Pyridyl-, bipyridyl-, and terpyridyl-functionalised azamacrocycles

Abstract

A series of azamacrocycles which have been N-functionalised with pendent pyridylmethyl-(pyCH₂-), bipyridylmethyl-(bipyCH₂-) and terpyridylmethyl- (terpyCH₂-) arms have been synthesised and characterised, and some of their coordination chemistry with transition metal ions is reported. By attaching the pendent-arms at the 5- rather than the 6-position of the py, bipy and terpy, new ligands are generated which can be used to form polynuclear metal complexes in a controlled and systematic fashion. Fluorescent pH and transition metal ion sensors have been developed by reacting the azamacrocyclic N-pendent bipyCH₂ arm(s) with cis-[Ru(bipy)₂Cl₂], to give macrocycles with up to four attached [Ru(bipy)₃]²⁺ groups. That based on 1,4,7-triazacyclononane (9N3), with three attached [Ru(bipy)₃]²⁺ groups, has a first photo excited state pK_a of 7.1, and is a useful fluorescent sensor for physiological pH at below micromolar concentrations. The analogous derivative of cyclam (1,4,8,11-tetraazacyclotetradecane) carrying four [Ru(bipy)₃]²⁺ groups has a first photo excited state pK_a of 5.7, allowing kinetic and thermodynamic fluorescence studies of metal ion uptake by an azamacrocycle at neutral pH without complications from protonated species. A pre-organised hexadentate tris(2,2′-bipyridyl) chelating ligand, 1,4,7-tris(2′,2″-bipyridyl-5′-ylmethyl)-1,4,7-triazacyclononane (L) has been developed, and crystal structures of mononuclear complexes [M(LH)]³⁺ (M = Ru, Cu) are reported. In [M(LH)]³⁺ the azamacrocyclic N-atoms are non-coordinating to M, but have a very high affinity for a single proton trapped in the macrocyclic cavity. An analogous and potentially nonadentate ligand has been developed based on 9N3 with three N-pendent terpyCH₂-arms.     

QMX: A versatile environment for hybrid calculations applied to the grafting of Al2Cl3Me3 on a silica surface

We present a new software to easily perform QM:MM and QM:QM' calculations called QMX. It follows the subtraction scheme and it is implemented in the Atomic Simulation Environment (ASE). Special attention is paid to couple molecular calculations with periodic boundaries approaches. QMX inherits the flexibility and versatility of the ASE package: any combination of methods namely force field, semiempirical, first principle, and ab initio, can be used as hybrid potential energy surface (PES). Its ease of use is demonstrated by considering the adsorption of Al₂Cl₃Me₃ on silica surface and by combining different levels of theory (from standard DFT to MP2 calculations) for the so‐called High Level cluster with standard PW91 density functional theory calculations for the Low Level environment. It is shown that the High Level cluster must contain the silanol group close to the aluminum atoms. The bridging adsorption is favored by 58 kJ mol^?1 at the MP2:PW91 level with respect to the terminal position. Using large clusters at the MP2:PW91 level, it is shown that PW91 calculations are sufficient for structure optimization but that embedded methods are required for accurate energy profiles. © 2013 Wiley Periodicals, Inc.     

Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb

Background  

New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ). These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB), ending their migration in the glomerular layer (GLL) and the granule cell layer (GCL) of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtype-specific markers is not known.     

Allocating operating funding in the public sector and the newsvendor problem

Public sector managers, particularly those at the highest level of government, tend to view lapsed (or unused) funds at the end of a fiscal year as a consequence of poor management and/or inadequate financial controls. The aim of this paper is to challenge this view. We show that the planning environment in the public sector is in essence the classical Newsvendor Problem. This simple model argues that lapsed funds are a direct consequence of a manager doing his job properly; that is, lapsed funds occur from time to time when a manager is maximizing value for the organization. An extension of the model shows that allowing low-value year-end spending has an undesirable effect on the value of spending during the year and this suggests a role for a strong audit function for year-end spending.     

Longitudinal 3D Blood Flow Distribution Provided by Diffuse Correlation Tomography during Bone Healing in a Murine Fracture Model

Noninvasive monitoring of vascularization can potentially diagnose impaired bone healing earlier than current radiographic methods. In this study, a noncontact diffuse correlation tomography (DCT) technique was employed to measure longitudinal blood flow changes during bone healing in a murine femoral fracture model. The three-dimensional distribution of the relative blood flow was quantified from one day pre-fracture to 48 days post-fracture. For three mice, frequent DCT measurements were performed every other day for one week after fracture, and then weekly thereafter. A decrease in blood flow was observed in the bone fracture region at one day post-fracture, followed by a monotonic increase in blood flow beyond the pre-injury baseline until five to seven days post-fracture. For the remaining 12 mice, only weekly DCT measurements were performed. Data collected on a weekly basis show the blood flow for most mice was elevated above baseline during the first two post-fracture weeks, followed by a subsequent decrease. Torsional strength of the excised femurs was measured for all 15 mice after 7 weeks of healing. A metric based on the early blood flow changes shows a statistically significant difference between the high strength group and the low strength group.     

Optimization of Biocompatibility for a Hydrophilic Biological Molecule Encapsulation System

Despite considerable advances in recent years, challenges in delivery and storage of biological drugs persist and may delay or prohibit their clinical application. Though nanoparticle-based approaches for small molecule drug encapsulation are mature, encapsulation of proteins remains problematic due to destabilization of the protein. Reverse micelles composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) in low-viscosity alkanes have been shown to preserve the structure and stability of a wide range of biological macromolecules. Here, we present a first step on developing this system as a future platform for storage and delivery of biological drugs by replacing the non-biocompatible alkane solvent with solvents currently used in small molecule delivery systems. Using a novel screening approach, we performed a comprehensive evaluation of the 10MAG/LDAO system using two preparation methods across seven biocompatible solvents with analysis of toxicity and encapsulation efficiency for each solvent. By using an inexpensive hydrophilic small molecule to test a wide range of conditions, we identify optimal solvent properties for further development. We validate the predictions from this screen with preliminary protein encapsulation tests. The insight provided lays the foundation for further development of this system toward long-term room-temperature storage of biologics or toward water-in-oil-in-water biologic delivery systems.     

Multi-criteria logistics modeling for military humanitarian assistance and disaster relief aerial delivery operations

Given that it is not always feasible to reach an affected area via land or sea within the first week following a natural disaster, aerial delivery provides the primary means to rapidly supply the affected population. Further, it is often the case that high density delivery of humanitarian aid supplies are taken over by non-friendly groups within the affected population. By using direct airdrop systems to deliver large quantities of individually wrapped food and water items, dispersion among the affected disaster relief population will occur more quickly. In this paper, we proffer a multiple criteria decision analysis (MCDA) framework to optimize the military humanitarian assistance/disaster relief (HA/DR) aerial delivery supply chain network. The model uses stochastic, mixed-integer, weighted goal programming to optimize network design, logistics costs, staging locations, procurement amounts, and inventory levels. The MCDA framework enables decision-makers to explore the trade-offs between military HA/DR aerial delivery supply chain efficiency and responsiveness, while optimizing across a wide range of real-world, probabilistic scenarios to account for the inherent uncertainty in the location of global humanitarian disasters as well as the amount of demand to be met.     

Fluorescent 1,10-phenanthroline-containing oligonucleotides distinguish between perfect and mismatched base pairing

[structure: see text] A fluorescent deoxyuridine analogue is sensitive to the polarity of its environment and exhibits a distinct emission profile in single- vs double-stranded oligonucleotides. Emission-monitored denaturation curves of internally modified dU(phen) duplexes are characteristic of the base opposite dU(phen) and distinguish between perfect and mismatched complementary oligonucleotides.     

Probing acoustic nonlinearity on lengths scales comparable to material grain dimensions

The focus of this presentation is to describe our efforts at laser generation of high frequency surface acoustic waves and detection of the nonlinear contribution in the acoustic near-field of the source. Narrow band acoustic generation is accomplished by interfering two pulsed laser beams at the surface of the sample. A Michelson interferometer, that incorporates a high power microscope objective, is used to detect the acoustic disturbance. Detection near the source combined with high frequency generation (approximately 0.1 GHz) facilitates investigation of fundamental processes of harmonic generation on length scales comparable to grain size dimensions.