Use Of Supramolecular Assemblies Research Articles

Enhancing antibacterial efficacy through macrocyclic host complexation of fluoroquinolone antibiotics for overcoming resistance

The use of supramolecular assemblies in pharmaceuticals has garnered significant interest. Recent studies have shown that the activities of antibacterial agents can be enhanced through complexation with cyclic oligomers and metal ions. Notably, these complexes sometimes possess greater therapeutic properties than the parent drugs. To develop microbiologically potent supramolecular drugs, the complexation of macrocyclic hosts with fluoroquinolone (FQ) antibiotics was investigated. FQs are a successful family of antibiotics that target the bacterial enzymes DNA gyrase and DNA topoisomerase IV, leading to bacterial cell death through the inhibition of DNA synthesis. However, antibiotic resistance resulting from the repeated use of FQs over time has limited their effectiveness against resistant pathogens. To overcome this issue, the encapsulation of FQs in polyphenolic macrocycles was investigated. This study highlights resorcinarene, a polyphenolic host with antibacterial properties, and its ability to chemically interact with FQs. The inclusion complexation process was analyzed using NMR and FTIR techniques. The binding constants determined by 1H-NMR titration revealed that levofloxacin forms more stable complexes with resorcinarene than with β-cyclodextrin, which aligned with MD simulations. Assessment of the geometric characteristics of the inclusion complexes using 2D NMR analysis confirmed that different moieties of various FQs can fit into a single host cavity and improve activity against gram-negative bacteria. Overall, these findings suggest that encapsulation in polyphenolic macrocycles is a promising strategy for utilizing FQs against antibiotic-resistant bacteria.

Melamine Barbiturate as a Light-Induced Nanostructured Supramolecular Material for a Bioinspired Oxygen and Organic Radical Trap and Stabilization.

Use of coantioxidant systems is a prospective way to increase the effectiveness of antioxidant species in tissue repair and regeneration. In this paper, we introduce a novel scheme of a reactive oxygen species (ROS) trap and neutralization during self-assembly of supramolecular melamine barbiturate material. The performed reaction chain mimics the biological process of ROS generation in key stages and enables one to obtain stable hydroperoxyl and organic radicals in a melamine barbiturate structure. Melamine barbiturate also neutralizes hydroxyl radicals, and the effectiveness of the radical trap is controlled with ROS scavenger incorporation. The number of radicals dramatically increases during light-inducing and depends on pH. The proposed scheme of the ROS trap and neutralization opens a way to the use of supramolecular assemblies as a component of coantioxidant systems and a source of organic radicals.

Graphene-Porphyrin Supramolecular Assemblies and Their Consequences in Organic Photovoltaic Cells

Organic photovoltaic cells based on porphyrins, regardless they are small molecules or placed within a conjugated polymer backbone, have become increasingly more performants over the past few years (Solar RRL, 2017, 1, 1-26; Solar RRL, 2018, 2, 1-9; ACS Applied Materials & Interfaces, 2018, 10, 992-1004; ChemPlusChem, 2017, 82, 625-630; ACS Applied Materials & Interfaces, 2019, 11, 28078-28087). In the bulk heterojunction structure, the porphyrin chromophores act as both antennas for exciton energy migration and energy transfer, and as electron donors. At the interfaces of the electron donor and acceptor phases, supramolecular contacts between the porphyrin pigments and electron acceptors occurs. Among the electron acceptors, carbon-based semi-conducting materials such as fullerene- and graphene-type species represent the largest group. Although these photophysical processes at the are deduced from the macroscopic scale behaviors of the solar cells and the use of molecular models where the donor and acceptors of energy and electron are covalently bonded together (Phys. Chem. Chem. Phys. 2017, 19, 24018-24028; Dalton Trans. 2017, 46, 6278-6290; Phys. Chem. Chem. Phys. 2017, 19, 2926-2939), the use of supramolecular assemblies as models is rather limited to a few examples and suffer from the unavoidable weak binding constant of the p-stacked donor-acceptor dyads in solution (Inorg. Chem. 2016, 55, 9230-9239). This weak donor-acceptor binding results in an undesired mixture of assembled and free species in solution rendering the analysis somewhat difficult and often unreliable. The design of more realistic models requires robust anchoring molecular devices using moieties that do not interfere with the photophysical behaviors of the assemblies. Graphene is certainly a good electron acceptor, but the preparation of rigorously reduced graphene is tedious. Concurrently, the alternative is to use reduced graphene oxide but suffers from the poor solubility, and perhaps the presence of oxidized fragments on the graphene sheet. To overcome these inconveniences, the use of nanoribbons of graphene, where soluble groups flank the sides of the ribbons and the graphene segment is free of oxidized portions, appears ideal. The selected anchoring groups are two pyrenes to secure stable assemblies of porphyrin dyes and allowing a coverage of 30% of the available surface. This presentation focusses on the syntheses and characterization of the nanoribbons and their assemblies with zincporphyrin pigments. These assemblies form charge transfer excited states (CT states) and a detailed investigation of their photophysical properties addressing the various processes, namely excitation energy migration, energy (including nanoribbon to zincporphyrin CT state) and electron transfers, is made. These events can be ultrafast often smaller than 1 ps, but also sometime occurring well within the laser pulse, which can be within the 100-150 fs. At first glance these ultrafast events suggest that the photoconversion efficiency, PCE, can not limited by the time scale of these events, but the occurrence of competitive excited state relaxations and back electron transfers also being ultrafast (several hundreds of ps), can contribute in reducing the production of charge separated Frenkel species at the donor-electron interfaces. In these soluble models, it is interesting to discover that the graphene nanoribbons can also act as antennas permitting more photons to be harvested, which subsequently promote energy transfer to the CT assemblies, thus increasing the relative amount of excited CT states at the interfaces (J. Phys. Chem. C 2020, 124, 16248-16260). The creation of these charge transfer assemblies turns out to play a dominant role in their resulting photophysical traits and the enhancement of such CT states in terms of relative amount and spectral position in the red region, can be modulated upon using the push-pull conjugated polymers. The synthesis of such type of conjugated polymers is tricky (J. Org. Chem. 2019, 84, 3590-3594; Macromolecules 2015, 48, 7024-7038; Chem. Commun. 2011, 47, 10942-10944) and will be briefly discussed. Figure 1

Carbon Nanotubes: An Emerging Drug Delivery Carrier in Cancer Therapeutics.

The scope of nanotechnology has been extended to almost every sphere of our daily life. As a result of this, nanocarriers like Carbon Nanotubes (CNTs) are gaining considerable attention for their use in various therapeutic and diagnostic applications. The objective of the current article is to review various important features of CNTs that make them as efficient carriers for anticancer drug delivery in cancer therapeutics. In this review article, different works of literature are reported on various prospective applications of CNTs in the targeting of multiple kinds of cancerous cells of different organs via; the loading of various anticancer agents. Actually, CNTs are the 3rd allotropic type of the carbon-fullerenes that are a part of the cylindrical tubular architecture. CNTs possess some excellent physicochemical characteristics and unique structural features that provide an effective platform to deliver anticancer drugs to target specific sites for achieving a high level of therapeutic effectiveness even in cancer therapeutics. For better results, CNTs are functionalized and modified with different classes of therapeutically bioactive molecules via; the formation of stable covalent bonding or by the use of supramolecular assemblies based on the noncovalent interaction(s). In recent years, the applications of CNTs for the delivery of various kinds of anticancer drugs and targeting of tumor sites have been reported by various research groups. CNTs represent an emerging nanocarrier material for the delivery and targeting of numerous anticancer drugs in cancer therapeutics.

Facile morphology control of gold(0) structures from aurophilic assemblies.

Different gold microstructures have been synthesized by using supramolecular gold(i) organometallic compounds as templates and Ag nanoparticles as reducing agents. The use of fibers resulting from supramolecular assemblies of neutral gold(i) compounds gives rise to the formation of microrods. The use of supramolecular assemblies from ionic molecules results in spherical or square-based prism gold microstructures, depending on the shape of the supramolecular gold(i) precursor assembly. In addition to temperature and reaction time, solvents exert a strong influence on the formation and morphology of gold structures, as borne out by the example that well-defined star-like morphologies have been obtained in chloroform.

Instructed Assembly of Peptides for Intracellular Enzyme Sequestration.

Liquid-like droplets of biomacromolecules are emerging as a fundamental mechanism of cellular signaling, but designing synthetic mimics to form such membraneless organelles remains unexplored. Here we report the use of supramolecular assemblies of small peptides, as a mimic of biomacromolecular condensates, for intracellular sequestration of enzymes on endoplasmic reticulum (ER). Specifically, integrating a short peptide with naproxen (a nonsteroidal anti-inflammatory drug (NSAID) and a ligand of cyclooxygenase-2 (COX-2)) generates an enzymatic substrate that acts as a precursor for instructed assembly. Slowly dephosphorylating the precursors by phosphatases forms the corresponding hydrogelators in a cellular environment, which results in the supramolecular assemblies on ER. Consisting of the precursor and the hydrogelator molecules, the assemblies enable the sequestration of COX-2 and protein-tyrosine phosphatase 1B (PTP1B) on ER. Further structure-activity investigation reveals that the colocalization of COX-2 and PTP1B relies on the NSAID motif, the phosphotyrosine, and the enzymatic dephosphorylation of the precursor. This work, for the first time, illustrates the use of supramolecular processes for associating enzymes in cells and may provide insights for understanding intracellular liquid condensates and a new strategy for modulating protein-protein interactions.

Adaptive Multifunctional Supramolecular Assemblies of Glycopeptides Rapidly Enable Morphogenesis.

Despite the well-established biophysical principle of adhesion-guided in vitro morphogenesis, there are few single synthetic molecular species that can rapidly enable morphogenesis (e.g., a cell monolayer to cell spheroids) in a cell culture because adhesion inherently involves many signals. Here we show the use of adaptive multifunctional supramolecular assemblies of glycopeptides, consisting of cell adhesion sequence and saccharide, to induce cell spheroids rapidly from a monolayer of cells. Having a general architecture of N-terminal capping, glycosylation, and an integrin-binding sequence, the glycopeptides self-assemble to form a dynamic continuum of nanostructures (i.e., from nanoparticles to nanofibers) to affect the interactions of integrins, E-selectin, and cadherins with their natural ligands and to act adaptively according to the cellular environment. Such adaptive (i.e., context-dependent) interactions weaken cell-substratum adhesion and enhance intercellular interactions, which rapidly and transiently induce cell spheroids. This work illustrates the use of supramolecular assemblies of simple glycopeptides to modulate biophysical conditions for regulating cell functions, which is a new approach for developing biomaterials.

Nucleopeptide Assemblies Selectively Sequester ATP in Cancer Cells to Increase the Efficacy of Doxorubicin

AbstractHerein, we report that assemblies of nucleopeptides selectively sequester ATP in complex conditions (for example, serum and cytosol). We developed assemblies of nucleopeptides that selectively sequester ATP over ADP. Counteracting enzymes interconvert ATP and ADP to modulate the nanostructures formed by the nucleopeptides and the nucleotides. The nucleopeptides, sequestering ATP effectively in cells, slow down efflux pumps in multidrug‐resistant cancer cells, thus boosting the efficacy of doxorubicin, an anticancer drug. Investigation of 11 nucleopeptides (including d‐ and l‐enantiomers) yields five more nucleopeptides that differentiate ATP and ADP through either precipitation or gelation. As the first example of assemblies of nucleopeptides that interact with ATP and disrupt intracellular ATP dynamics, this work illustrates the use of supramolecular assemblies to interact with small and essential biological molecules for controlling cell behavior.

Nucleopeptide Assemblies Selectively Sequester ATP in Cancer Cells to Increase the Efficacy of Doxorubicin.

Herein, we report that assemblies of nucleopeptides selectively sequester ATP in complex conditions (for example, serum and cytosol). We developed assemblies of nucleopeptides that selectively sequester ATP over ADP. Counteracting enzymes interconvert ATP and ADP to modulate the nanostructures formed by the nucleopeptides and the nucleotides. The nucleopeptides, sequestering ATP effectively in cells, slow down efflux pumps in multidrug-resistant cancer cells, thus boosting the efficacy of doxorubicin, an anticancer drug. Investigation of 11 nucleopeptides (including d- and l-enantiomers) yields five more nucleopeptides that differentiate ATP and ADP through either precipitation or gelation. As the first example of assemblies of nucleopeptides that interact with ATP and disrupt intracellular ATP dynamics, this work illustrates the use of supramolecular assemblies to interact with small and essential biological molecules for controlling cell behavior.

Richard Winpenny

Richard Winpenny

Use of Supramolecular Assemblies as Lithographic Resists

AbstractA new resist material for electron beam lithography has been created that is based on a supramolecular assembly. Initial studies revealed that with this supramolecular approach, high‐resolution structures can be written that show unprecedented selectivity when exposed to etching conditions involving plasmas.

Use of Supramolecular Assemblies as Lithographic Resists.

A new resist material for electron beam lithography has been created that is based on a supramolecular assembly. Initial studies revealed that with this supramolecular approach, high-resolution structures can be written that show unprecedented selectivity when exposed to etching conditions involving plasmas.

A Discrete Supramolecular Conglomerate Composed of Two Saddle‐Distorted Zinc(II)‐Phthalocyanine Complexes and a Doubly Protonated Porphyrin with Saddle Distortion Undergoing Efficient Photoinduced Electron Transfer

Porphyrins (Por) and phthalocyanines (Pc) exhibit lightharvesting efficiency for producing charge-separated states as models of the reaction center in photosynthetic bacteria and photovoltaic cells for energy conversion. The use of supramolecular assemblies to model the functionality of the reaction center is an attractive and fruitful strategy to develop photofunctional materials and devices. Porphyrins exhibit strong Soret bands around 400 to 450 nm, whereas phthalocyanines show strong Q bands around 700 to 800 nm. Thus, the combination of those two p systems can cover nearly the whole range of the visible region and can be a useful strategy for development of photofunctional materials for efficient light-energy conversion. Attempts have so far been made to synthesize covalently linked Por–Pc heterodyad molecules and construct Por–Pc heterosupramolecules. Recently, ZnPor and ZnPc have been reported to form two-dimensional arrays on gold surfaces, and the formation of a cofacial ZnPor–ZnPc coordination tetrad has also been reported. However, a crystal structure determination of a discrete supramolecular assembly composed of both Por and Pc has yet to be reported. In addition, since the Q-band absorption of Pc usually overlaps the wavelength of fluorescence of Por, energy transfer is favored over electron transfer in most heterodyads. We have developed supramolecular assemblies based on a saddle-distorted nonplanar porphyrin, dodecaphenylporphyrin (H2DPP), and its metal complexes. [11–13] The saddle distortion facilitates protonation of pyrrole nitrogen atoms to allow access to a stable diprotonated porphyrin, which can act as an electron acceptor. In addition, the saddle distortion affords higher Lewis acidity at the metal center to maintain axial coordination of ligands, as a result of poor overlap of the pyrrole nitrogen lone pair orbitals with d orbitals of the metal center. In contrast, the Zn complex of the saddle-distorted phthalocyanine 1,4,8,11,15,18,22,25-octaphenylphthalocyanine (H2OPPc) exhibits a lower oxidation potential relative to the corresponding porphyrin complex. To construct supramolecular conglomerates composed of both porphyrin and phthalocyanine in a well-defined manner, we have taken advantage of saddle distortion of both components. Herein, we report formation of a discrete supramolecular assembly composed of H4DPP 2+ and [Zn(OPPc)] connected by 4-pyridinecarboxylate (4-PyCOO ) with coordination and hydrogen bonding (Figure 1). The supramolecular conglomerate [(H4DPP){Zn(OPPc)(k-N-4-PyCOO)}2] (1) was synthesized by reaction of [H4DPP](4-PyCOO)2 (2) and Zn(OPPc) (3) in toluene. We crystallized and isolated 1 in pure form by vapor diffusion of hexanes into solution of the mixture in toluene. X-ray crystallography of 1 unambiguously established its structure (Figure 2a).

Progress in the characterization of synthetic (supramolecular) polymers by analytical ultracentrifugation.

Analytical ultracentrifugation (AUC) is the leading technique for determining the molar mass, state of association in solution, and association constants of biological macromolecules. Even though it is little used for supramolecular polymers, this technique has already been shown to represent one of the best options in the characterization of these systems. The use of supramolecular assemblies in the field of nanotechnology requires the arrangement of such systems on surfaces, from solution. Therefore, the control and investigation of solution properties is of major importance. In this contribution we highlight the applicability and advantages of using AUC by presenting a summary of the results of the past few years on the characterization of various types of synthetic polymers and supramolecular polymer systems.