[1-9-NαC]-Linusorb B3 (Cyclo-linopeptide A) dimethyl sulfoxide monosolvate.

Crystals of the dimethyl sulfoxide (DMSO) solvate of [1-9-NαC]-linusorb B3 (Cyclo-linopeptide A; CLP-A; CHNO·CHOS), a cyclic polypeptide were obtained following peptide extraction and purification from flaxseed oil. There are four intramolecular N-H⋯O hydrogen bonds. In the crystal, the mol-ecules are linked in chains along the axis by N-H⋯O hydrogen bonds.

Molecular Engineering as an Approach To Modulate Gene Delivery Efficiency of Peptide-Modified Gemini Surfactants.

The unique molecular structure confers the diquaternary ammonium gemini surfactants with enhanced nucleic acid complexation ability, bottom-up design flexibility, and relatively low cytotoxicity. To capitalize on their potential as gene delivery vectors, novel structural modifications should be explored. In this work, 22 novel peptide-modified gemini surfactants with various alkyl tails and peptide spacer modifications were evaluated.

The development of simple flow injection analysis tandem mass spectrometric methods for the cutaneous determination of peptide-modified cationic gemini surfactants used as gene delivery vectors.

Diquaternary ammonium gemini surfactants are a class of non-viral gene delivery vectors, primarily studied for their dermal applications. However, their biological fate has rarely been investigated. In this work, we developed simple flow injection analysis tandem mass spectrometric methods, (FIA)-MS/MS, to understand the fate and biodistribution of topically applied gemini surfactant-based therapeutics in an ex-vivo skin model.

Design and Evaluation of RGD-Modified Gemini Surfactant-Based Lipoplexes for Targeted Gene Therapy in Melanoma Model.

Purpose: We have developed and evaluated novel peptide-targeted gemini surfactant-based lipoplexes designed for melanoma gene therapy.

Methods: Integrin receptor targeting peptide, cyclic-arginylglycylaspartic acid (cRGD), was either chemically coupled to a gemini surfactant backbone or physically co-formulated with lipoplexes. Several formulations and transfection techniques were developed.

Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models.

Novel drug delivery systems are developed to improve the biological behavior of poorly soluble drugs and to improve therapeutic outcomes. In melanoma therapy, the goal is efficient drug delivery and mitigation of drug resistance. Melphalan (Mel), a currently used therapeutic agent for melanoma, requires solvent system for solubilization, leading to poor chemical stability.

The Development of Novel Nanodiamond Based MALDI Matrices for the Analysis of Small Organic Pharmaceuticals.

The utility of novel functionalized nanodiamonds (NDs) as matrices for matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) is described herein. MALDI-MS analysis of small organic compounds (<1000 Da) is typically complex because of interferences from numerous cluster ions formed when using conventional matrices. To expand the use of MALDI for the analysis of small molecules, novel matrices were designed by covalently linking conventional matrices (or a lysine moiety) to detonated NDs.

Di-Peptide-Modified Gemini Surfactants as Gene Delivery Vectors: Exploring the Role of the Alkyl Tail in Their Physicochemical Behavior and Biological Activity.

The aim of this work was to elucidate the structure-activity relationship of new peptide-modified gemini surfactant-based carriers. Glycyl-lysine modified gemini surfactants that differ in the length and degree of unsaturation of their alkyl tail were used to engineer DNA nano-assemblies. To probe the optimal nitrogen to phosphate (N/P) ratio in the presence of helper lipid, in vitro gene expression and cell toxicity measurements were carried out.

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application.

Purpose: Nanodiamonds (NDs) are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND) in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes.

Development of amino acid substituted gemini surfactant-based mucoadhesive gene delivery systems for potential use as noninvasive vaginal genetic vaccination.

Aim: Recently, we synthesized amino acid- and peptide-substituted gemini surfactants, 'biolipids' that exhibited high transfection efficiency in vitro. In this study, we developed these plasmid DNA and gemini surfactant lipid particles for noninvasive administration in vaginal cavity.

Material & Methods: Novel formulations of these gene delivery systems were prepared with poloxamer 407 to induce in situ gelling of the formulation and diethylene glycol monoethyl ether to improve their penetration across mucosal tissue.

Characterization of the host-guest complex of a curcumin analog with β-cyclodextrin and β-cyclodextrin-gemini surfactant and evaluation of its anticancer activity.

Background: Curcumin analogs, including the novel compound NC 2067, are potent cytotoxic agents that suffer from poor solubility, and hence, low bioavailability. Cyclodextrin-based carriers can be used to encapsulate such agents. In order to understand the interaction between the two molecules, the physicochemical properties of the host-guest complexes of NC 2067 with β-cyclodextrin (CD) or β-cyclodextrin-gemini surfactant (CDgemini surfactant) were investigated for the first time.

Multi-stage tandem mass spectrometric analysis of novel β-cyclodextrin-substituted and novel bis-pyridinium gemini surfactants designed as nanomedical drug delivery agents.

Rationale: This study aimed at evaluating the collision-induced dissociation tandem mass spectrometric (CID-MS/MS) fragmentation patterns of novel β-cyclodextrin-substituted- and bis-pyridinium gemini surfactants currently being explored as nanomaterial drug delivery agents. In the β-cyclodextrin-substituted gemini surfactants, a β-cyclodextrin ring is grafted onto an N,N-bis(dimethylalkyl)-α,ω-aminoalkane-diammonium moiety using variable succinyl linkers. In contrast, the bis-pyridinium gemini surfactants are based on a 1,1'-(1,1'-(ethane-1,2-diylbis(sulfanediyl))bis(alkane-2,1-diyl))dipyridinium template, defined by two symmetrical N-alkylpyridinium parts connected through a fixed ethane dithiol spacer.

Lysine-functionalized nanodiamonds: synthesis, physiochemical characterization, and nucleic acid binding studies.

Purpose: Detonation nanodiamonds (NDs) are carbon-based nanomaterials that, because of their size (4-5 nm), stable inert core, alterable surface chemistry, fluorescence, and biocompatibility, are emerging as bioimaging agents and promising tools for the delivery of biochemical molecules into cellular systems. However, diamond particles possess a strong propensity to aggregate in liquid formulation media, restricting their applicability in biomedical sciences. Here, the authors describe the covalent functionalization of NDs with lysine in an attempt to develop nanoparticles able to act as suitable nonviral vectors for transferring genetic materials across cellular membranes.

Design and evaluation of cyclodextrin-based delivery systems to incorporate poorly soluble curcumin analogs for the treatment of melanoma.

Various analogs of curcumin show high in vitro cytotoxic activity and are potential candidates for treating a deadly skin disease, melanoma. Due to the low solubility of the drugs, a new delivery agent, namely a cationic gemini surfactant-conjugated β-cyclodextrin, was designed to incorporate novel drug candidates of the 1,5-diaryl-3-oxo-1,4-pentadienyl family. Based on physicochemical parameters, such as particle size and zeta potential, a schematic model for the potential interaction of the drug with the delivery agent was developed.

Evaluation of cellular uptake and intracellular trafficking as determining factors of gene expression for amino acid-substituted gemini surfactant-based DNA nanoparticles.

Background: Gene transfer using non-viral vectors offers a non-immunogenic and safe method of gene delivery. Cellular uptake and intracellular trafficking of the nanoparticles can impact on the transfection efficiency of these vectors. Therefore, understanding the physicochemical properties that may influence the cellular uptake and the intracellular trafficking can aid the design of more efficient non-viral gene delivery systems.

Synthesis of palladacycles employing iminoisoindolines as monoanionic bidentate ligands.

A series of air- and moisture-stable iminoisoindoline-based palladacycles have been prepared in two operationally simple steps from commercially available reagents. para-Substituted N,N'-diphenyliminoisoindoline ligands are easily synthesized from phthalaldehyde and para-substituted anilines and further reaction of the iminoisoindoline ligands with Pd(OAc)(2) in dichloromethane at room temperature results in formation of six-membered [C,N] dinuclear cyclopalladated complexes with the general formula [(iminoisoindoline)Pd(micro-OAc)](2). The resulting palladacyclic complexes were tested as precatalysts in Heck and Suzuki coupling reactions.

Bis[2-phenyl-1-(phenyl-iminio)isoindo-line] di-μ-chlorido-bis-[dichloridopalladate(II)] benzene disolvate.

In the title compound, (C(20)H(17)N(2))(2)[Pd(2)Cl(6)]·2C(6)H(6), the dichloride-bridged [Pd(2)Cl(6)](2-) anion lies across an inversion center with each Pd(II) ion in a slightly distorted square-planar environment. In the crystal structure, two cations and an anion are connected via N-H⋯Cl hydrogen bonds between the NH groups of the iminioisoindoline cations and terminal Cl atoms of a hexa-chloridodipalladate(II) anion. The Pd-Cl distance of the terminal chloride engaged in hydrogen bonding is slightly longer than the Pd-Cl distance of the adjacent terminal chloride which is not involved in hydrogen bonding.

N-(2,6-Diisopropyl-phen-yl)formamide.

The title compound, C(13)H(19)NO, exhibits a non-planar structure in which the 2,6-diisopropyl-phenyl ring is tilted at a dihedral angle of 77.4 (1)° with respect to the formamide group. This is the largest dihedral angle known among structurally characterized formamides.