Class Of Compounds Research Articles

Antiaromatic 2-Azaboroles with π4σ2 Electronic Configuration.

Similar to pyridine, which is a structural analog of benzene, 2-azaborole can be viewed as a structural analog of borole, in which the CH group at the 2-position is replaced by an N atom. Due to its unique π4σ2 electronic configuration, it should exhibit Lewis acidity, antiaromaticity, as well as Lewis basicity simultaneously. However, this uniqueness also makes its synthesis and isolation particularly challenging. One anticipated issue is its readiness for self-dimerization. This work proposes 2-azaborole and targets the synthesis and characterization of its derivatives for the first time. By reacting benzoborirene C6H4{BN(SiMe3)2} with bulky nitriles, crystalline benzo-fused 2-azaboroles have been successfully achieved and fully characterized. The importance of steric hindrance has been experimentally verified, showing that insufficient kinetic protection results in the dimerization of benzo-fused 2-azaboroles to form BN-allenophanes, a class of 10-membered macrocyclic compounds featuring two BN-allene units. The unique electronic structure of 2-azaborole as well as the mechanism of dimerization has been corroborated by theoretical calculations. In addition, its ability to act both as a Lewis acid and a Lewis base is demonstrated through its reaction with 1,3-diisopropyl-4,5-dimethylimidazolin-2-ylidene (MeIiPr) and AlCl3, respectively, which also implies the potential of the 2-azaborole motif as a σ-donor ligand for main group and organometallic chemistry.

Evaluation of Echinacea purpurea Extracts as Immunostimulants: Impact on Macrophage Activation.

Echinacea purpurea has been traditionally used to strengthen the immune system. Therefore, herein, we investigated the potential of E. purpurea aqueous extracts (AEs) obtained from flowers (F), leaves (L), or roots (R) as an immune booster in human primary monocyte-derived macrophages (hMDMs). Additionally, to identify the main class of compounds (phenolic/carboxylic acids vs. alkylamides) responsible for the bioactivity, the three AEs were fractioned by semi-preparative high-performance liquid chromatography (HPLC). The AEs and the isolated phenolic/carboxylic acidic fractions were not cytotoxic for hMDMs for all tested concentrations, as confirmed by the metabolic activity and DNA content assays. Moreover, AE drastically induced the production of the interleukin (IL)-6 and tumor necrosis factor (TNF)-α, with a minimal effect on IL-1β and prostaglandin E2 (PGE2), supporting their potential for macrophage activation. Interestingly, in the presence of the phenolic/carboxylic acidic fractions, this efficacy considerably decreased, suggesting a complementary effect between compounds. AE also triggered the phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2 and p38 signaling pathways and upregulated the cyclooxygenase (COX)-2 expression in hMDMs. Overall, AE-F was demonstrated to be the most powerful immunostimulant extract that can be related to their higher number in identified bioactive compounds compared to AE-L and AE-R. These results highlight the efficiency of E. purpurea AE to enhance the function of a key cell type of the immune system and their potential as immunostimulant formulations for patients with a compromised immune system due to certain diseases (e.g., acquired immunodeficiencies) and treatments (e.g., chemotherapy).

Assessing the Potential of 1,2,3-Triazole-Dihydropyrimidinone Hybrids Against Cholinesterases: In Silico, In Vitro, and In Vivo Studies.

Combining the pharmacological properties of the 1,2,3-triazole and dihydropyrimidinone classes of compounds, two small families of mono- and di(1,2,3-triazole)-dihydropyrimidinone hybrids, A and B, were previously synthesized. The main objective of this work was to investigate the potential anti-Alzheimer effects of these hybrids. The inhibitory activities of cholinesterases (AChE and BuChE), antioxidant activity, and the inhibitory mechanism through in silico (molecular docking) and in solution (STD-NMR) experiments were evaluated. The 1,2,3-triazole-dihydropyrimidinone hybrids (A and B) showed moderate in vitro inhibitory activity on eqBuChE (IC50 values between 1 and 58.4 μM). The best inhibitor was the hybrid B4, featuring two 1,2,3-triazole cores, which exhibited stronger inhibition than galantamine, with an IC50 of 1 ± 0.1 μM for eqBuChE, through a mixed inhibition mechanism. Among the hybrids A, the most promising inhibitor was A1, exhibiting an IC50 of 12 ± 2 µM, similar to that of galantamine. Molecular docking and STD-NMR experiments revealed the key binding interactions of these promising inhibitors with BuChE. Hybrids A and B did not display Artemia salina toxicity below 100 μM.

Occurrence and profiles of bisphenol A and its analogues in marine shrimps from Tianjin and their implications for human exposure

Bisphenols, a class of compounds with endocrine-disrupting characteristics, encompassing its effects on reproduction, nervous and immune systems. Diet represents the principal route of bisphenols intake, prompting concerns about dietary exposure. In this study, the occurrence and content of nine bisphenols in 96 marine shrimps from Tianjin were detected and analysed using ultra high performance liquid chromatography mass spectrometer and solid-phase extraction. The analytical method was validated to demonstrate reliable analytical performance. The results revealed that bisphenol A was detected in the majority of the samples, with the highest detection rate among the nine bisphenols, followed by bisphenol S, while the remaining bisphenols were not detected. A discernible age-related trend was identified in the assessment of dietary exposure, whereby exposure levels increased with decreasing age. Furthermore, regional discrepancies were observed, yet no gender-based distinctions were discerned. The estimated daily intake to total bisphenols through marine shrimp in this study was lower than the current tolerable daily intake set by the European Food Safety Authority, and it can be assumed that the risk of exposure to the nine bisphenols investigated through dietary is acceptable. However, given the recently proposed draft values by the European Food Safety Authority and the higher exposures observed in children and teenagers, further surveillance and dietary guidance is required. To our knowledge, this is the first study in Tianjin to evaluate the health risks associated with bisphenol A and its analogues via marine shrimp, which can monitor dietary safety and protect population health.

Advances in the Synthesis of 3‐Acyl‐2‐Pyridones: Strategies and Methods for Accessing the Versatile Scaffold

ABSTRACTThe syntheses and bioevaluation of 3‐acyl‐2‐pyridones have garnered significant interest in recent years as a novel class of compounds with diverse biological activities. The bioactivities cover a wide range of therapeutic areas including antimicrobial, antitumor, anti‐inflammatory, antifungal, antibiotic, neuritogenic, cytotoxic, and antiviral activities. Therefore, 3‐acyl‐2‐pyridone scaffold offers a versatile platform for the development of new molecules with potential applications in medicinal chemistry. The recent exploration on synthesis and bioevaluation of 3‐acyl‐2‐pyridones has yielded promising results, making them attractive targets for further optimization and development of new therapeutic agents. This review summarizes the available information on total synthesis of 3‐acyl‐2‐pyridone containing natural products, and the other synthetic strategies developed for accessing the 3‐acyl pyridones such as multicomponent synthesis, condensation reaction, microwave‐assisted synthesis, catalytic hydrogenation reactions, metalation reaction, Michael addition, and formylation reactions. The presented information may serve as a valuable resource for researchers working in the field of medicinal chemistry and drug discovery, stimulating further exploration and development of this intriguing scaffold.

Synthesis, computational analysis, and anti-proliferative evaluation of novel bithienylbenzamidine derivatives: Towards cytostatic cancer therapeutics

Our research unveils the synthesis and characterization of four novel monocationic 2,5-diarylbithiophene derivatives 4a-d, prepared through Suzuki cross-coupling reactions and subsequent amidine formation. Density Functional Theory (DFT) calculations provide unprecedented insights into the electronic properties and structure-activity relationships of these compounds. In vitro screening against the NCI-60 cancer cell panel demonstrates remarkable anti-proliferative activities. Compound 4c emerges as a standout candidate, exhibiting potent growth inhibition across multiple cancer types, with GI50 values as low as 0.36 µM against certain ovarian cancer lines. Intriguingly, our research suggests a potential shift from purely cytotoxic towards more cytostatic behavior, potentially offering improved therapeutic windows and reduced side effects. Molecular docking studies provide evidence for the compounds' interaction with human carbonic anhydrase IX, hinting at a possible mechanism of action. This comprehensive study not only introduces a promising new class of anti-cancer compounds but also provides a rich foundation of structural, electronic, and biological data to fuel future research. The bithienylbenzamidine derivatives, particularly compound 4c, represent exciting candidates for further development in the ongoing battle against cancer.

Biological activities of metal complexes with Schiff base

Abstract Schiff bases are a class of synthetic compounds that form when primary amines combine with aldehydes or ketones. These compounds are incredibly important across various fields, such as biology, catalysis, and optics, due to their diverse features. One notable aspect is their ability to form complexes with transition metals, which opens up a wide range of potential uses, particularly in human systems. In the human body, Schiff base metal complexes display a range of biological actions, including antibacterial, antifungal, anticancer, and antimalarial properties. The versatility of Schiff bases in reacting with different transition metals gives these complexes intriguing potential for addressing biological issues and treating diseases. This article explores various examples of Schiff bases, metal complexes, and their associated ligands, highlighting their usefulness in a variety of biological applications. The potential of Schiff base metal complexes as valuable agents in resolving medical difficulties and advancing biomedical research is emphasized.

Glyoxal Caging of Nucleoside Antivirals toward Self-Activating, Extended-Release Prodrugs.

Nucleoside antivirals are a leading class of compounds prescribed as a first-line treatment for viral infections. However, inherent limitations such as low solubility and circulation lifetime can necessitate multi-intraday dosing. Here, we deploy the 1,2-dialdehyde glyoxal to generate antiviral nucleoside prodrugs with enhanced pharmacokinetic properties and extended-release activity to combat poor patient adherence. The near-quantitative reaction of glyoxal with acyclovir (ACV) drastically improves ACV solubility and enables subsequent drug release with a half-life of 1.9 h under physiological conditions. Further, glyoxal caging thermoreversibly disrupts ACV activity against HIV-1 reverse transcription in vitro and HSV-1 pathology in cellulo. Finally, the amenability of a panel of nucleoside reverse transcriptase inhibitors to glyoxal caging showcases the potential of this highly versatile method for achieving timed-release activation of a clinically important class of antiviral therapeutics.

The structural and mechanistic bases for the viral resistance to allosteric HIV-1 integrase inhibitor pirmitegravir.

Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are investigational antiretroviral agents that potently impair virion maturation by inducing hyper-multimerization of IN and inhibiting its interaction with viral genomic RNA. The pyrrolopyridine-based ALLINI pirmitegravir (PIR) has recently advanced into phase 2a clinical trials. Previous cell culture-based viral breakthrough assays identified the HIV-1(Y99H/A128T IN) variant that confers substantial resistance to this inhibitor. Here, we have elucidated the unexpected mechanism of viral resistance to PIR. Although both Tyr99 and Ala128 are positioned within the inhibitor binding V-shaped cavity at the IN catalytic core domain (CCD) dimer interface, the Y99H/A128T IN mutations did not substantially affect the direct binding of PIR to the CCD dimer or functional oligomerization of full-length IN. Instead, the drug-resistant mutations introduced a steric hindrance at the inhibitor-mediated interface between CCD and C-terminal domain (CTD) and compromised CTD binding to the CCDY99H/A128T + PIR complex. Consequently, full-length INY99H/A128T was substantially less susceptible to the PIR-induced hyper-multimerization than the WT protein, and HIV-1(Y99H/A128T IN) conferred >150-fold resistance to the inhibitor compared with the WT virus. By rationally modifying PIR, we have developed its analog EKC110, which readily induced hyper-multimerization of INY99H/A128T in vitro and was ~14-fold more potent against HIV-1(Y99H/A128T IN) than the parent inhibitor. These findings suggest a path for developing improved PIR chemotypes with a higher barrier to resistance for their potential clinical use.IMPORTANCEAntiretroviral therapies save the lives of millions of people living with HIV (PLWH). However, the evolution of multi-drug-resistant viral phenotypes is a major clinical problem, and there are limited or no treatment options for heavily treatment-experienced PLWH. Allosteric HIV-1 integrase inhibitors (ALLINIs) are a novel class of antiretroviral compounds that work by a unique mechanism of binding to the non-catalytic site on the viral protein and inducing aberrant integrase multimerization. Accordingly, ALLINIs potently inhibit both wild-type HIV-1 and all drug-resistant viral phenotypes that have so far emerged against currently used therapies. Pirmitegravir, a highly potent and safe investigational ALLINI, is currently advancing through clinical trials. Here, we have elucidated the structural and mechanistic bases behind the emergence of HIV-1 integrase mutations in infected cells that confer resistance to pirmitegravir. In turn, our findings allowed us to rationally develop an improved ALLINI with substantially enhanced potency against the pirmitegravir-resistant virus.

Validating Small-Molecule Force Fields for Macrocyclic Compounds Using NMR Data in Different Solvents.

Macrocycles are a promising class of compounds as therapeutics for difficult drug targets due to a favorable combination of properties: They often exhibit improved binding affinity compared to their linear counterparts due to their reduced conformational flexibility, while still being able to adapt to environments of different polarity. To assist in the rational design of macrocyclic drugs, there is need for computational methods that can accurately predict conformational ensembles of macrocycles in different environments. Molecular dynamics (MD) simulations remain one of the most accurate methods to predict ensembles quantitatively, although the accuracy is governed by the underlying force field. In this work, we benchmark four different force fields for their application to macrocycles by performing replica exchange with solute tempering (REST2) simulations of 11 macrocyclic compounds and comparing the obtained conformational ensembles to nuclear Overhauser effect (NOE) upper distance bounds from NMR experiments. Especially, the modern force fields OpenFF 2.0 and XFF yield good results, outperforming force fields like GAFF2 and OPLS/AA. We conclude that REST2 in combination with modern force fields can often produce accurate ensembles of macrocyclic compounds. However, we also highlight examples for which all examined force fields fail to produce ensembles that fulfill the experimental constraints.

Assessing the impact of packaging materials on anoxic biotrickling filtration of siloxanes in biogas: Effectiveness of activated carbon in removal performance

Siloxanes (VMS) represent a class of organosilicon compounds known for their adverse effects on both the environment and human health. Their presence in biogas significantly hinders its economic valorisation, highlighting the need for effective treatment methods. This study investigates the performance of three different packing materials in the anoxic biofiltration of VMS (L2, L3, D4 and D5). The materials evaluated included plastic rings (BTF-1), polyurethane foam (BTF-2) and plastic rings combined with activated carbon (80:20) (BTF-3). Among them, BTF-3 exhibited superior performance, achieving maximum VMS removal efficiencies (REs) of 90%, including the complete elimination of L3 and D4, and ∼80% removal of D5, attributed to the presence of activated carbon. However, the abatement of L2 was inferior to that of other VMS (<80%), which was attributed to the activated carbon's affinity for larger molecular weights and critical diameters. In contrast, BTF-1 and BTF-2 supported maximum VMS removals of 40%. Notably, neither increasing the trickling liquid velocity from 2 to 4.5 m h⁻1 nor adding Fe-carbon nanoparticles to the solution had any impact on the BTFs' performance. Following the successful results observed in BTF-3, gas residence time was reduced from 60 to 42 min, consequently leading to an increase in the EC from 366 to 509 mg m−3 h−1 (corresponding to an RE = 87%). Despite the different performance of the BTFs, comparable bacterial communities were identified, dominated by the genera Thermomonas, Corynebacterium, Aquimonas, Thauera and Parvibaculum. The results obtained in this study highlighted the potential of activated carbon as packing material for enhancing abatement performance during biotrickling filtration and identified new bacterial genera with potential for VMS degradation.

THE GREEN APPROACH FOR THE SYNTHESIS OF SOME HYDROQUINOLINE DERIVATIVES COMPOUND VIA HANTZSCH REACTION

Since that hydroquinoline and acridine compounds serve as the fundamental building blocks for the synthesis of many different pharmaceuticals, they are among the most significant classes of chemical compounds that attract the interest of numerous researchers and pharmacologists. Therefore, in this research, The Hantzch reaction was used to prepare these types hydroquinoline and acridine derivatives of compounds, through the reaction of a number substituted benzaldehyde with demidone and α-β diketone substitutes by refluxed with sodium acetate in the presence of iodine and a 1-sulfo-4-(3-(Ferricoxide-Silicondioxide nanopowdertrioxisilyl)propyl) piperazinum-1,4-diphosphate as a catalyst to form 7,7- dimethyl -4,6,7,8-tetrahydroquinoline derivatives which is represented by compounds (1-12) or in the same way by react benzaldehyde substitutes react with demidone and 4-isopropyl cyclohexanone 1-one to form acridin derivatives represented by compounds (13 -17). All product compound are characterized using 1H-NMR spectra and the results confirmed the structures.

Photocleavable Protecting Groups Using a Sulfite Self‐Immolative Linker for High Uncaging Quantum Yield and Aqueous Solubility

AbstractUsing light as an external stimulus to control (bio)chemical processes offers many distinct advantages. Most importantly, it allows for spatiotemporal control simply through operating the light source. Photocleavable protecting groups (PPGs) are a cornerstone class of compounds that are used to achieve photocontrol over (bio)chemical processes. PPGs are able to release a payload of interest upon light irradiation. The successful application of PPGs hinges on their efficiency of payload release, captured in the uncaging Quantum Yield (QY). Heterolytic PPGs efficiently release low pKa payloads, but their efficiency drops significantly for payloads with higher pKa values, such as alcohols. For this reason, alcohols are usually attached to PPGs via a carbonate linker. The self‐immolative nature of the carbonate linker results in concurrent release of CO2 with the alcohol payload upon irradiation. We introduce herein novel PPGs containing sulfites as self‐immolative linkers for photocaged alcohol payloads, for which we discovered that the release of the alcohol proceeds with higher uncaging QY than an identical payload released from a carbonate‐linked PPG. Furthermore, we demonstrate that uncaging of the sulfite‐linked PPGs results in the release of SO2 and show that the sulfite linker improves water solubility as compared to the carbonate‐based systems.

Mechanism-Based Allylic Carbasugar Chlorides That Form Covalent Intermediates with α- and β-Galactosidases.

Glycoside hydrolases have been implicated in a wide range of human conditions including lysosomal storage diseases. Consequently, many researchers have directed their efforts towards identifying new classes of glycoside hydrolase inhibitors, both synthetic and from natural sources. A large percentage of such inhibitors are reversible competitive inhibitors that bind in the active site often due to them possessing structural features, often a protonatable basic nitrogen atom, that mimic the enzymatic transition state. We report that mechanism-based small molecule galacto-like configured cyclohexenyl carbasugars form reversible covalent complexes with both α-galactosidase and β-galactosidase. In addition, we show that the β-galactosidase from Aspergillus oryzae reacts with three different carbasugar inhibitors, with three different second-order rate constants (kinact/Ki), to give the same enzyme-carbasugar covalent intermediate. The surprising observation that the α-galacto-configured inhibitor covalently labels the A. oryzae β-galactosidase highlights the catalytic versatility of glycoside hydrolases. We expect that cyclohexenyl covalent inhibitors will become an important class of compounds in the chemical biologist's tool box.

Photocleavable Protecting Groups Using a Sulfite Self-Immolative Linker for High Uncaging Quantum Yield and Aqueous Solubility.

Using light as an external stimulus to control (bio)chemical processes offers many distinct advantages. Most importantly, it allows for spatiotemporal control simply through operating the light source. Photocleavable protecting groups (PPGs) are a cornerstone class of compounds that are used to achieve photocontrol over (bio)chemical processes. PPGs are able to release a payload of interest upon light irradiation. The successful application of PPGs hinges on their efficiency of payload release, captured in the uncaging Quantum Yield (QY). Heterolytic PPGs efficiently release low pKa payloads, but their efficiency drops significantly for payloads with higher pKa values, such as alcohols. For this reason, alcohols are usually attached to PPGs via a carbonate linker. The self-immolative nature of the carbonate linker results in concurrent release of CO2 with the alcohol payload upon irradiation. We introduce herein novel PPGs containing sulfites as self-immolative linkers for photocaged alcohol payloads, for which we discovered that the release of the alcohol proceeds with higher uncaging QY than an identical payload released from a carbonate-linked PPG. Furthermore, we demonstrate that uncaging of the sulfite-linked PPGs results in the release of SO2 and show that the sulfite linker improves water solubility as compared to the carbonate-based systems.

A New Technique Using Multicomponent Reactions of Isatins to Synthesize Pyrroloimidazole Derivatives

A multicomponent technique was utilized to synthesize pyrroloimidazoles, a novel class of compounds, with exceptional efficiency. The reaction involved the combination of oxoindolinylidene malononitrile, ethyl 2-arylamino-4-dioxo-4-arylbutanoates, hydrazonoyl chlorides, ammonium acetate, and ethyl bromopyruvate in an aqueous solution at room temperature. The presence of Ag/Fe3O4@MWCNTs MNCs intensified the reaction. This study examines the antioxidant properties of pyrroloimidazoles, in addition to other investigations undertaken within the same study. The manufacture of pyrroloimidazole exhibited several advantageous characteristics, such as rapid reactions, elevated yields of the end product, and straightforward separation of the catalyst and product from the reaction mixture.

Exploring nitro-Tröger’s bases for ct-DNA and HSA sensing: An experimental and theoretical study

In this study, we present Tröger’s base analogs synthesized through condensation between p-formaldehyde and methyl-nitro-anilines in good yields. Tröger’s bases exhibit absorption peaks around 350 nm attributed to allowed ππ* electronic transitions. The fluorescence emission at 380 nm showed no correlation with the position of the nitro group. Spectroscopic analyses employing UV–Vis absorption, steady-state fluorescence emission, and molecular docking calculations revealed that these Tröger’s bases interact effectively with ct-DNA and human serum albumin (HSA). These findings suggest that this class of compounds might serve as promising optical sensors for biomacromolecules.

Comprehensive Evaluation of Quality and Differences in Silene viscidula Franch from Different Origins Based on UPLC-ZENO-Q-TOF-MS/MS Compounds Analysis and Antioxidant Capacity.

Silene viscidula Franch is mainly produced in southwest China. The region has a vast area and rich climate, which has an impact on the quality of the plants due to the differences in distribution between the origins. There is a lack of systematic research on its chemical compounds in the existing literature, and fewer studies have been reported for the active compounds of this plant. Therefore, high-resolution liquid mass spectrometry was used in this study. Sixty batches of Silene viscidula Franch samples from twenty origins in three provinces were analyzed for compounds. A database of chemical compounds of Silene viscidula Franch was established through node-to-node information in the GNPS molecular network, as well as literature records. The ion fragmentation information obtained was compared with the literature data and analyzed and identified by importing the mass spectrometry software PeakView 1.2. Then, the MarkerView t-test was applied to analyze and identify the compounds of Silene viscidula Franch from different origins. Afterwards, the antioxidant activity of Silene viscidula Franch from different origins was preliminarily evaluated using DPPH and ABTS free radical scavenging assays. The results showed a total of 78 compounds, including 34 steroids, 14 triterpenoid saponins, 30 flavonoid glycosides, and other classes of compounds, such as alkaloids. The cleavage patterns of steroids, triterpenoid saponins, and flavonoids in positive-ion mode were also summarized. Based on the p-value of the t-test (p < 0.05), 29 differential compounds were screened out. The relative contents of saponins and steroidal compounds in these samples were found to be associated with antioxidant activity. This study provided a preliminary reference for the establishment of a comprehensive evaluation system for the quality of Silene viscidula Franch.

Accumulation and depuration of 4,5-dihydro-KmTx2 from Karlodinium veneficum in the bivalves, Mercenaria mercenaria and Sinonovacula constricta

Bivalves (e.g., clams, oysters, mussels, scallops) are a significant part of the global diet and are harvested for their nutritional value, but as filter feeders they are susceptible to the accumulation of toxins produced by certain species of phytoplankton. Karlotoxins (KmTxs) are a class of amphidinol-like compounds with hemolytic, ichthyotoxic, and cytotoxic properties that have been associated with harmful algal blooms, and the dinoflagellate Karlodinium veneficum uses KmTxs to facilitate prey capture and deter grazing by other organisms. In this work, we examined the accumulation and depuration of 4,5-dihydro-KmTx2, a karlotoxin previously isolated from K. veneficum, in two bivalves with different life habits, i.e., Sinonovacula constricta Lamarck and Mercenaria mercenaria Linnaeus. After both bivalves received K. veneficum GM5 in their feed for a long period of 10 days, 4,5-dihydro-KmTx2 was accumulated considerably in the visceral mass, but there was almost no toxin accumulation in the muscle. The accumulation was more severe for M. mercenaria than S. constricta. The toxin was cleared almost completely from the bivalves 5 days after K. veneficum GM5 was removed from the feed. For both bivalves, the bait microalgae I. galbana slowed both the accumulation and the depuration of the toxin.

X-ray Structure of Eleven New N,N′-Substituted Guanidines: Effect of Substituents on Tautomer Structure in the Solid State

Guanidine-containing molecules are an interesting class of compounds within both medicinal and material sciences. Having knowledge of their tautomerism is key in designing guanidines that interact with biological and chemical receptors. However, there are limited data on the solid-phase structure of N,N′-substituted guanidines. Thus, eleven guanidines bearing a 4,6-dimethylpyrimidyl at one end and substituents of varying sizes and electronic properties at the other side, were synthesised, crystallised, and analysed by X-ray crystallography. Calculations of isolated molecules of tautomer energies and bond lengths were performed for comparison. One class of guanidines crystallised as a cis–trans tautomer with the shorter bond directed towards the pyrimidyl unit. When more electron-deficient aniline substituents were inserted, the crystallised tautomer changed to a cis–cis form where the shorter bond was directed towards the aniline. The switch in the tautomer structure is concluded to be due to both the electronic properties of the substituents and the intermolecular hydrogen bonding in the crystal lattice.