gametes and exoerythrocytic forms. Enhancing metabolic stability to attain efficacy in malaria mouse models remains a challenge in the future development of this antimalarial chemotype.

Identification of complexes formed between sulphur mustards and arsenic-containing chemical warfare agents

Large quantities of toxic chemical warfare material, such as mixtures of sulphur mustard (HD) and arsenic-containing chemical warfare agents (As-CWAs) have been submerged in the Baltic Sea region after World War II. Little is known about the possible reactivity between HD and As-CWAs. In this study, we used simple reaction mixtures and ultra-high performance liquid chromatography combined with mass spectrometric techniques to study the reactivity of HD and the half-mustard 2-chloroethyl ethyl sulphide (CEES) with As-CWAs. Altogether 22 novel As-CWA-HD- and As-CWA-CEES-complexes were identified. Eight of the As-CWA-HD-complexes were also detected in environmental samples collected from known CWA dumping sites in the Baltic Sea region. Because the As-CWA-HD- and As-CWA-CEES-complexes have structural moieties of both S-mustards and As-CWAs, they might have toxic properties of both CWA-types. Therefore, their occurrence in the environment is concerning and their potential negative effect on the wellbeing of marine biota and humans should be investigated in the future. This is the first time alkylation of As-CWAs is reported, providing new knowledge on the reactivity of S-mustards. The results increase the understanding of the environmental fate of HD and is valuable for the assessment of the environmental threat of sea-dumped CWAs.

A Highly Atom-Efficient Prodrug Approach to Generate Synergy between H2S and Nonsteroidal Anti-inflammatory Drugs and Improve Safety.

Efforts to synergize hydrogen sulfide (H2S) with NSAIDs have faced challenges due to complex structural entities and independent release kinetics. This study presents a highly atom-efficient approach of using a thiocarboxylic acid (thioacid) as a novel H2S releasing precursor and successfully employs it to modify NSAIDs, which offers several critical advantages. First, thioacid-modified NSAID is active in inhibiting cyclooxygenase, sometimes with improved potency. Second, this prodrug approach avoids introducing extra structural moieties, allowing for the release of only the intended active principals. Third, the release of H2S and NSAID is concomitant, thus optimally synchronizing the concentration profiles of the two active principals. The design is based on our discovery that esterases can directly and efficiently hydrolyze thiocarboxylic acids, enabling controlled release H2S. This study demonstrates the proof of principle through synthesizing analogs, assesses release kinetics, enzyme inhibition, and pharmacological efficacy, and evaluates toxicity and gut microbiota regulation in animal models.

DNP enhanced solid-state NMR – A powerful tool to address the surface functionalization of cellulose/paper derived materials

This concept summarizes recent advances in development and application of DNP enhanced multinuclear solid-state NMR to study the molecular structure and surface functionalization of cellulose and paper-based materials. Moreover, a novel application is presented where DNP enhanced 13C and 15N solid-state NMR is used to identify structure moieties formed by cross-linking of hydroxypropyl cellulose. Given these two aspects of this concept-type of article, we thus combine both, a review on recent findings already published and unpublished recent data that complement the existing knowledge in the field of characterization of functional lignocellulosic materials by DNP enhanced solid-state NMR.

Induced nematic phase with improved thermal characteristics for new maleic anhydride derivatives

A new group of liquid crystalline materials, denoted as (E)-4-(((4-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)phenyl)imino)methyl)phenyl 4-(alkoxy)benzoate (In), was synthesized from maleic anhydride and investigated for their mesomorphic and optical properties. This group includes four derivatives with different flexible chain lengths (6, 8, 10, and 12 carbons) attached to the phenyl ring near the ester bond. Polarized optical microscopy (POM) and differential scanning calorimetry (DSC) were carried out to examine their mesophase characteristics. The thermogravimetric analysis (TG) was employed to evaluate the thermal stability of the homolog set (I6). Molecular structures were characterized using NMR, FT-IR, and elemental analysis techniques. All the produced derivatives show enantiotropic nematic mesophases, according to the results. The range and stability of the produced nematic phase are affected by the introduction of the heterocyclic maleic anhydride unit into the molecular structure. Furthermore, comparison with short-size documented derivatives establishes that the addition of extra phenyl azomethine moiety in the molecular structure induces the formation of nematic phases.

Preliminary Study on Polymerization between Hemoglobin and Enzymes during the Preparation of PolyHb-SOD-CAT-CA.

The objective of this study was to explore the influence of different factors on the aggregation effect on hemoglobin (Hb) and enzymes during the preparation of Polyhemoglobin-Superoxide dismutase-Catalase-Carbonic anhydrase (PolyHb-SOD-CAT-CA). Several factors including temperatures, pH values, Glutaraldehyde (GDA) amounts and enzymes amounts were investigated systematically to study their effects on the enzymes recoveries and polymerization rates including the Superoxide dismutase (SOD), Catalase (CAT) and Carbonic anhydrase (CA), as well as their effects on the molecular weight distribution of PolyHb-SOD-CAT-CA. Then the oxygen affinity and methemoglobin (MetHb) contents of obtained PolyHb-SOD-CAT-CA were measured to evaluate the effects of enzyme crosslinking on the properties of Polyhemoglobin (PolyHb) moieties in the molecular structure of obtained PolyHb-SOD-CAT-CA conjugate. The results showed that the enzyme recoveries and polymerization rates could be decreased with the temperatures increasing and could be generally kept stable in the physiological pH conditions, but presented only slight changes among the investigated enzyme amounts ranges. Although the GDA concentration increasing could promote the enzyme polymerization rates, the enzyme recoveries decreased in whole. The polymerization rate and molecular size of PolyHb-SOD-CAT-CA conjugate increased with the elevation of temperature and the concentration of GDA. Lastly, the P50 values, Hill coefficients, and MetHb contents of PolyHb-SOD-CAT-CA conjugate with different enzyme crosslinking degrees exhibited no obvious differences with each other. In conclusion, the polymerization reactions between enzymes and Hb molecules could be remarkably affected by temperatures, pH values, and GDA amounts, and the enzyme crosslinking presented no obvious effects on the Hb properties, especially about the oxygen affinity and oxidation degrees.

13C CSA Tensors and Orientational Order of Model and Dimer Mesogens Comprising of Phenyl Benzoate.

A Model mesogen and its symmetrical Dimer made up of phenyl benzoate core unit are investigated by 13C NMR spectroscopy. The existence of layer order in smectic A and smectic C phases of Dimer mesogen is established by powder X-ray diffraction. The chemical shift anisotropy (CSA) tensors of Model mesogen are determined by 2D separation of undistorted powder patterns by effortless recoupling (SUPER) experiment and are utilized for calculating the order parameters employing the alignment-induced chemical shifts (AIS). Additionally, 2D separated local field (SLF) NMR is availed for extracting 13C-1H dipolar couplings for both mesogens and used for computing the order parameters. A good agreement in the order parameters calculated from 13C-1H dipolar couplings and AIS is observed. Accordingly, the main order parameter (Szz) for the phenyl rings of the Model mesogen is found to be in the range 0.54 - 0.82, and for the Dimer mesogen, the values span 0.64 - 0.82 across mesophases. Since the phenyl benzoate core unit is frequently employed structural moiety for constructing the main chain as well as side chain liquid crystalline polymers and liquid crystalline elastomers, the CSA tensors reported here will be of immense utility for the structural characterization of these materials.

Enhanced CO2 Reduction on a Cu-Decorated Single-Atom Catalyst via an Inverse Sandwich M-Graphene-Cu Structure.

The highly active and selective electrochemical CO2 reduction reaction (CO2RR) can be exploited to produce valuable chemicals and fuels and is also crucial for achieving clean energy goals and environmental remediation. Decorated single-atom catalysts (D-SACs), which feature synergistic interactions between the active metal site (M) and an axially decorated ligand, have been extensively explored for the CO2RR. Very recently, novel double-atom catalysts (DACs) featuring inverse sandwich structures were theoretically proposed and identified as promising CO2RR electrocatalysts. However, the experimental synthesis of DACs remains a challenge. To facilitate the fabrication and to realize the potential of these novel DACs, we designed a D-SAC system, denoted as M1@gra+Cuslab. This system features a graphene layer with a vacancy-anchored SAC, all stacked on a Cu(111) surface, thereby embodying a Cu slab-supported inverse sandwich M-graphene-Cu structure. Using density functional theory calculations, we evaluated the stability, selectivity, and activity of 27 M1@gra+Cuslab systems (M = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Nb, Mo, Ru, Rh, Pd, Ag, Cd, Hf, Ta, W, Re, Os, Ir, Pt, or Au) and showed five M1@gra+Cuslab (M = Co, Ni, Cu, Rh, or Pd) systems exhibit optimal characteristics for the CO2RR and can potentially outperform their SAC and DAC counterparts. This study offers a new strategy for developing highly efficient CO2RR D-SACs with an inverse sandwich structural moiety.

Synergistic scavenging of sulfamethoxazole and hexavalent chromium in groundwater sample induced by iron-char composites activated persulfate triggering dominant electron transfer process

Effectively scavenging combined pollutants in complex water matrix via dominant electron transfer pathway using modified zero-valent iron (ZVI) remains challenging. Herein, novel iron-based catalysts were synthesized using ball milling and pre-oxidation modified biochar (MOBC), which featured abundant pore structure and oxygen-rich functional moieties to support nZVI in activating persulfate (PS). The most suitable catalytic system achieved ultrafast simultaneous removal of 89.0 % of sulfamethoxazole (SMX) and nearly 100 % of hexavalent chromium (Cr(VI)) within 5 min (with nearly complete removal of SMZ and Cr(VI) in 60 min). By serving as an electron shuttle, MOBC700 could accelerate electron transfer from SMX to PS adsorbed on the nZVI1.0@MOBC700 for SMX decomposition, with reactive oxygen species (ROSs) also contributing. Moreover, nZVI facilitated the reduction of Cr(VI) adsorbed on nZVI1.0@MOBC700 through electron transfer. The dissolved Fe(II) generated via PS activation and Cr(VI) reduction further facilitated Cr(VI) removal from the solution, while the gradual consumption of excess Fe(II) ensured continued ROSs-mediated degradation of SMX. Additionally, the system also demonstrated resistance to interference from NO3-, CO32-, and humic acid, and was effective in remediating four different water samples. Overall, this study presents a promising method for designing iron-char composites to address combined antibiotic and heavy metal contamination in groundwater samples via dominant electron transfer process.

Template-independent synthesis and 3'-end labelling of 2'-modified oligonucleotides with terminal deoxynucleotidyl transferases.

Xenobiotic nucleic acids (XNAs) are artificial genetic polymers with altered structural moieties and useful features, such as enhanced biological and chemical stability. Enzymatic synthesis and efficient labelling of XNAs are crucial for their broader application. Terminal deoxynucleotidyl transferases (TdTs) have been exploited for the de novo synthesis and labelling of DNA and demonstrated the capability of recognizing various substrates. However, the activities of TdTs for the synthesis and labelling of commonly used XNAs with 2' modifications have not been systematically explored. In this work, we explored and demonstrated the varied activities of three TdTs (bovine TdT, MTdT-evo and murine TdT) for the template-independent incorporation of 2'-methoxy NTPs, 2'-fluoro NTPs and 2'-fluoroarabino NTPs into the 3' ends of single- and double-stranded DNAs and the extension of 2'-modified XNAs with (d)NTPs containing a natural or unnatural nucleobase. Taking advantages of these activities, we established a strategy for protecting single-stranded DNAs from exonuclease I degradation by TdT-synthesized 2'-modified XNA tails and methods for 3'-end labelling of 2'-modified XNAs by TdT-mediated synthesis of G-quadruplex-containing tails or incorporation of nucleotides with a functionalized nucleobase. A DNA-2'-fluoroarabino nucleic acid (FANA) chimeric hydrogel was also successfully constructed based on the extraordinary activity of MTdT-evo for template-independent FANA synthesis.

Mechanism of allosteric inhibition of human p97/VCP ATPase and its disease mutant by triazole inhibitors

Human p97 ATPase is crucial in various cellular processes, making it a target for inhibitors to treat cancers, neurological, and infectious diseases. Triazole allosteric p97 inhibitors have been demonstrated to match the efficacy of CB-5083, an ATP-competitive inhibitor, in cellular models. However, the mechanism is not well understood. This study systematically investigates the structures of new triazole inhibitors bound to both wild-type and disease mutant forms of p97 and measures their effects on function. These inhibitors bind at the interface of the D1 and D2 domains of each p97 subunit, shifting surrounding helices and altering the loop structures near the C-terminal α2 G helix to modulate domain-domain communications. A key structural moiety of the inhibitor affects the rotameric conformations of interacting side chains, indirectly modulating the N-terminal domain conformation in p97 R155H mutant. The differential effects of inhibitor binding to wild-type and mutant p97 provide insights into drug design with enhanced specificity, particularly for oncology applications.

How pulse electric field treatment affects anti-nutritional factors and plant protein digestibility: A concise review

Consumption of foods rich in anti-nutritional factors (ANFs) can lead to inadequate absorption of vitamins and minerals. Pulsed electric field (PEF) treatment is a non-thermal food processing technology that uses short bursts of high voltage electric fields to induce structural modifications in biomolecules, including proteins, through electrochemical reactions and polarization of structural moieties. PEF offers potential benefits in enhancing the nutritional quality of food products by altering the structure and function of ANFs. However, the effects of PEF on ANFs in food have not been well established. Additionally, PEF-treated samples may undergo protein structural orientation modification due to electroporation and free radical species, potentially unfolding the native structure and influencing protein digestibility. Moreover, by increasing the mass transfer rate, electroporation can enhance the extraction of the initially trapped fractions into the solvent medium, which may include target compounds that affect protein functionality and digestibility. However, the protein digestibility of PEF-treated food products is yet to be thoroughly explored. Therefore, this review objectively investigates the possible mechanisms involved and the effectiveness of PEF in reducing different ANFs and modifying plant protein digestibility. This review also provides in-depth information about the possible applications of PEF-treated food items in the food industry.

Recent advances in liquid-phase NMR of the coal-derived products.

Present review focuses on the most recent advances in a liquid-phase nuclear magnetic resonance (NMR) of the coal-derived products-coal tar pitches, asphaltenes, and humic and fulvic acids, covering exclusively the results in the liquid-phase NMR studies leaving apart an overwhelming amount of publications dealing with the solid-state NMR investigations in this field (which are comprehensively reviewed elsewhere). Owing to the complexity of the coal-derived products, their 1H and 13C NMR spectra consist of a number of overlapping signals belonging to different hydrocarbon types. Comprehensive studies of coal tar pitches, asphaltenes, and humic and fulvic acids by means of NMR over the past several decades revealed characteristic functional groups of those fractions together with spectral regions in which they resonate. Quantitative 1H and 13C NMR spectra characterize aromatic and saturated carbons spread over many structural moieties, which provides a solid guideline into molecular structure of the coal-derived products. Nowadays, quantitative 13C NMR measurements yield information about a variety of structural parameters such as functional group distribution, aromaticity, degree of condensation of aromatic rings, and medium chain lengths together with many other more specific parameters. The structural NMR studies of coal and coal-derived products are developing on a backdrop of a marked progress in computational NMR. At present, we are witnessing an unprecedentedly fast development of theoretical and computational methods in the field of NMR spectroscopy. Discussed in the present review are the most recent advances in the NMR studies of the processing products of peat, lignite or brown coal, anthracite or hard coal, and graphite in solution, like coal tar pitches, asphaltenes, and humic and fulvic acids.

Three-dimensional saturated C(sp3)-rich bioisosteres for benzene.

Benzenes, the most ubiquitous structural moiety in marketed small-molecule drugs, are frequently associated with poor 'drug-like' properties, including metabolic instability, and poor aqueous solubility. In an effort to overcome these limitations, recent developments in medicinal chemistry have demonstrated the improved physicochemical profiles of C(sp3)-rich bioisosteric scaffolds relative to arenes. In the past two decades, we have witnessed an exponential increase in synthetic methods for accessing saturated bioisosteres of monosubstituted and para-substituted benzenes. However, until recent discoveries, analogous three-dimensional ortho-substituted and meta-substituted biososteres have remained underexplored, owing to their ring strain and increased s-character hybridization. This Review summarizes the emerging synthetic methodologies to access such saturated motifs and their impact on the application of bioisosteres for ortho-substituted, meta-substituted and multi-substituted benzene rings. It concludes with a perspective on the development of next-generation bioisosteres, including those within novel chemical space.

Densities, Viscosities, and Self-Diffusion Coefficients of Octan-1-ol and Related Ether-Alcohols.

Density, viscosity, and self-diffusion coefficients are reported for octan-1-ol and the related ether-alcohols 2-pentoxy-ethan-1-ol, 3-butoxypropan-1-ol, 4-propoxybutan-1-ol, 5-ethoxypentan-1-ol, and 6-methoxyhexan-1-ol covering temperature ranges from 298.15 to 359.15 K. These new data reveal structure-property relationships affected by the presence and the position of the ether moiety in the molecular structure of the ether-alcohols. Compared to octan-1-ol, the presence of the ether moiety causes an increase in intermolecular hydrogen bonding interactions, resulting in higher densities. The increase in density is less pronounced for those ether-octanols that engage in intramolecular hydrogen bonding. As for the effects of the ether moiety on the dynamics, these are generally faster for the ether-alcohols compared to octan-1-ol, suggesting that hydrogen bonding between ether oxygen and hydroxy hydrogen is weaker compared to hydrogen bonding between two hydroxy groups. The activation energies obtained from an Arrhenius analysis are higher for translational motion than for momentum transfer for all alcohols. There are additional finer details across the ether alcohols for these activation barriers. These differences cancel out for the mathematical product of self-diffusion coefficient and viscosity (Dη). The effect of water impurities on the studied properties was also investigated and found to lead to small increases in densities for all alcohols. Viscosities decrease for octan-1-ol and 2-pentoxyethan-1-ol but increase for the other ether-alcohols that can engage in intramolecular hydrogen bonding.

Chiral versus achiral crystal structures of 4-benzyl-1H-pyrazole and its 3,5-di-amino derivative.

The crystal structures of 4-benzyl-1H-pyrazole (C10H10N2, 1) and 3,5-di-amino-4-benzyl-1H-pyrazole (C10H12N4, 2) were measured at 150 K. Although its different conformers and atropenanti-omers easily inter-convert in solution by annular tautomerism and/or rotation of the benzyl substituent around the C(pyrazole)-C(CH2) single bond (as revealed by 1H NMR spectroscopy), 1 crystallizes in the non-centrosymmetric space group P21. Within its crystal structure, the pyrazole and phenyl aromatic moieties are organized into alternating bilayers. Both pyrazole and phenyl layers consist of aromatic rings stacked into columns in two orthogonal directions. Within the pyrazole layer, the pyrazole rings form parallel catemers by N-H⋯N hydrogen bonding. Compound 2 adopts a similar bilayer structure, albeit in the centrosymmetric space group P21/c, with pyrazole N-H protons as donors in N-H⋯π hydrogen bonds with neighboring pyrazole rings, and NH2 protons as donors in N-H⋯N hydrogen bonds with adjacent pyrazoles and other NH2 moieties. The crystal structures and supra-molecular features of 1 and 2 are contrasted with the two known structures of their analogs, 3,5-dimethyl-4-benzyl-1H-pyrazole and 3,5-diphenyl-4-benzyl-1H-pyrazole.