Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry.

Extracellular vesicles (EVs) are lipid bilayer structures released by all cells that mediate cell-to-cell communication via the transfer of bioactive cargo. Because of the natural origin of EVs, their efficient uptake by recipient cells, capacity to stabilize and transport biomolecules and their potential for cell/tissue targeting and preferential uptake by cancer cells, they have enormous potential for bioengineering into improved and targeted drug delivery systems. In this work, we investigated the use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a tool to measure the loading of platinum-based chemotherapeutic agents.

Water-Soluble Truncated Fatty Acid-Porphyrin Conjugates Provide Photo-Sensitizer Activity for Photodynamic Therapy in Malignant Mesothelioma.

Clinical trials evaluating intrapleural photodynamic therapy (PDT) are ongoing for mesothelioma. Several issues still hinder the development of PDT, such as those related to the inherent properties of photosensitizers. Herein, we report the synthesis, photophysical, and photobiological properties of three porphyrin-based photosensitizers conjugated to truncated fatty acids (C5SHU to C7SHU).

Photocatalytic Reduction of CO to CO in Aqueous Solution under Red-Light Irradiation by a Zn-Porphyrin-Sensitized Mn(I) Catalyst.

This work demonstrates photocatalytic CO reduction by a noble-metal-free photosensitizer-catalyst system in aqueous solution under red-light irradiation. A water-soluble Mn(I) tricarbonyl diimine complex, [MnBr(4,4'-{EtOPCH}-2,2'-bipyridyl)(CO)] (), has been fully characterized, including single-crystal X-ray crystallography, and shown to reduce CO to CO following photosensitization by tetra(-methyl-4-pyridyl)porphyrin Zn(II) tetrachloride [Zn(TMPyP)]Cl () under 625 nm irradiation. This is the first example of employed as a photosensitizer for CO reduction.

Optimization of gold nanoparticle-based real-time colorimetric assay of dipeptidyl peptidase IV activity.

Dipeptidyl peptidase IV (DPP-IV also referred to as CD-26) is a serine protease enzyme with remarkable diagnostic and prognostic value in a variety of health and disease conditions. Herein, we describe a simple and real-time colorimetric assay for DPP-IV/CD-26 activity based on the aggregation of gold nanoparticles (AuNPs) functionalized with the peptide substrates: Gly-Pro-Asp-Cys (GPDC) or Val-Pro-ethylene diamine-Asp-Cys (VP-ED-DC). Cleavage of the substrates by DPP-IV resulted in aggregation of the AuNPs with accompanying color change in the solution from red to blue that was monitored using either a UV-visible spectrophotometer or by the naked eye.

Correction: Modulating the electron-transfer properties of a mixed-valence system through host-guest chemistry.

[This corrects the article DOI: 10.1039/C4SC02799J.].

Virtual screening for high affinity guests for synthetic supramolecular receptors.

The protein/ligand docking software GOLD, which was originally developed for drug discovery, has been used in a virtual screen to identify small molecules that bind with extremely high affinities ( ≈ 10 M) in the cavity of a cubic coordination cage in water. A scoring function was developed using known guests as a training set and modified by introducing an additional term to take account of loss of guest flexibility on binding. This scoring function was then used in GOLD to successfully identify 15 new guests and accurately predict the binding constants.

Modulating the electron-transfer properties of a mixed-valence system through host-guest chemistry.

Metal directed self-assembly has become a much-studied route towards complex molecular architectures. Although studies on mixed valence, MV, systems accessible through this approach are almost non-existent, the potential applications of such systems are very exciting as MV states provide the basis of a number of molecular-scale devices, including single electron wires and switches. Furthermore, while many novel hosts for guest ions and molecules have been developed through metal directed self-assembly, as these products tend to be kinetically labile, very few electrochemical studies have been reported.

pH-dependent binding of guests in the cavity of a polyhedral coordination cage: reversible uptake and release of drug molecules.

A range of organic molecules with acidic or basic groups exhibit strong pH-dependent binding inside the cavity of a polyhedral coordination cage. Guest binding in aqueous solution is dominated by a hydrophobic contribution which is compensated by stronger solvation when the guests become cationic (by protonation) or anionic (by deprotonation). The Parkinson's drug 1-amino-adamantane ('amantadine') binds with an association constant of 10 M in the neutral form (pH greater than 11), but the stability of the complex is reduced by three orders of magnitude when the guest is protonated at lower pH.

Mapping the internal recognition surface of an octanuclear coordination cage using guest libraries.

Size and shape criteria for guest binding inside the cavity of an octanuclear cubic coordination cage in water have been established using a new fluorescence displacement assay to quantify guest binding. For aliphatic cyclic ketones of increasing size (from C5 to C11), there is a linear relationship between ΔG for guest binding and the guest's surface area: the change in ΔG for binding is 0.3 kJ mol(-1) Å(-2), corresponding to 5 kJ mol(-1) for each additional CH2 group in the guest, in good agreement with expectations based on hydrophobic desolvation.

Relationship between chemical structure and supramolecular effective molarity for formation of intramolecular H-bonds.

Effective molarity (EM) is a key parameter that determines the efficiency of a range of supramolecular phenomena from the folding of macromolecules to multivalent ligand binding. Coordination complexes formed between zinc porphyrins equipped H-bond donor sites and pyridine ligands equipped with H-bond acceptor sites have allowed systematic quantification of EM values for the formation of intramolecular H-bonds in 240 different systems. The results provide insights into the relationship of EM to supramolecular architecture, H-bond strength, and solvent.

Quantification of the effect of conformational restriction on supramolecular effective molarities.

The association constants for a family of 96 closely related zinc porphyrin-pyridine ligand complexes have been measured in two different solvents, toluene and 1,1,2,2-tetrachloroethane (TCE). The zinc porphyrin receptors are equipped with phenol side arms, which can form intramolecular H-bonds with ester or amide side arms on the pyridine ligands. These association constants were used to construct 64 chemical double mutant cycles, which measure the free energy contributions of intramolecular H-bonding interactions to the overall stability of the complexes.

Shape-, size-, and functional group-selective binding of small organic guests in a paramagnetic coordination cage.

The host-guest chemistry of the octanuclear cubic coordination cage [Co(8)L(12)](16+) (where L is a bridging ligand containing two chelating pyrazolyl-pyridine units connected to a central naphthalene-1,5-diyl spacer via methylene "hinges") has been investigated in detail by (1)H NMR spectroscopy. The cage encloses a cavity of volume of ca. 400 Å(3), which is accessible through 4 Å diameter portals in the centers of the cube faces.

Steric desolation enhances the effective molarities of intramolecular H-bonding interactions.

Free energy contributions due to intramolecular phosphonate diester-phenol H-bonds have been measured for 20 different supramolecular architectures in cyclohexanone solution. High throughput UV/Vis titrations were used in combination with chemical double mutant cycles to dissect out the contributions of different functional group interactions to the stabilities of over 100 different zinc porphyrin-pyridine ligand complexes. These complexes have previously been characterised in toluene and in 1,1,2,2-tetrachloroethane (TCE) solution.

Selective guest recognition by a self-assembled paramagnetic cage complex.

A cubic cage complex assembled from twelve bis-bidentate ligands and eight Co(II) ions provides a cavity that selectively recognises and binds coumarin in MeCN solution. The cage portals are large enough to allow guest exchange, but small enough to provide a kinetic trap; the cage paramagnetism facilitates detailed NMR analysis.

Influence of H-bond strength on chelate cooperativity.

Intermolecular complexes formed between metalloporphyrins and pyridine ligands equipped with multiple H-bond donors and acceptors have been used to measure the free energy contributions due to intramolecular ether-phenol H-bonding in the 24 different supramolecular architectures using chemical double mutant cycles in toluene. The ether-phenol interactions are relatively weak, and there are significant populations of partially bound states where between zero and four intramolecular H-bonds are made in addition to the porphyrin-ligand coordination interaction. The complexes were analyzed as ensembles of partially bound states to determine the effective molarities for the intramolecular interactions by comparison with the corresponding intermolecular ether-phenol H-bonds.

Dissection of complex molecular recognition interfaces.

The synthesis of a family of zinc porphyrins and pyridine ligands equipped with peripheral H-bonding functionality has provided access to a wide range of closely related supramolecular complexes featuring between zero and four intramolecular H-bonds. An automated UV/vis titration system was used to characterize 120 different complexes, and these data were used to construct a large of number of different chemical double mutant cycles to quantify the intramolecular H-bonding interactions. The results probe the quantitative structure-activity relationship that governs cooperativity in the assembly of complex molecular recognition interfaces.

A simple network of synthetic replicators can perform the logical OR operation.

A small network of synthetic replicators is capable of responding to instructional inputs such that the output of the network is an excess of one of the replicators whenever the input contains either or both of the replicators, mirroring the OR boolean logic operation.

Chemical double mutant cycles for the quantification of cooperativity in H-bonded complexes.

Chemical double mutant cycles have been used in conjunction with new H-bonding motifs for the quantification of chelate cooperativity in multiply H-bonded complexes. The double mutant cycle approach specifically deals with the effects of substituents, secondary interactions, and allosteric cooperativity on the free energy contributions from individual H-bond sites and allows dissection of the free energy contribution due to chelate cooperativity associated with the formation of intramolecular noncovalent interactions. Two different doubly H-bonded motifs were investigated in carbon tetrachloride, chloroform, 1,1,2,2-tetrachloroethane, and cyclohexane, and the results were similar in all cases, with effective molarities of 3-33 M for formation of intramolecular H-bonds.

Cooperativity in multiply H-bonded complexes.

The free energy of complexation of supramolecular complexes containing phenol-carbamate H-bonds is an additive function of the number of H-bonds, with a constant increment of 6 kJ mol(-1) per interaction in carbon tetrachloride.

Evidence for partially bound states in cooperative molecular recognition interfaces.

A zinc porphyrin equipped with four amide H-bonding sites provides a rigid molecular receptor for the study of cooperative multipoint binding interactions. The interaction of this receptor with a variety of pyridine ligands bearing zero, one, and two H-bonding sites has been studied using UV/vis absorption, (1)H and (31)P NMR spectroscopy, and isothermal titration calorimetry in five different solvents. The results are analyzed in terms of a bound state that populates an ensemble of different complexes in which zero, one, or two of the potential H-bond interactions are formed.

Target-driven selection in a dynamic nitrone library.

Nitrones undergo dynamic exchange in chloroform at room temperature through two mechanisms-hydrolysis and recombination or hydroxylamine addition/elimination; this dynamic exchange is harnessed to select a nitrone-based bis(amidopyridine) receptor for diacids from a group of four nitrones through its binding to a glutaric acid-based target.

Probing the limits of rate acceleration mediated by hydrogen bonds.

[Structure: see text] A simple receptor and substrate are used to probe the relationship between transition-state charge and the level of rate acceleration that can be created by stabilizing the transition state through hydrogen bonding. Pericyclic reactions are accelerated less than 2-fold by the receptor, whereas a conjugate addition reaction is accelerated more than 30-fold. Therefore, substrate polarization by hydrogen bonding would only appear to be effective for reactions that generate significant charge at the transition state.

Controlling a recognition-mediated reaction using a pH switch.

The selective recognition-mediated reaction between a nitrone bearing a urea recognition site and a maleimide bearing a proton switchable recognition site can be turned 'on' and 'off' by the addition of base and acid respectively.