Hydrogen Bond Acceptor Groups Research Articles

Unraveling the Role of Deep Eutectic Solvents with Varying Hydrogen-Bond Acceptors on the Thermoresponsive Polymer Poly(N-isopropylacrylamide).

Deep eutectic solvents (DESs) have emerged as promising tools for crafting polymeric materials across diverse domains. This study delves into the impact of a series of DESs on the phase behavior of poly(N-isopropylacrylamide) (PNIPAM) in aqueous environments, presenting compelling insights into their performance. Specifically, we explore the conformational phase behavior of PNIPAM in the presence of four distinct lactic acid (LA)-based DESs: LA-betaine (LA-BET), LA-proline (LA-PRO), LA-choline chloride (LA-CC), and LA-urea (LA-U). By maintaining a consistent hydrogen-bond donor (HBD) while varying the hydrogen-bond acceptor (HBA), we unravel how different DES compositions modulate the phase transition behavior of PNIPAM. Our findings underscore the profound influence of DESs comprising LA as the HBD and diverse HBAs-BET, PRO, CC, and U on the thermoresponsive behavior of PNIPAM. Employing spectroscopic techniques such as ultraviolet-visible (UV-vis) spectroscopy, steady-state fluorescence, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), ζ-potential, and transmission electron microscopy (TEM), we elucidate the preferential interactions between the HBA groups within DESs and the hydration layer of PNIPAM. Notably, temperature-dependent DLS analyses reveal a discernible decrease in the lower critical solution temperature (LCST) of PNIPAM with increasing DES concentration, ultimately disrupting the hydrogen-bond interactions and resulting in early hydrophobic collapse of the polymer, which can be clearly seen in the TEM micrographs. Furthermore, the formation of polymer composites within the mixed system leads to notable alterations in the physiochemical properties of PNIPAM, as evidenced by shifts in its LCST value in the presence of DESs. This perturbation disrupts hydrogen-bond interactions, inducing hydrophobic collapse of the polymers, a phenomenon vividly captured in TEM micrographs. In essence, our study sheds new light on the pivotal role of varying HBA groups within DESs in modulating the conformational transitions of PNIPAM. These insights not only enrich our fundamental understanding but also hold immense promise for the development of smart polymeric systems with multifaceted applications spanning bioimaging, biomedical science, polymer science, and beyond.

A perspective on cellulose dissolution with deep eutectic solvents

Currently, membrane manufacturing relies heavily on fossil-based solvents and polymers, resulting in significant negative impacts on human health and the environment. Thus, there is an urgent need for eco-friendly, low-toxicity, and sustainable solvents and polymers to comply with the United Nations’ sustainable development goals. Cellulose, as a green, natural, and abundant polymer, offers a sustainable source for membrane manufacturing. However, a significant challenge exists in dissolving cellulose due to strong intermolecular and intramolecular hydrogen bonds within cellulose molecules. Deep eutectic solvents (DESs), which contain both hydrogen bond donor and acceptor groups, have received significant attention as alternative solvents for cellulose dissolution owing to their low cost, low toxicity, environmentally friendly nature, ease of synthesis, and versatility. This review examines experimental studies, and theoretical approaches, highlighting key findings and factors influencing cellulose dissolution in deep eutectic solvents.

An Atomic-Level Perspective on the interactions between Organic Pollutants and PET particles: A Comprehensive Computational Investigation.

Microplastics (MPs) have recently attracted a lot of attention worldwide due to their abundance and potentially harmful effects on the environment and on human health. One of the factors of concern is their ability to adsorb and disperse other harmful organic pollutants in the environment. To properly assess the adsorption capacity of MP for organic pollutants in different environments, it is pivotal to understand the mechanisms of their interactions in detail at the atomic level. In this work, we studied interactions between polyethylene terephthalate (PET) MP and small organic pollutants containing different functional groups within the framework of density functional theory (DFT). Our computational outcomes show that organic pollutants mainly bind to the surface of a PET model via weak non-bonding interactions, mostly hydrogen bonds. The binding strength between pollutant molecules and PET particles strongly depends on the adsorption site while we have found that the particle size is of lesser importance. Specifically, carboxylic sites are able to form strong hydrogen bonds with pollutants containing hydrogen bond donor or acceptor groups. On the other hand, it is found that in such kind of systems π-π interactions play a minor role in adsorption on PET particles.

Exploring the Transmembrane Behaviors of Dietary Flavonoids under Intestinal Digestive Products of Different Lipids: Insights into the Structure-Activity Relationship In Vitro.

This study aimed to investigate the transmembrane transport behavior and structure-activity relationships of various dietary flavonoids in the presence of dietary lipids derived from different sources in vitro. Results revealed that the digestion products of soybean oil (SOED) and lard (LOED) augmented the apparent permeability coefficients of most dietary flavonoids, and SOED exhibited higher transport compared with LOED. The structural properties of flavonoids and the potential interactions between fatty acids in these digestion products and flavonoids may influence the outcomes. 3D quantitative structure-activity relationship analyses revealed that incorporating small-volume groups at position 8 of the A-ring augmented the transmembrane transfer of flavonoids in the LOED system compared with the control group. By contrast, the integration of hydrophobic groups at position 5 of the A-ring and hydrogen bonding acceptor groups at position 6 of the A-ring enhanced the transmembrane transportation of flavonoids in the SOED system. Molecular dynamics simulations revealed that the SOED system may facilitate the interactions with flavonoids to form more stable and compact fatty acid-flavonoid complexes compared to the LOED system. These findings may provide valuable insights into flavonoid absorption to facilitate the development and utilization of functional foods or dietary supplements based on dietary flavonoids.

Transmembrane behaviors and quantitative structure–activity relationship of dietary flavonoids in the presence of intestinal digestive products from different carbohydrate sources based on in vitro and in silico analysis

Bioavailability plays a key role for flavonoids to exert their bioactivities. This study investigated the transmembrane transport behavior and structure–activity of dietary flavonoids. Results showed that the apparent permeability coefficients of some flavonoids could be significantly increased when digestion products from rice flour (RD) or wheat flour (WD) are present (p < 0.05), especially in the WD, potentially due to higher reducing sugar (p < 0.05). 3D-QSAR revealed that the hydrogen bond acceptor groups at positions 5 and 6 of ring A, small-volume groups at position 3′, hydrophobic groups at position 4′, and large-volume groups at position 5′ of ring B increased the transmembrane transport of flavonoids in the WD. A hydrogen bond donor group at position 4′ of ring B enhanced the transmembrane transport of flavonoid compounds in the RD. These findings contribute to our comprehensive understanding of flavonoid absorption within the context of intestinal carbohydrate digestion.

Hydration of Propargyl Esters Catalyzed by Gold(I) Complexes with Phosphoramidite Calix[4]pyrrole Cavitands as Ligands.

We report the synthesis and characterization of two diastereomeric phosphoramidite calix[4]pyrrole cavitands and their corresponding gold(I) complexes, 2in•Au(I)•Cl and 2out•Au(I)•Cl, featuring the metal center directed inward and outward with respect to their aromatic cavity. We studied the catalytic activity of the complexes in the hydration of a series of propargyl esters as the benchmarking reaction. All substrates were equipped with a six-membered ring substituent either lacking or including a polar group featuring different hydrogen bond acceptor (HBA) capabilities. We designed the substrates with the polar group to form 1:1 inclusion complexes of different stabilities with the catalysts. In the case of 2in•Au(I)•OTf, the 1:1 complex placed the alkynyl group of the bound substrate close to the metal center. We compared the obtained results with those of a model phosphoramidite gold(I) complex lacking a calix[4]pyrrole cavity. We found that for all catalysts, the presence of an increasingly polar HBA group in the substrate provoked a decrease in the hydration rate constants. We attributed this result to the competing coordination of the HBA group of the substrate for the Au(I) metal center of the catalysts.

Synthetic Biology Pathway to Nucleoside Triphosphates for Expanded Genetic Alphabets.

One horizon in synthetic biology seeks alternative forms of DNA that store, transcribe, and support the evolution of biological information. Here, hydrogen bond donor and acceptor groups are rearranged within a Watson-Crick geometry to get 12 nucleotides that form 6 independently replicating pairs. Such artificially expanded genetic information systems (AEGIS) support Darwinian evolution in vitro. To move AEGIS into living cells, metabolic pathways are next required to make AEGIS triphosphates economically from their nucleosides, eliminating the need to feed these expensive compounds in growth media. We report that "polyphosphate kinases" can be recruited for such pathways, working with natural diphosphate kinases and engineered nucleoside kinases. This pathway in vitro makes AEGIS triphosphates, including third-generation triphosphates having improved ability to survive in living bacterial cells. In α-32P-labeled forms, produced here for the first time, they were used to study DNA polymerases, finding cases where third-generation AEGIS triphosphates perform better with natural enzymes than second-generation AEGIS triphosphates.

Mechanistic Insight of Polymer Effects on the Kinetic of Solution-Mediated Phase Transformation of Nitrofurantoin Anhydrate to Monohydrate.

Nitrofurantoin is an effective antibacterial drug for the treatment of lower urinary tract infection. However, the anhydrate form can easily transform to the less soluble hydrate form (monohydrate) during dissolution, resulting in a reduction of dissolution rate and oral bioavailability. Therefore, inhibition of phase transformation is vital to stabilize the quality of drugs. In this work, the potential of polyethylene glycol (PEG 8000), polyvinyl pyrrolidone (PVP K30), poloxamer 188 and hydroxypropyl methylcellulose (HPMC) to inhibit the hydration of nitrofurantoin during dissolution was investigated by experimental and simulation approaches. The rates of phase transformation were decreased in the presence of PEG 8000 and poloxamer 188, and PVP K30 and HPMC completely inhibited the phase transformation of anhydrate. The abundant hydrogen bond donor and acceptor groups of PVP and HPMC may easily establish intermolecular interactions with nitrofurantoin molecules, accounting for stronger inhibition of nucleation. Besides, the molecular dynamic simulation further indicated the formation of more extensive interactions between PVP K30 (or HPMC) and the (111) face of monohydrate, suggesting that the strong absorption of polymers on the surface and thus block the sites for incorporation of new growth. This study provides a mechanistic insight into the inhibition of nitrofurantoin hydration by polymeric additives, which helps design formulations and improve the physical stability of anhydrate.

A New ent-kaurene Diterpenoid Isolated from Leaves of Espeletia semiglobulata Cuatrec. and its Potential Antimicrobial Activity

The fraction of the neutral extraction of the leaves of Espeletia semiglobulata Cuatrec. was subjected to chromatographic separation, it yielded four ent-kaurene type diterpenoids: three known [ent-kaur-16-en-19-al (I), ent-kaur-18-nor-16-en-4-ol (III), ent-kaur-16-en-19-ol (IV)] and a new one elucidated as ent-kaur-3-acetoxy-15-ene (II), based on the physicochemical and spectroscopic data of FTIR, GC-MS, and 1D and 2D NMR. These compounds were subjected to antimicrobial bioassay studies. This new ent-kaurene showed a significant inhibition potential against the growth of gram negative bacterial strains [Escherichia coli (ATCC 25922): 8 mm, Klebsiella pneumoniae (ATCC 23357): 10 mm, Pseudomonas aeruginosa (ATCC 27853): 8 mm], it also showed inhibition against the growth of fungal strain (Candida krusei: 8 mm), at a 2 mg/mL concentration. The compounds (I), (III) and (IV) failed to show any significant results in the antimicrobial screening against five bacterial strains [Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Klebsiella pneumoniae (ATCC 23357), Escherichia coli (ATCC 25922) y Pseudomonas aeruginosa (ATCC 27853)] and one fungal strain [Candida krusei (ATCC 6558)]. These results reveal a remarkable natural structure-activity relationship of the ent-kaurene core regarding the C-3 position (A ring of perhydrophenanthrene unit), whose oxygenation or addition of a hydrogen bond acceptor or donor group, improves the antimicrobial activity.

Synthesis of Degradable Polysulfamides via Sulfur(VI) Fluoride Exchange Click Polymerization of AB-Type Monomers.

Polysulfamides are the -SO2- analogues of polyureas and form an intriguing family of polymers containing hydrogen-bond donor and acceptor groups. However, unlike polyureas, their physical properties are mostly unknown because of the scarcity of synthetic methods to access such polymers. Herein, we report an expedient synthesis of AB monomers for the synthesis of polysulfamides via Sulfur(VI) Fluoride Exchange (SuFEx) click polymerization. Upon optimization of the step-growth process, a variety of polysulfamides were isolated and characterized. The versatility of the SuFEx polymerization allowed structural modulation of the main chain through the incorporation of aliphatic or aromatic amines. While all synthesized polymers presented high thermal stability via thermogravimetric analysis, the glass-transition temperature and crystallinity were shown to be highly tied to the structure of the backbone between repeating sulfamide units through differential scanning calorimetry and powder X-ray diffraction. Careful analysis via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and X-ray crystallography also revealed the formation of macrocyclic oligomers during the polymerization of one AB monomer. Finally, two protocols were developed to efficiently degrade all synthesized polysulfamides through either chemical recycling for polymers derived from aromatic amines or oxidative upcycling for those based on aliphatic amines.

Brief insight into the in silico properties, structure–activity relationships and biotransformation of fruquintinib, an anticancer drug of a new generation containing a privileged benzofuran scaffold

Current trends in drug design notably consider so-called privileged scaffolds as the core structural fragments with decisive impact on affinity to properly chosen biological targets, potency, selectivity and toxicological characteristics of drugs and prospective drug candidates. Fruquintinib (1) is a novel synthetic selective inhibitor of vascular endothelial growth factor receptor (VEGFR) isoforms, i.e., VEGFR-1, VEGFR-2 and VEGFR-3. The therapeutic agent (1) consists of a flat bicyclic heteroaromatic ring, in which two nitrogens are suitablyincorporated, a core bicyclic heteroaromatic ring – privileged (substituted) benzofuran scaffold, and a pair of hydrogen bond (H-bond) donor and acceptor group, i.e., amide functional moiety. Fruquintinib (1) was first approved in China for the treatment of metastatic colorectal cancer, a severe malignant disease with a high mortality rate. The review article offered a brief insight into the topic of privileged structures, their drug- -like ranges of several parameters, pharmacodynamic characteristics of fruquintinib (1) and various in silico descriptors characterizing drug’s structural and physicochemical properties (molecular weight, number of heavy atoms, number of aromatic heavy atoms, fraction of sp3 C-atoms, number of H-bond acceptors, number of H-bond donors, total polar surface area, molar refractivity, molecular volume as well as parameters of lipophilicity and solubility). Some of these descriptors were related to pharmacokinetics and distribution of fruquintinib (1), and, in addition, might help predict its ability to cross passively the blood–brain barrier (BBB). Moreover, a possible connection between the induction potential on cytochrome P450 isoenzymes (CYP1A2 and CYP3A4) and passive transport of a given drug into the central nervous system via BBB was investigated. Current clinical experience and future directions regarding of fruquintinib (1) were also briefly outlined.

Identification of novel pyrazole containing ɑ-glucosidase inhibitors: insight into pharmacophore, 3D-QSAR, virtual screening, and molecular dynamics study

Pharmacophore modelling, 3 D QSAR modelling, virtual screening, and molecular dynamics study, all-in-one combination were employed successfully design and develop an alpha-glucosidase inhibitor. To explain the structural prerequisites of biologically active components, 3 D-QSAR models were generated using the selected best hypothesis (AARRR) for compounds 55 included in the model C. The selection of 3 D-QSAR models showed that the Gaussian steric characteristic is crucial to alpha glucosidase’s inhibitory potential. The alpha-glucosidase inhibitory potency of the compound is enhanced by other components, including Gaussian hydrophobic groups, Gaussian hydrogen bond acceptor or donor groups, Gaussian electrostatic characteristics, and a Gaussian steric feature. An identification of structure-activity relationships can be obtained from the developed 3 D-QSAR, C model, with R2 = 0.77 and SD = 0.02 for training set, and Q2 = 0.66, RMSE 0.02, and Pearson R = 0.81 for testing set, corresponding to elevated predictive ability. Additionally, docking and MM/GBSA experiments on 1146023 showed that it interacts with critical amino acids in the binding site when coupled with acarbose. Further, five compounds that display a high affinity for alpha-glucosidase were found, and these compounds may serve as potent leads for alpha-glucosidase inhibitor development. Biological activity will be tested for these compounds in the future. Communicated by Ramaswamy H. Sarma

Classification analysis of fatty acid synthase inhibitors using multialgorithms on topological descriptors and structural fingerprints.

Fatty acid synthase (FASN) is one of the enzymes required for fatty acid biosynthesis and is expressed as low or absent in most normal cells/tissues. However, this enzyme is upregulated in various cancer cells; hence, it can act as an important target to design and develop novel FASN inhibitors for cancer therapy. In the present investigation, a series of structurally diverse compounds that possessed FASN inhibitory activities were subjected to classification analysis using different algorithms such as support vector machine, decision tree, Naïve Bayes and random forest. The physicochemical descriptors and MACCS fingerprints were calculated using PaDEL software, and the WEKA software was utilized for the classification model building. The statistical parameters/confusion matrix calculated from the analysis revealed that the selected models have significant predictive performances. The results showed that the topological properties of the molecules are the main determinant for the activity classification. The key descriptors comprised of hydrogen bonding groups, especially acceptor (nHBAcc, minHBint9, minHBint5 and nwHBa), charge on the topological surface of the molecules (JGI10 & GGI2), ionization potential (GATS5i and GATS1i) and branching and distance between the groups (ETA_Eta_B_RC) are significantly contributed in the classification models. Further, the presence of heteroatoms (MACCSFP82, MACCSFP93 and MACCSFP131), especially nitrogen atom(s) and hydrogen bond acceptor groups (N-N group, NC(=O)N, N-C(=O)), actively contributed to the inhibitory activities. The results concluded that the topological polar properties concentrated in a specific region have significant FASN inhibitory activity. Hence, these results shall be used to develop novel molecules with increased FASN inhibitory activity.

Highly stretchable, self-healing, and adhesive polymeric eutectogel enabled by hydrogen-bond networks for wearable strain sensor

Compared with traditional hydrogels and ionic liquid gels, ionic conducting eutectogels have the advantages of temperature resistance, low cost, and biocompatibility, showing great potential in wearable stress pressure sensors and bioelectrodes. However, current eutectogels prepared from cross-linked polymers suffer from poor self-healing properties and insufficient surface-adaptive adhesion. In this work, we highlight for the first time the potential of monomers containing hydrogen-bond acceptor groups, and the obtained polymer can form hydrogen-bonding networks with deep eutectic solvents (DESs), thus endowing the eutectogel with self-healing and adhesive properties. These polymeric eutectogels were produced through polymerizing 1-vinylimidazole in emerging DES. The resultant eutectogels exhibited super-stretchability (approximately 2300% elongation), self-healing ability, and adhesion. Due to the unique properties of deep eutectic solvents, these eutectogels also exhibited high ionic conductivity and antifreeze/anti-drying properties. In addition, these properties lead to the successful realization of the eutectogels in conformal strain sensors to accurately detect human motion under a wide temperature range (−30 to 60 °C). The findings of this work would provide a promising strategy for the design of functionally integrated soft materials.

Synthesis, antimicrobial activity and 3D-QSAR study of novel 5-substituted-1,3,4-thiadiazole Schiff base derivatives

In this study, 21 new thiadiazole Schiff base derivatives were synthesized based on the reactive group splicing principle, and the structures of the target compounds were confirmed and characterized by 1H NMR, FT-IR and HRMS. The inhibition activity of the compounds was tested in vitro against Escherichia coli, Staphylococcus aureus, Aspergillus niger, Rhizopus, Penicillium, Botrytis cinerea and Alternaria using mycelial growth rate method. The results showed that most of the compounds exhibited good biological activity at a dose of 50 µg/mL. Among them, compounds 2b, 2r, and 2a exhibited inhibition rates against the tested microbe comparable to that of the control drug Chlorothalonil. A preliminary three-dimensional quantitative conformational relationship (3D-QSAR) study of the inhibitory activity of the target compounds against Aspergillus niger was carried out using CoMFA and CoMSIA, and the model results showed that increasing the volume of the 2- and 6-positions of benzene ring A and the 3-position substituent of benzene ring B, decreasing the volume of the 5-position substituent benzene ring A; increasing hydrophobic groups at the 6-position of benzene ring A and the 2′-position of benzene ring B; increasing the 3′-position hydrogen bond donor group and decreasing the 3′-position hydrogen bond acceptor group of benzene ring B can improve the biological activity of the compounds. The inhibitory activity of the compounds can be improved.

Assessment of arsenic in water, rice and honey samples using new and green vortex-assisted liquid phase microextraction procedure based on deep eutectic solvent: Multivariate study

The aim of present study was to determine the arsenic in water, honey and rice samples using a new and green vortex-assisted liquid phase microextraction (VA-LPME), which is based on deep eutectic solvent (DES) by hydride generation-atomic absorption spectrometry. Ethylenediamine-N,N'-disuccinic acid (EDDS) was used as chelating reagent for As(III) ions. Four different DES was prepared by using different combination and molar ratios of hydrogen bond donor (HBD) as benzyltriphenylphosphonium chloride, tetra-n-butylammonium bromide, choline chloride and hydrogen bond acceptor (HBA) groups as ethylene glycol, glycerol and diethanolamine. Different parameters such as pH, chelating agent amount, DES types, molar ratio and its volume, emulsifier agents and its volume, vortex time and sample volume were optimized. The accuracy of the method was confirmed with certified reference materials. The DES-VA-LPME method was validated by using linearity r2 0.9985, working range 20–600 ng L−1, limit of detection 6.5 ng L−1, limit of quantitation 20 ng L−1 and enhancement factor 70. Intra and inter day relative standard deviation was found in the range of 3.6 and 4.1% and 4.2 and 4.9%, respectively. The developed procedure was successfully utilized for determination of arsenic in water, honey and rice samples. The factorial design was used to investigate the individual and combined effects of variables as well significant and insignificant effects.

Liquefying Flavonoids with Terpenoids through Deep Eutectic Solvent Formation.

The formation of deep eutectic solvents (DES) is tied to negative deviations to ideality caused by the establishment of stronger interactions in the mixture than in the pure DES precursors. This work tested thymol and menthol as hydrogen bond donors when combined with different flavonoids. Negative deviations from ideality were observed upon mixing thymol with either flavone or flavanone, two parent flavonoids that only have hydrogen bond acceptor (HBA) groups, thus forming non-ionic DES (Type V). On the other hand, the menthol systems with the same compounds generally showed positive deviations from ideality. That was also the case with the mixtures containing the more complex hydroxylated flavonoid, hesperetin, which resulted in positive deviations when mixed with either thymol or menthol. COSMO-RS successfully predicted the behavior of the solid-liquid phase diagram of the studied systems, allowing for evaluation of the impact of the different contributions to the intermolecular interactions, and proving to be a good tool for the design of DES.

New Complexes of organotin(IV) and organosilicon(IV) with 2-{(3,4-dimethoxybenzylidene)amino}-benzenethiol: Synthesis, spectral, theoretical, antibacterial, docking studies

New series of dimethyl-, dibutyltin(IV), trimethylsilicon(IV), and phenylsilicon(IV) compounds with bidentate nitrogen and sulphur donor ligands have been synthesized with the 2-{(3,4-dimethoxybenzylidene)amino}-benzenethiol (LH), in molar ratios of 1:1 and 1:2. For structure elucidation, all produced compounds were characterized using IR, UV–vis, elemental analysis, conductance measurements, NMR (1H, 13C, 29Si, 119Sn) spectroscopy techniques. The 2-{(3,4-dimethoxybenzylidene)amino}-benzenethiol behaves as monofunctional bidentates, interacting with the tin and silicon atom via the thiolic-sulphur and azomethine-nitrogen atoms. Compound 1, 3, and 5 have a five-coordinated trigonal bipyramidal geometry surrounding the metal atoms, whereas Compound 2, 4, and 6 have deformed octahedral structures. The optimum geometrical parameters, including bond length, bond angles, HOMO, LUMO, electrophilicity index, chemical hardness, global softness, and mulliken atomic charges, were determined using density functional theory-based methods (DFT). The studied compounds and their ligands were simultaneously evaluated for antibacterial activity in-vitro and compared to streptomycin. The binding affinity of compound with bulky group and hydrogen bond acceptor groups is more in comparision of other compounds. The structure activity relationship revealed that compounds with bulky and hydrogen bond acceptor group will enhance the antibacterial activity agaisnt Staphylococcus aureus.

A fragment-based structural analysis of MMP-2 inhibitors in search of meaningful structural fragments

The matrix metalloproteinase family of Zn2+-dependent metalloenzymes are a group of proteases that possess the ability to degrade the extracellular matrix (ECM) and thus are involved in different biological processes. Being one of the prime members of this family, the matrix metalloproteinase-2 (MMP-2) is associated with several pathophysiological conditions including cancer, tumor progression, invasion, and metastasis. Due to its contribution toward human pathophysiology, MMP-2 is in the limelight of anticancer drug development research for more than three decades. Our study deals with a combination of classification-based modeling approaches with fragment-based data mining techniques on a large and diverse set of MMP-2 inhibitors. This has enabled the identification of important structural fragments/features of MMP-2 inhibitors essential for their potency and efficacy. Significantly, molecular properties such as AlogP, MW, hydrogen bond features, and the molecular fractional polar surface area can be utilized to discriminate the potent MMP-2 inhibitors from the lesser active/inactive ones. From this extensive study, it can be concluded that the hydroxamate and carboxylic acid groups as suitable zinc-binding groups (ZBGs) for potent MMP-2 inhibition. This study also concludes the importance of solvent accessibility, hydrogen bond donor and acceptor groups as well as the bulky aromatic groups for better interactions inside the MMP-2 active site. Meanwhile, the similarities of this current study with our previous observations validate the outcomes of this current study. Hence, these findings may provide useful information toward the development of effective MMP-2 inhibitors in the future.

Separation of monomeric and dimeric phenolic compounds in lignosulphonate lignin on different stationary phases using ultrahigh-performance supercritical fluid chromatography

Lignin is a promising renewable resource and its valorization could help to reduce our dependency on fossil carbon resources. Especially the production of small molecular weight and economically valuable compounds, such as vanillin, are of interest. A good separation of the sample components is crucial for a confident identification of compounds in complex sample mixtures using for instance mass spectrometry. In this work, the resolving power and selectivity of five different stationary phases for ultrahigh-performance supercritical fluid chromatography were studied for the class separation of lignin monomers (LMs) and dimers (LDs). A separation of LMs and LDs will help to identify such compounds in complex technical lignin samples. It could be shown that stationary phases with both hydrogen-bonding acceptor and donator groups offer high overall resolving power, while π-π-interactions are advantageous for the separation of the two compound classes. An almost complete separation combined with an improved overall resolving power was achieved with the 1-aminoanthracene stationary phase, which offers both hydrogen-bonding interactions and π-π-interactions.