Hydrophilic Capping Research Articles

Nano-Antibacterials Using Medicinal Plant Components: An Overview.

Gradual emergence of new bacterial strains, resistant to one or more antibiotics, necessitates development of new antibacterials to prevent us from newly evolved disease-causing, drug-resistant, pathogenic bacteria. Different inorganic and organic compounds have been synthesized as antibacterials, but with the problem of toxicity. Other alternatives of using green products, i.e., the medicinal plant extracts with biocompatible and potent antibacterial characteristics, also had limitation because of their low aqueous solubility and therefore less bioavailability. Use of nanotechnological strategy appears to be a savior, where phytochemicals are nanonized through encapsulation or entrapment within inorganic or organic hydrophilic capping agents. Nanonization of such products not only makes them water soluble but also helps to attain high surface to volume ratio and therefore high reaction area of the nanonized products with better therapeutic potential, over that of the equivalent amount of raw bulk products. Medicinal plant extracts, whose prime components are flavonoids, alkaloids, terpenoids, polyphenolic compounds, and essential oils, are in one hand nanonized (capped and stabilized) by polymers, lipids, or clay materials for developing nanodrugs; on the other hand, high antioxidant activity of those plant extracts is also used to reduce various metal salts to produce metallic nanoparticles. In this review, five medicinal plants, viz., tulsi (Ocimum sanctum), turmeric (Curcuma longa), aloe vera (Aloe vera), oregano (Oregano vulgare), and eucalyptus (Eucalyptus globulus), with promising antibacterial potential and the nanoformulations associated with the plants’ crude extracts and their respective major components (eugenol, curcumin, anthraquinone, carvacrol, eucalyptus oil) have been discussed with respect to their antibacterial potency.

Molecular, Solid-State and Surface Structures of the Conformational Polymorphic Forms of Ritonavir in Relation to their Physicochemical Properties

PurposeApplication of multi-scale modelling workflows to characterise polymorphism in ritonavir with regard to its stability, bioavailability and processing.MethodsMolecular conformation, polarizability and stability are examined using quantum mechanics (QM). Intermolecular synthons, hydrogen bonding, crystal morphology and surface chemistry are modelled using empirical force fields.ResultsThe form I conformation is more stable and polarized with more efficient intermolecular packing, lower void space and higher density, however its shielded hydroxyl is only a hydrogen bond donor. In contrast, the hydroxyl in the more open but less stable and polarized form II conformation is both a donor and acceptor resulting in stronger hydrogen bonding and a more stable crystal structure but one that is less dense. Both forms have strong 1D networks of hydrogen bonds and the differences in packing energies are partially offset in form II by its conformational deformation energy difference with respect to form I. The lattice energies converge at shorter distances for form I, consistent with its preferential crystallization at high supersaturation. Both forms exhibit a needle/lath-like crystal habit with slower growing hydrophobic side and faster growing hydrophilic capping habit faces with aspect ratios increasing from polar-protic, polar-aprotic and non-polar solvents, respectively. Surface energies are higher for form II than form I and increase with solvent polarity. The higher deformation, lattice and surface energies of form II are consistent with its lower solubility and hence bioavailability.ConclusionInter-relationship between molecular, solid-state and surface structures of the polymorphic forms of ritonavir are quantified in relation to their physical-chemical properties.

A Grand Avenue to Au Nanocluster Electrochemiluminescence.

In most cases of semiconductor quantum dot nanocrystals, the inherent optical and electrochemical properties of these interesting nanomaterials do not translate into expected efficient electrochemiluminescence or electrogenerated chemiluminescence (ECL) because of the surface-state induction effect. Thus, their low ECL efficiencies, while very interesting to explore, limit their applications. As their electrochemistry is not well-defined, insight into their ECL mechanistic details is also limited. Alternatively, gold nanoclusters possess monodispersed sizes with atomic precision, low and well defined HOMO-LUMO energy gaps, and stable optical and electrochemical properties that make them suitable for potential ECL applications. In this Account, we demonstrate strong and sustainable ECL of gold nanoclusters Au25z (i.e., Au25(SR)18z, z = 1-, 0, 1+), Au38(SR)24, and Au144(SR)60, where the ligand SR is 2-phenylethanethiol. By correlation of the optical and electrochemical features of Au25 nanoclusters, a Latimer-type diagram can be constructed to reveal thermodynamic relationships of five oxidation states (Au252+, Au25+, Au250, Au25-, and Au252-) and three excited states (Au25-*, Au250*, and Au25+*). We describe ECL mechanisms and reaction kinetics by means of conventional ECL-voltage curves and novel spooling ECL spectroscopy. Notably, their ECL in the presence of tri-n-propylamine (TPrA), as a coreactant, is attributed to emissions from Au25-* (950 nm, strong), Au250* (890 nm, very strong), and Au25+* (890 nm, very strong), as confirmed by the photoluminescence (PL) spectra of the three Au25 clusters electrogenerated in situ. The ECL emissions are controllable by adjustment of the concentrations of TPrA· and Au25-, Au250, and Au25+ species in the vicinity of the working electrode and ultimately the applied potential. It was determined that the Au25-/TPrA coreactant system should have an ECL efficiency of >50% relative to the Ru(bpy)32+/TPrA, while those of Au250/TPrA and Au25+/TPrA reach 103% and 116%, respectively. Au25-* is the main light emission source for Au25z in the presence of benzoyl peroxide (BPO) as a coreactant, with a relative efficiency of up to 30%. For Au38, BPO leads to the Au38-* excited state, which emits light at 930 nm. In the Au38/TPrA coreactant system, we find that highly efficient light emission at 930 nm is mainly from Au38+* (and also Au383+*), with an efficiency 3.5 times that of the Ru(bpy)32+/TPrA reference. We show that the ECL and PL of the various Au38 charge states, namely, Au382-, Au38-, Au380, Au38+, Au382+, and Au384+, have the same peak wavelength of 930 nm. Finally, we demonstrate ECL with a peak wavelength of 930 nm from the Au144/TPrA coreactant system, which is released from the electrogenerated excited states Au144+* and Au1443+*. In our opinion, these gold nanoclusters represent a new class of effective near-IR ECL emitters, from which applications such as bioimaging, biological testing, and medical diagnosis are anticipated once they are made water-dispersible with hydrophilic capping ligands.

High-Quality Water-Soluble Core/Shell/Shell CdSe/CdS/ZnS Quantum Dots Balanced by Ionic and Nonionic Hydrophilic Capping Ligands

Pentaerythritol tetrakis 3-mercaptopropionate (PTMP) grafted poly(acryl acid) (PAA) ionic hydrophilic oligomer PAA-PTMP (PP) and dihydrolipoic acid (DHLA) grafted methoxypoly(ethylene glycol) (mPEG) nonionic hydrophilic oligomer mPEG-DHLA (PD) have been designed, synthesized and used as co-capping ligands in water-solubilization of hydrophobic quantum dots (QDs) via ligand exchange. The obtained oligomers with multi-thiol groups could bind strongly to the surface atoms of QDs. Meanwhile, the carboxyl groups (from PP) and mPEG segment (from PD) can render QDs water-soluble, and the free carboxylic groups can possibly be used for the further bioconjugation. The resulting water-soluble QDs have been characterized by ultraviolet-visible (UV-Vis), fluorescence, Fourier transform infrared (FTIR) spectroscopy as well as transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. The water-soluble QDs have relatively small hydrodynamic size (10[Formula: see text]12 nm), and importantly, retain high fluorescence quantum yields (up to 45%) compared with that of the originally hydrophobic QDs (49%). In addition, they have tunable surface charges and show excellent colloidal stability over a relatively broad pH range ([Formula: see text]), in high salt concentration, and even after thermal treatment at 100[Formula: see text]C. These results indicate that the water-soluble QDs coated by PP and PD oligomers have potential applications in cellular imaging and biosensor.

Green Synthesis of High-Purity Mesoporous Gold Sponges Using Self-Assembly of Gold Nanoparticles Induced by Thiolated Poly(ethylene glycol).

A facile and green synthesis method for mesoporous gold sponges has been developed, which involves a simple mixing of a very small amount of thiolated-poly(ethylene glycol) (SH-PEG) and citrate-covered gold nanoparticles (Au NPs) in aqueous solution at room temperature. While SH-PEG molecules have been widely used as biocompatible hydrophilic capping agents for Au NPs for stable dispersion in aqueous solution, here they are used as destabilizing agents. When SH-PEG molecules are mixed with citrate-covered Au NPs at the molar ratio ranging from 3 to 20 (SH-PEG/Au NP), mesoporous gold sponges with randomly interconnected 3D network structures are formed within 2 to 3 h. This is driven by the destabilization of negatively charged citrate molecules on Au NPs by a small number of SH-PEG molecules bonded on the particle surface, which results in the decrease in zeta potential and thus the assembly of Au NPs into porous sponges. The use of very low concentration of SH-PEG (ca. 20-200 nM) in aqueous solution at room temperature makes the method highly eco-friendly as well as results in high-purity as-synthesized gold sponges (98.7 wt %). The mesoporous gold sponges fabricated with the present method exhibit a high SERS activity, making them highly applicable for sensitive SERS detection of molecules.

A simple strategy to improve the interfacial activity of true Janus gold nanoparticles: a shorter hydrophilic capping ligand.

Janus gold nanoparticles (JPs) of ∼4 nm-diameter half functionalized with 1-hexanethiol as a hydrophobic capping ligand exhibit significantly higher interfacial activity, reproducibility and rheological response when the other half is functionalized with 1,2-mercaptopropanediol (JPs-MPD) than with 2-(2-mercaptoethoxy)ethanol (JPs-MEE), both acting as hydrophilic capping ligands. The interfacial pressure measured by pendant drop tensiometry reaches 50 mN m(-1) and 35 mN m(-1) for the JPs-MPD at the water/air and water/decane interface, respectively. At the same area per particle, the JPs-MEE reveal significantly lower interfacial pressure: 15 mN m(-1) and 5 mN m(-1) at the water/air and water/decane interface, respectively. Interfacial dilatational rheology measurements also show an elastic shell behaviour at higher compression states for JPs-MPD while the JPs-MEE present near-zero elasticity. The enhanced interfacial activity of JPs-MPD is explained in terms of chemical and hydration differences between the MPD and MEE ligands, where MPD has a shorter hydrocarbon chain and twice as many hydroxyl terminal groups as MEE.

Tailoring Cellular Uptake of Conjugated Polymer Nanoparticles Using Modular Amphiphilic Peptide Capping Ligands

Conjugated polymers possess excellent qualities as fluorescent probes for biomedical applications, because of their extremely high brightness, extinction coefficients, and photostability. Encapsulating these hydrophobic polymers in nanoparticulate form allows transfer to aqueous environments and construction of high-performance fluorescent nanoparticle constructs, and several surface capping strategies have been demonstrated to date. Here, we describe the development of a new class of multifunctional capping ligands for conjugated polymer nanoparticles based on custom-designed amphiphilic peptides. These versatile peptide ligands provide a protective hydrophilic capping layer, chemical handles for further conjugation, and directed biological activity tuned by altering the specific amino acid sequence. We show that (i) cellular uptake can be regulated as a function of peptide composition, and (ii) the nanoparticles show no signs of toxicity under the conditions used, which is a vital health and environment...

The “Needle in the Haystack” Makes the Difference: Linear and Hyperbranched Polyglycerols with a Single Catechol Moiety for Metal Oxide Nanoparticle Coating

Multifunctional linear (CA-linPG) and hyperbranched polyglycerols (CA-hbPG) bearing a single catechol unit were synthesized by use of an acetonide-protected catechol initiator for the anionic polymerization of ethoxyethyl glycidyl ether (EEGE) and glycidol, respectively. A key feature for the synthesis of the hyperbranched structures was a selective, partial acetal deprotection step. The single catechol unit among a large number of aliphatic 1,2- and 1,3-diol moieties (i.e., the “needle in the haystack”) in both linear and hyperbranched polyglycerols permits dispersion of transition metal oxide nanoparticles in brine, as demonstrated for manganese oxide (MnO) nanoparticles. Molecular weights of the single catechol bearing PGs ranged from 950 to 2350 g·mol–1 for CA-linPG and from 3750 to 5750 g·mol–1 for CA-hbPG with narrow and monomodal molecular weight distributions (Mw/Mn < 1.23 for linPG and Mw/Mn = 1.22–1.48 for hbPG). Both C-linPGs and C-hbPGs are suitable hydrophilic capping agents to generate highl...

Self-association of TPR domains: Lessons learned from a designed, consensus-based TPR oligomer

The tetratricopeptide repeat (TPR) motif is a protein-protein interaction module that acts as an organizing centre for complexes regulating a multitude of biological processes. Despite accumulating evidence for the formation of TPR oligomers as an additional level of regulation there is a lack of structural and solution data explaining TPR self-association. In the present work we characterize the trimeric TPR-containing protein YbgF, which is linked to the Tol system in Gram-negative bacteria. By subtracting previously identified TPR consensus residues required for stability of the fold from residues conserved across YbgF homologs, we identified residues involved in oligomerization of the C-terminal YbgF TPR domain. Crafting these residues, which are located in loop regions between TPR motifs, onto the monomeric consensus TPR protein CTPR3 induced the formation of oligomers. The crystal structure of this engineered oligomer shows an asymmetric trimer where stacking interactions between the introduced tyrosines and displacement of the C-terminal hydrophilic capping helix, present in most TPR domains, are key to oligomerization. Asymmetric trimerization of the YbgF TPR domain and CTPR3Y3 leads to the formation of higher order oligomers both in the crystal and in solution. However, such open-ended self-association does not occur in full-length YbgF suggesting that the protein's N-terminal coiled-coil domain restricts further oligomerization. This interpretation is borne out in experiments where the coiled-coil domain of YbgF was engineered onto the N-terminus of CTPR3Y3 and shown to block self-association beyond trimerization. Our study lays the foundations for understanding the structural basis for TPR domain self-association and how such self-association can be regulated in TPR domain-containing proteins.

Coarse-Grained Simulation Studies of Peptide-Induced Pore Formation

We investigate the interactions between lipid bilayers and amphiphilic peptides using a solvent-free coarse-grained simulation technique. In our model, each lipid is represented by one hydrophilic and three hydrophobic beads. The amphiphilic peptide is modeled as a hydrophobic-hydrophilic cylinder with hydrophilic caps. We find that with increasing peptide-lipid attraction the preferred state of the peptide changes from desorbed, to adsorbed, to inserted. A single peptide with weak attraction binds on the bilayer surface, while one with strong attraction spontaneously inserts into the bilayer. We show how several peptides, which individually bind only to the bilayer surface, cooperatively insert. Furthermore, hydrophilic strips along the peptide cylinder induce the formation of multipeptide pores, whose size and morphology depend on the peptides’ overall hydrophilicity, the distribution of hydrophilic residues, and the peptide-peptide interactions. Strongly hydrophilic peptides insert less readily, but prove to be more destructive to bilayer integrity.

Structure and Dynamics of Model Pore Insertion into a Membrane

A cylindrical transmembrane molecule is constructed by linking hydrophobic sites selected from a coarse grain model. The resulting hollow tube assembly serves as a representation of a transmembrane channel, pore, or a carbon nanotube. The interactions of a coarse grain di-myristoyl-phosphatidyl-choline hydrated bilayer with both a purely hydrophobic tube and a tube with hydrophilic caps are studied. The hydrophobic tube rotates in the membrane and becomes blocked by lipid tails after a few tens of nanoseconds. The hydrophilic sites of the capped tube stabilize it by anchoring the tube in the lipid headgroup/water interfacial region of each membrane leaflet. The capped tube remains free of lipid tails. The capped tube spontaneously conducts coarse grain water sites; the free-energy profile of this process is calculated using three different methods and is compared to the barrier for water permeation through the lipid bilayer. Spontaneous tube insertion into an undisturbed lipid bilayer is also studied, which we reported briefly in a previous publication. The hydrophobic tube submerges into the membrane core in a carpetlike manner. The capped tube laterally fuses with the closest leaflet, and then, after plunging into the membrane interior, rotates to assume a transbilayer orientation. Two lipids become trapped at the end of the tube as it penetrates the membrane. The hydrophilic headgroups of these lipids associate with the lower tube cap and assist the tube in crossing the interior of the membrane. When the rotation is complete these lipids detach from the tube caps and fuse with the lower leaflet lipids.

Transmembrane Peptide-Induced Lipid Sorting and Mechanism of L α-to-Inverted Phase Transition Using Coarse-Grain Molecular Dynamics

Molecular dynamics results are presented for a coarse-grain model of 1,2-di-n-alkanoyl- sn-glycero-3-phosphocholine, water, and a capped cylindrical model of a transmembrane peptide. We first demonstrate that different alkanoyl-length lipids are miscible in the liquid-disordered lamellar ( L α ) phase. The transmembrane peptide is constructed of hydrophobic sites with hydrophilic caps. The hydrophobic length of the peptide is smaller than the hydrophobic thickness of a bilayer consisting of an equal mixture of long and short alkanoyl tail lipids. When incorporated into the membrane, a meniscus forms in the vicinity of the peptide and the surrounding area is enriched in the short lipid. The meniscus region draws water into it. In the regions that are depleted of water, the bilayers can fuse. The lipid headgroups then rearrange to solvate the newly formed water pores, resulting in an inverted phase. This mechanism appears to be a viable pathway for the experimentally observed L α -to-inverse hexagonal ( H II) peptide-induced phase transition.

Uptake and processing of glycosylated mycolates for presentation to CD1b-restricted T cells

Antigen presenting cells (APCs) expressing CD1b mediate the specific T cell recognition of mycobacterial lipid antigens. These lipid antigens require internalization by APCs prior to presentation, but the detailed mechanisms of uptake and intracellular processing are not known. Here we have examined several steps in the presentation of two related classes of CD1b-presented antigens, free and glycosylated mycolates. T cell recognition of glucose monomycolate (GMM) was blocked by agents that fix APC membranes or neutralize the pH of endosomes, indicating a requirement for GMM uptake into an acidic compartment prior to recognition. Different T cell lines responded to free mycolate or GMM without crossreactivity, yet both antigens were taken up by APCs at the same rate. This demonstrated that differential recognition of these antigens resulted from T cell specificity for their hydrophilic caps and that APCs were unable to interconvert these antigens by enzymatic or chemical deglycosylation or glycosylation. APCs were also unable to cleave mycobacterial trehalose dimycolate (TDM) at its most chemically labile linkages to yield antigenic free mycolates or GMM. Our results indicate that these mycolate-containing antigens are resistant to chemical or enzymatic cleavage by APCs, suggesting that molecular trimming is not a universal feature of lipid antigen processing.