Complementary Functional Groups Research Articles

RETRACTED: Amino acid based Rosuvastatin cocrystals: Towards the improvement of physicochemical parameters

• Cocrystal construction between rosuvastatin calcium and amino acids. • Structural and In vitro characterization of cocrystals. • Establishment of intermolecular interaction within the cocrystals. • Cocrystals are found to exhibit higher solubility and dissolution rate. The poor physicochemical properties like low solubility and low dissolution rate of rosuvastatin calcium remain as an obstruction for formulation development. In the present investigation, we explore the evolution of rosuvastatin cocrystal, which may offer the synergetic physico-chemical properties of the drug. Cocrystal crafting depends on two possible intermolecular interactions, heteromeric and the homomeric selection of compounds with complementary functional groups are contemplated as a possible cause of supramolecular synthons in cocrystal formation. Specifically, cocrystals of rosuvastatin with L-asparagine and L-glutamine with molar ratio (1:1) were fabricated by using slow solvent evaporation and solvent evaporation techniques. Novel cocrystals of rosuvastatin-asparagine (RSC-C) and rosuvastatin-glutamine (RSC-G) cocrystals obtained by slow solvent evaporation were utilized for preliminary investigation and further scale-up was done by using the solvent evaporation technique. The novel cocrystals showed a new characteristic of powder X-ray diffraction, thermograms of differential scanning calorimetry, 1 H liquid FT-NMR spectra, and scanning electron microscopy. These results signify, the establishment of intermolecular interaction within the cocrystals. In both the novel cocrystals, rosuvastatin was determined to be engaged in the hydrogen bond interaction with the complementary functional groups of L-asparagine and L-glutamine. Compared with the pure rosuvastatin, RSC-C and RSC-G cocrystal showed 2.17-fold and 1.60-fold improved solubility respectively. The dissolution test showed that the RSC-C and RSC-G cocrystal exhibited 1.64-fold and 1.45-fold higher dissolution rate than the pure rosuvastatin in pH6.8 phosphate buffer respectively. Modulation in the chemical environment, improvement in the solubility and dissolution rate demonstrated the benefit of co-crystallization to improve the physicochemical properties of the drug.

Rosuvastatin cocrystals: an attempt to modulate physicochemical parameters

BackgroundThe meager physicochemical properties like low solubility and low dissolution rate of rosuvastatin calcium remain as an obstruction for formulation development. In the present work, we explore the evolution of rosuvastatin cocrystal, which may offer the synergetic physico-chemical properties of the drug. Cocrystal crafting depends on two possible intermolecular interactions; heteromeric and the homomeric selection of compounds with complementary functional groups are contemplated as a possible cause of supramolecular synthons in cocrystal formation. Specifically, cocrystals of rosuvastatin with l-asparagine and l-glutamine with molar ratio (1:1) were fabricated by using slow solvent evaporation and slow evaporation techniques. Novel cocrystals of rosuvastatin-asparagine (RSC-C) and rosuvastatin-glutamine (RSC-G) cocrystals obtained by slow solvent evaporation were utilized for preliminary investigation and further scale-up was done by using the solvent evaporation technique.ResultsThe novel cocrystals showed a new characteristic of powder X-ray diffraction, thermograms of differential scanning calorimetry, 1H liquid FT-NMR spectra, and scanning electron microscopy. These results signify the establishment of intermolecular interaction within the cocrystals. In both the novel cocrystals, rosuvastatin was determined to be engaged in the hydrogen bond interaction with the complementary functional groups of l-asparagine and l-glutamine. Compared with the pure rosuvastatin, RSC-C and RSC-G cocrystal showed 2.17-fold and 1.60-fold improved solubility respectively. The dissolution test showed that the RSC-C and RSC-G cocrystal exhibited 1.97-fold and 1.94-fold higher dissolution rate than the pure rosuvastatin in pH6.8 phosphate buffer respectively.ConclusionModulation in the chemical environment, improvement in the solubility, and dissolution rate demonstrated the benefit of co-crystallization to improve the physicochemical properties of the drug.Graphical abstract

Variations in Triterpenoid Deposition in Cuticular Waxes during Development and Maturation of Selected Fruits of Rosaceae Family.

The process of fruit ripening involves many chemical changes occurring not only in the mesocarp but also in the epicarp, including changes in the triterpenoid content of fruit cuticular waxes that can modify the susceptibility to pathogens and mechanical properties of the fruit surface. The aim of the study was the determination of the ripening-related changes in the triterpenoid content of fruit cuticular waxes of three plant species from the Rosaceae family, including rugosa rose (Rosa rugosa), black chokeberry (Aronia melanocarpa var. “Galicjanka”) and apple (Malus domestica var. “Antonovka”). The triterpenoid and steroid content in chloroform-soluble cuticular waxes was determined by a GC-MS/FID method at four different phenological stages. The profile of identified compounds was rather similar in selected fruit samples with triterpenoids with ursane-, oleanane- and lupane-type carbon skeletons, prevalence of ursolic acid and the composition of steroids. Increasing accumulation of triterpenoids and steroids, as well as the progressive enrichment of the composition of these compounds in cuticular wax during fruit development, was observed. The changes in triterpenoid content resulted from modifications of metabolic pathways, particularly hydroxylation and esterification, that can alter interactions with complementary functional groups of aliphatic constituents and lead to important changes in fruit surface quality.

Innovative utilization of molecular imprinting technology for selective adsorption and (photo)catalytic eradication of organic pollutants

The rapid development of industrialization and urbanization results in a numerous production of various organic chemicals to meet the increasing demand in high-quality life. During the synthesis and utilization of these chemical products, their residues unavoidably emerged in environments to severely threaten human’s health. It is thus urgent to exploit effective technology for readily removing the organic pollutants with high selectivity and good reusability. As one of the most promising approaches, molecular imprinting technology (MIT) employs a chemically synthetic route to construct artificial recognition sites in highly-crosslinked matrix with complementary cavity and functional groups to target species, which have been attracting more and more interest for environmental remediation, such as the selective adsorption/separation and improved catalytic degradation of pollutants. In this review, MIT is first introduced briefly to understand their preparing process, recognition mechanism and common imprinted systems. Then, their specific binding affinities are demonstrated for selectively adsorbing and removing target molecules with a large capacity. Furthermore, the innovative utilization of MIT in catalytic eradication of pollutants is comprehensively overviewed to emphasize their enhanced efficiency and improved performances, which are classified by the used catalytically-active nanocrystals and imprinted systems. After summarizing recent advances in these fields, some limitations are discussed and possible suggestions are given to guide the future exploitation on MIT for environmental protection.

Quest for Zeolite‐like Supramolecular Assemblies: Self‐Assembly of Metal–Organic Squares via Directed Hydrogen Bonding

AbstractOur conceived approach based on the directed assembly of functional metal–organic squares (MOSs), 4‐membered ring (4MR) building units, permitted the construction of two novel zeolite‐like supramolecular assemblies (ZSAs), namely [Co4(ImDC)4(En)4]⋅9 H2O⋅1.5 DMF (ZSA‐10) and [Co4(ImDC)4(En)4]⋅7 H2O (ZSA‐11) (H3ImDC=4,5‐imidazoledicarboxylic acid, En=ethylenediamine, DMF=N,N‐dimethylformamide). The elected MOSs encompass both trans‐ and cis‐coordinated nodes, offering complementary peripheral functional groups for their directed assembly into zeolite‐like topologies via supramolecular hydrogen bonding interactions. Distinctly, ZSA‐10 possesses the underling MER zeolite topology and is the only pure MER framework material (without any supporting templates) exhibiting permanent porosity up to now. ZSA‐11 has the underlying ABW topology together with one type of narrow channel.

Broadly Applicable Directed Catalytic Reductive Difunctionalization of Alkenyl Carbonyl Compounds

Summary Catalytic alkene difuntionalization is a convenient platform for introducing complexity in molecules and has wide applications in organic synthesis. Yet a compelling challenge that remains to be solved is the regioselective insertion of two highly functionalized carbon-based moieties, derived from stable and readily available organohalide electrophiles without the need for pre-synthesized organometallic reagents, across C=C bonds in unactivated alkyl-substituted alkenes. Here, we show that catalytic amounts of an inexpensive Ni-based catalyst, in combination with a readily recyclable 8-aminoquinoline directing group, promotes efficient and site-selective addition of two different organohalides (iodides and bromides) across aliphatic alkenes under mild reductive conditions. Compared to previous studies, this protocol exhibits broad and complementary functional group tolerance that extends to aryl-alkylation, alkenyl-alkylation, and dialkylation transformations. The utility of the strategy is demonstrated through concise synthesis of biologically active molecules. Kinetic studies and other control experiments shed further light on the mechanistic underpinnings of the multicomponent reaction.

Cocrystals of diacerein: Towards the development of improved biopharmaceutical parameters.

The effectiveness of Diacerein as an anti-osteoarthritis drug is limited due to its acutely poor aqueous solubility and bioavailability. The present study demonstrates cocrystallization as a successful technique to improve the biopharmaceutical parameters of diacerein. Three cocrystals of diacerein were prepared by an eco-friendly technique with three suitable coformers namely isonicotinamide, nicotinamide, and theophylline. The formation of a new solid phase was inferred from the DSC thermograms and powder diffraction pattern and was supported by FTIR. The crystal structures of the cocrystals determined from the PXRD pattern using Material Studio software. Detailed analysis showed the formation of supramolecular hetero-synthons of complementary functional groups of the coformers with the carbonyl and carboxyl groups of diacerein. The structural conformation of the cocrystalline state was also provided by the shifts in the ssNMR pattern of the cocrystals. The three new cocrystals were found to have a relatively high solubility and intrinsic dissolution rate which showed remarkable improvement in anti-arthritic activity as compared to diacerein. Thus, proving cocrystallization to be a potential solution to the solubility limited bioavailability problems of diacerein.

Implication of Coformer Structural Diversity on Cocrystallization Outcomes of Telmisartan with Improved Biopharmaceutical Performance.

Crystal engineering approach was utilized for the development of different multicomponent solid forms of telmisartan (TEL) to improve its oral bioavailability. In this context, two cocrystals, gentisic acid (GA) and maleic acid (MA), while two eutectic mixtures, para-aminobenzoic acid (PABA) and adipic acid (AA), were successfully prepared and characterized by different analytical tools. Both the cocrystals exhibited characteristic heterosynthons, viz. OHacid⋯Narom and OHacid⋯O, to propagate new network. Structural features of coformers has been correlated with the outcomes of cocrystallization approach. Coformers having auxiliary functionality in addition to complementary functional groups have high propensity to generate cocrystals. However, multicomponent where auxiliary functionality is lacking, such combinations, is shown to form eutectic mixtures owing to strong homomeric interaction. Besides, the developed cocrystals and eutectic mixtures showed higher aqueous solubility (3-5.5-fold) and intrinsic dissolution rate (1-2.6-fold) over pure TEL. In vivo studies also revealed significant improvement in relative bioavailability (2-2.6-fold). The study also shed light on the implications of eutectic mixtures in mitigating the solubility issues of drugs which are often considered negative results of cocrystallization strategy.

Induction of Fibrogenic Phenotype in Human Mesenchymal Stem Cells by Connective Tissue Growth Factor in a Hydrogel Model of Soft Connective Tissue.

Scar formation is the typical endpoint of wound healing in adult mammalian tissues. An overactive or prolonged fibrogenic response following injury leads to excessive deposition of fibrotic proteins that promote tissue contraction and scar formation. Although well-defined in the dermal tissue, the progression of fibrosis is less explored in other connective tissues, such as the vocal fold. To establish a physiologically relevant 3D model of loose connective tissue fibrosis, we have developed a synthetic extracellular matrix using hyaluronic acid (HA) and peptidic building blocks carrying complementary functional groups. The resultant network was cell adhesive and protease degradable, exhibiting viscoelastic properties similar to the human vocal fold. Human mesenchymal stem cells (hMSCs) were encapsulated in the HA matrix as single cells or multicellular aggregates and cultured in pro-fibrotic media containing connective tissue growth factor (CTGF) for up to 21 days. hMSCs treated with CTGF-supplemented media exhibited an increased expression of fibrogenic markers and ECM proteins associated with scarring. Incorporation of α-smooth muscle actin into F-actin stress fibers was also observed. Furthermore, CTGF treatment increased the migratory capacity of hMSCs as compared to the CTGF-free control groups, indicative of the development of a myofibroblast phenotype. Addition of an inhibitor of the mitogen-activated protein kinase (MAPK) pathway attenuated cellular expression of fibrotic markers and related ECM proteins. Overall, this study demonstrates that CTGF promotes the development of a fibrogenic phenotype in hMSCs encapsulated within an HA matrix and that the MAPK pathway is a potential target for future therapeutic endeavors towards limiting scar formation in loose connective tissues.

Assembling Ordered Crystals with Disperse Building Blocks.

Conventional colloidal crystallization techniques typically require low dispersity building blocks in order to make ordered particle arrays, resulting in a practical challenge for studying or scaling these materials. Nanoparticles covered in a polymer brush therefore may be predicted to be challenging building blocks in the formation of high-quality particle superlattices, as both the nanoparticle core and polymer brush are independent sources of dispersity in the system. However, when supramolecular bonding between complementary functional groups at the ends of the polymer chains are used to drive particle assembly, these “nanocomposite tectons” can make high quality superlattices with polymer dispersities as large as 1.44 and particle diameter relative standard deviations up to 23% without any significant change to superlattice crystallinity. Here we demonstrate and explain how the flexible and dynamic nature of the polymer chains that comprise the particle brush allows them to deform to accommodate the irregularities in building block size and shape that arise from the inherent dispersity of their constituent components. Incorporating “soft” components into nanomaterials design therefore offers a facile and robust method for maintaining good control over organization when the materials themselves are imperfect.

Design Molecular Topology for Wet-Dry Adhesion.

Recent innovations highlight the integration of diverse materials with synthetic and biological hydrogels. Examples include brain-machine interfaces, tissue regeneration, and soft ionic devices. Existing methods of strong adhesion mostly focus on the chemistry of bonds and the mechanics of dissipation but largely overlook the molecular topology of connection. Here, we highlight the significance of molecular topology by designing a specific bond-stitch topology. The bond-stitch topology achieves strong adhesion between preformed hydrogels and various materials, where the hydrogels have no functional groups for chemical coupling, and the adhered materials have functional groups on the surface. The adhesion principle requires a species of polymer chains to form a bond with a material through complementary functional groups and form a network in situ that stitches with the polymer network of a hydrogel. We study the physics and chemistry of this topology and describe its potential applications in medicine and engineering.

Quinoline analogs of 2-aminoindane as potential central dopaminergic agents

Neurodegenerative disorders such as Parkinson and Huntington Chorea are related with damage to the central dopaminergic system. On the purpose to find new drugs able to re-establish the imbalance on the dopaminergic neurotransmission in the central nervous system and counteract some of the neurodegenerative sicknesses, we have designed, synthesized, pharmacologically evaluated, and studied through molecular modeling,2-aminoindane-quinoline analog derivatives (1–5). Pharmacological studies made on the central nervous system through ICV (intracerebroventricular) and IS (intrastriatal), of compounds (1–5) showed agonistic activity by the activation of dopaminergic mechanisms on the central nervous system. The corresponding molecular modeling study permitted us not only to explain the differential behavior of studied compounds, but also to understand whichmolecular interactions are responsible to stabilize the different complexes formed between those compounds and the D2 receptor. These results validate our medicinal chemical approach in different aspects: the receptor model used, the responsible fragment inserted within the structure of the compounds capable of interacting with the receptor, the complementary functional groups that facilitate the expected response and the pharmacological administration routes. All these aspects are important for the design of this type of compounds as potential anti-Parkinson and/or anti-Huntington agents.

Enhancing Adamantylamine Solubility through Salt Formation: Novel Products Studied by X-ray Diffraction and Solid-State NMR

The reactivity of the neuroleptic drug adamantylamine toward aliphatic carboxylic acids, sulfone derivatives, and aromatic amino acids was screened for the first time using simple mechanochemical methods. Seven new molecular salt structures were reported exhibiting improved physicochemical properties. To carefully characterize these compounds, multiple complementary techniques were combined: single crystal and powder X-ray diffraction, 13C/15N solid-state NMR, and Fourier transform infrared-attenuated total reflectance spectroscopies, employed to solve cocrystal/salt ambiguities. In all molecular salts, the crystal packing is supported on a common synthon, a N–H+(ADA)···O–(coformer) charge assisted hydrogen bond. Different supramolecular arrangements were obtained induced by the size of the counterions as well as their complementary functional groups. Two salts, with glutaric and methanesulfonic acids, presented higher solubility than the commercially available pharmaceutical product.

Complementarity of gymnosperms and angiosperms along an altitudinal temperature gradient

In seasonal tropical forests, evergreen–deciduous mixtures are more productive than monocultures because they intercept more light throughout the year, reflecting complementary resource use by functional groups possessing different traits. This suggests that temperate and boreal forests may also exhibit overyielding, due to the difference in phenology between gymnosperms and angiosperms. However, complementarity could also arise from differences in morphology between needle leaves and broad leaves, or facilitation by N‐fixing species. Alternatively, mixtures may be more productive simply because interspecific competition is less intense than intraspecific competition. We used forest inventory data to assess the complementarity of the main functional groups in Switzerland. We employed a trait‐based analysis of competition to determine whether: 1) trait differences reduce the intensity of competition between complementary functional groups, 2) complementarity is observed along a broad altitudinal temperature gradient. N‐fixing species facilitated the growth of non‐fixing species, such that 50/50 mixtures were 50% more productive than monocultures, though half the overyielding was due to the alleviation of intraspecific competition. In contrast, we found no evidence of complementarity between evergreen and deciduous species. For example, in stands where larch was mixed with other gymnosperms, there was no reduction in heterospecific competition among evergreen species, even though evergreens cast shade on one another throughout the year. In cold montane forests, broadleaf species reduced the suppression of needleleaf species, and vice versa. Thus, 50/50 mixtures of needleleaf and broadleaf species were 15% more productive than needleleaf monocultures. However, in warm lowland forests, broadleaf species exacerbated the suppression of needleleaf species, completely offsetting the positive effect that needleleaf species had on broadleaf species. In summary, we found no evidence of complementarity between evergreen and deciduous species, but needleleaf–broadleaf mixtures exhibited overyielding in cold montane forests, which is consistent with the stress gradient hypothesis, though the underlying mechanisms remain uncertain.

Molecularly Imprinted Polymers for the Selective Extraction of Bisphenol A and Progesterone from Aqueous Media.

This paper describes the development of a novel sorbent for selective extraction of endocrine disruptors (EDs) from aqueous media. The main goal was to obtain sufficient molecularly imprinted polymers (MIPs) for selective detection, preconcentration, and extraction of EDs such as bisphenol A (BPA) and progesterone (PG). Series of MIPs and their analogues, non-molecularly imprinted polymers (NIPs), were synthesised following a non-covalent imprinting strategy based on radical polymerisation. Sets of synthesis were performed in order to optimise variables of the polymerisation including solvent, cross-linker, and template ratio. The retention capacity of MIPs was determined using HPLC in the range of 33.3% to 96.6% and 32.5% to 96% for BPA and PG, respectively. The adsorption mechanism was studied by isothermal and kinetic assays. The kinetic analysis showed a high retention capacity within 15 min of contact. The polymer yield was obtained in the range of 30% to 100%. Additionally, there was no significant cross-reactivity observed upon testing MIPs with structural analogues and other endocrine disruptors instead of target molecules. The results also revealed the high importance of different concentrations of cross-linker and solvent during the polymerisation. Firstly, the pre-organisation of complementary functional groups, which were present in the polymerisation mixture, and secondly, selective cavity formation for target molecules.

Exploring Exchange Bias Coupling in Fe3−δO4@CoO Core–Shell Nanoparticle 2D Assemblies

AbstractCore‐shell ferro(i)magnetic@antiferromagnetic (F(i)M@AFM) nanoparticles exhibiting exchange bias coupling are very promising to push back the superparamagnetic limits. However, their intrinsic magnetic properties can be strongly affected by interparticle interactions. This work reports on the collective properties of Fe3–dO4@CoO core‐shell nanoparticles as function of the structure of their assembly. The structure of nanoparticle assembly is controlled by a copper (I) catalyzed alkyne–azide cycloaddition (CuAAC) “click” reaction between complementary functional groups located at the surface of both substrates and nanoparticles. 2D arrays of nanoparticles with tunable sizes ranging from clusters of few nanoparticles to a dense and homogenous monolayer were prepared. The spatial arrangement of nanoparticles strongly influences the exchange bias coupling which is significantly enhanced for large 2D nanoparticle assemblies and, even more in 3D assemblies such as powder, which favour weak and random dipolar interactions.

Fluorescence Quenching of CdTe Quantum Dots with Co (III) Complexes via Electrostatic Assembly Formation

Abstract The photoluminescence quenching of CdTe QDs in the presence of three different Co (III)-complexes is studied to elucidate the role of interactions between functional groups of positively charged cysteamine capped CdTe QDs and negatively charged Co (III) complexes bearing carboxylic groups. The steady state and time resolved spectroscopy has been used to investigate the mechanism of quenching. After detailed analysis, it is concluded that quenching is contributed by both static as well as dynamic processes. The static contribution has been assigned to the electrostatic assembly formation via ionic interactions between the amine functional groups of positively charged cysteamine capped CdTe QDs and carboxylic acid groups of negatively charged complexes. The electrostatic interactions were confirmed by zeta potential measurement as well as from effect of salt addition. These studies have implications in designing donor/acceptor pairs having complementary functional groups for efficient optoelectronic devices or photocatalytic systems.

Reconfigurable Printed Liquids.

Liquids lack the spatial order required for advanced functionality. Interfacial assemblies of colloids, however, can be used to shape liquids into complex, 3D objects, simultaneously forming 2D layers with novel magnetic, plasmonic, or structural properties. Fully exploiting all-liquid systems that are structured by their interfaces would create a new class of biomimetic, reconfigurable, and responsive materials. Here, printed constructs of water in oil are presented. Both form and function are given to the system by the assembly and jamming of nanoparticle surfactants, formed from the interfacial interaction of nanoparticles and amphiphilic polymers that bear complementary functional groups. These yield dissipative constructs that exhibit a compartmentalized response to chemical cues. Potential applications include biphasic reaction vessels, liquid electronics, novel media for the encapsulation of cells and active matter, and dynamic constructs that both alter, and are altered by, their external environment.

Dynamic covalent chemistry enables formation of antimicrobial peptide quaternary assemblies in a completely abiotic manner.

Naturally occurring peptides and proteins often use dynamic disulfide bonds to impart defined tertiary/quaternary structures for the formation of binding pockets with uniform size and function. Although peptide synthesis and modification are well established, controlling quaternary structure formation remains a significant challenge. Here, we report the facile incorporation of aryl aldehyde and acyl hydrazide functionalities into peptide oligomers via solid-phase copper-catalysed azide-alkyne cycloaddition (SP-CuAAC) click reactions. When mixed, these complementary functional groups rapidly react in aqueous media at neutral pH to form peptide-peptide intermolecular macrocycles with highly tunable ring sizes. Moreover, sequence-specific figure-of-eight, dumbbell-shaped, zipper-like and multi-loop quaternary structures were formed selectively. Controlling the proportions of reacting peptides with mismatched numbers of complementary reactive groups results in the formation of higher-molecular-weight sequence-defined ladder polymers. This also amplified antimicrobial effectiveness in select cases. This strategy represents a general approach to the creation of complex abiotic peptide quaternary structures.

Long, self-assembled molecular ladders by cooperative dynamic covalent reactions

The dynamic covalent self-assembly of peptoid-based oligomers bearing n complementary functional groups yields molecular ladders with n covalent rungs.