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This essay aims to analyze the various scenarios in economic activities and the relationship that exists between the Public Sector and the Private Sector, by proposing to work in a coordinated manner on an investment project with an environmental focus. For this case, about a decrease in air pollution in a part of the Guadalajara Metropolitan Area (Jalisco, Mexico). Based on the information seen in the Seminar “Prospective, complex thinking and transdiscipline”, and as part of the indicated activities, was? didactic material that exemplifies the development of concepts, methodology and economic and financial analysis tools used in the subject of Formulation and Evaluation of Projects taught in the Economics Degree of the University of Guadalajara. The logical framework methodology is used, in which the relationship between the Public Sector and the Private Sector is articulated, as links that occur systematically in a complex environment, such as air pollution in cities and that it affects the public health of the population.

We report the microwave-assisted synthesis of binary doped optical-magnetic up/downconverting NaGdF4:RE and iron oxide/SiO2/NaGdF4:RE nanoparticles. The morphological characteristics were finely tuned from elongated rod-shaped to ovoidal nanoparticles. The (Yb, and Er) activated particles provided an excellent up/down conversion luminescence emission in the green and mid-infrared region under excitation of 980 nm, whereas the (Ce, and Eu) activated systems exhibited a strong red emission via the Gd3+ sublattice upon excitation in the UV region. The magnetic hysteresis at 300 K for β-NaGdF4:RE showed typical signatures of a paramagnetic system, whereas iron oxide/SiO2/β-NaGdF4:RE exhibited superparamagnetic behavior along with a Curie-like component. The luminescence quenching effects induced by the presence of iron oxide phase have been validated through comparing the emission/lifetime decay curves. In addition to the excellent optical and magnetic properties, these materials show remarkably high longitudal and transverse relaxivity values (for Fe and Gd) and thus are potential candidates for T1 and T2-weighted bioimaging.

The development of stimuli-responsive small molecules for probing biologically active antioxidants such as glutathione (GSH) has important ramifications in the detection of oxidative stress. An ideal sensor for biological applications should exhibit sufficient sensitivity and selectivity for detection at physiological concentrations and be reversible to allow continuous and dynamic monitoring of antioxidant levels. Designing a suitable sensor thus requires a detailed understanding of activation properties and mechanism of action. In this work, we report a new set of GSH-responsive spiropyrans and demonstrate how changes in the electronic structure of spiropyrans influence GSH sensing with high specificity versus other structurally similar and biologically relevant redox-active molecules. The sensitivity, selectivity, kinetics, binding constant, and reversibility of GSH-responsive-substituted spiropyrans were investigated using UV-vis spectroscopy and laser irradiation experiments. Detailed studies of the mechanism of interaction between spiropyrans with GSH were investigated using NMR spectroscopy. Understanding how electronic effects impact the sensing ability of spiropyrans toward antioxidants and elucidating the mechanism of the spiropyran-GSH interaction will facilitate the design of more effective sensors for detection of antioxidants in vivo.

The metal-binding capabilities of the spiropyran family of molecular switches have been explored for several purposes from sensing to optical circuits. Metal-selective sensing has been of great interest for applications ranging from environmental assays to industrial quality control, but sensitive metal detection for field-based assays has been elusive. In this work, we demonstrate colorimetric copper sensing at low micromolar levels. Dimethylamine-functionalized spiropyran (SP1) was synthesized and its metal-sensing properties were investigated using UV-vis spectrophotometry. The formation of a metal complex between SP1 and Cu2+ was associated with a color change that can be observed by the naked eye as low as ≈6 μM and the limit of detection was found to be 0.11 μM via UV-vis spectrometry. Colorimetric data showed linearity of response in a physiologically relevant range (0-20 μM Cu2+) with high selectivity for Cu2+ ions over biologically and environmentally relevant metals such as Na+, K+, Mn2+, Ca2+, Zn2+, Co2+, Mg2+, Ni2+, Fe3+, Cd2+, and Pb2+. Since the color change accompanying SP1-Cu2+ complex formation could be detected at low micromolar concentrations, SP1 could be viable for field testing of trace Cu2+ ions.

Alcoholic beverages have a complex chemistry that can be influenced by their alcoholic content, origin, fermentation process, additives, and contaminants. The complex composition of these beverages leave them susceptible to fraud, potentially compromising their authenticity, quality, and market value, thus increasing risks to consumers’ health. In recent years, intensive studies have been carried out on alcoholic beverages using different analytical techniques to evaluate the authenticity, variety, age, and fermentation processes that were used. Among these techniques, NMR-based metabolomics holds promise in profiling the chemistry of alcoholic beverages, especially in Asia where metabolomics studies on alcoholic beverages remain limited.

Light-activated sensors are of great interest for biological applications but are limited by the depth of penetration of light. We have been interested in transducing light activation to a magnetic signal that can be detected through noninvasive imaging by magnetic resonance imaging (MRI). We have previously developed agents incorporating spiropyran derivatives as the sensing moiety and characterized features that influence photoswitching; however, we found the MRI response to be unpredictable. In this work, we delve deeper into the potential mechanisms for the observed MRI responses in an effort to better understand the structural effects on controlling magnetic properties. A series of light-activatable MRI contrast agents were synthesized and characterized to assess the effect of spiropyran positioning on contrast agent functions and properties. These compounds are based on the same spiropyran skeleton, also named 1',3',3'-trimethyl-6-nitrospiro[chromene-2,2-indoline], which is linked with an MRI contrast agent, gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7-triacetate (DO3A). We investigated the photo-to-magnetic conversion properties of these novel compounds by adjusting linker lengths over a range from three to seven methylene groups. The primary results indicated that the contrast agent with a five-carbon linker (25) showed the highest light-sensing ability after irradiation with visible light. The results will aid in the design of future spiropyran-based MRI sensors.

Summary The flight muscles of Drosophila are highly enriched with mitochondria, but the mechanism by which mitochondrial complex I (CI) is assembled in this tissue has not been described. We report the mechanism of CI biogenesis in Drosophila flight muscles and show that it proceeds via the formation of ∼315, ∼550, and ∼815 kDa CI assembly intermediates. Additionally, we define specific roles for several CI subunits in the assembly process. In particular, we show that dNDUFS5 is required for converting an ∼700 kDa transient CI assembly intermediate into the ∼815 kDa assembly intermediate. Importantly, incorporation of dNDUFS5 into CI is necessary to stabilize or promote incorporation of dNDUFA10 into the complex. Our findings highlight the potential of studies of CI biogenesis in Drosophila to uncover the mechanism of CI assembly in vivo and establish Drosophila as a suitable model organism and resource for addressing questions relevant to CI biogenesis in humans.

Hybrid imaging is an emerging technology that typically fuses a combination of high-sensitivity, nuclear imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT), with high-resolution, anatomical imaging using computed tomography (CT) or magnetic resonance imaging (MRI). CT was the first partner in hybrid imaging systems and modern interest has focused on development of MRI hybrids. To fully exploit the benefits of hybrid imaging technology, researchers have been investigating the use of radiolabeled and paramagnetic, nanoparticle-based probes to allow simultaneous imaging with PET/SPECT and MRI for a variety of applications including targeted tumor imaging, stem cell tracking, and monitoring of response to therapy. This chapter provides an overview of unique designs for nanoparticle-based SPECT/MRI and PET/MRI probes, and their imaging applications, reported in the period of 2010–2015.

The influence of albumin on the efficacy of a Eu(2+)-containing complex capable of interacting with human serum albumin (HSA) was investigated at different field strengths (1.4, 3, 7, 9.4, and 11.7 T). Relaxometric measurements indicated that the presence of albumin at higher field strengths (3 T) did not result in an increase in the relaxivity of the Eu(2+) complex, but a relaxation enhancement of 171 ± 11% was observed at 1.4 T. Titration experiments using different percentages (2, 4.5, 6, 10, 15, and 25% w/v) of HSA and variable-temperature (17)O NMR measurements were performed to understand the effect of albumin on the molecular properties of the biphenyl-functionalized Eu(2+) complex that are relevant to magnetic resonance imaging.

Recent advances in the coordination chemistry of Eu(2+) are reviewed. Common synthetic routes for generating discrete Eu(2+)-containing complexes reported since 2000 are summarized, followed by a description of the reactivity of these complexes and their applications in reduction chemistry, polymerization, luminescence, and as contrast agents for magnetic resonance imaging. Rapid development of the coordination chemistry of Eu(2+) has led to an upsurge in the utilization of Eu(2+)-containing complexes in synthetic chemistry, materials science, and medicine.

The kinetic stabilities and relaxivities of a series of Eu(2+)-containing cryptates have been investigated. Transmetallation studies that monitored the change in the longitudinal relaxation rate of water protons in the presence of Ca(2+), Mg(2+), and Zn(2+) demonstrated that cryptate structure influences stability, and two of the cryptates studied were inert to transmetallation in the presence of these endogenous ions. The efficacy of these cryptates was determined at different magnetic field strengths, temperatures, and pH values. Cryptate relaxivity was found to be higher at ultra-high field strengths (7 and 9.4 T) relative to clinically relevant field strengths (1.4 and 3 T), but the efficiency of these cryptates decreased as temperature increased. In addition, variation in pH did not yield significant changes in the efficacy of the cryptates. These studies establish a foundation of important properties that are necessary to develop effective positive contrast agents for magnetic resonance imaging from Eu(2+)-containing cryptates.

Receptor for advanced glycation end product (RAGE)-dependent signaling has been implicated in ischemia/reperfusion injury in the heart, lung, liver, and brain. Because macrophages contribute to vascular perturbation and tissue injury in hypoxic settings, we tested the hypothesis that RAGE regulates early growth response-1 (Egr-1) expression in hypoxia-exposed macrophages. Molecular analysis, including silencing of RAGE, or blockade of RAGE with sRAGE (the extracellular ligand-binding domain of RAGE), anti-RAGE IgG, or anti-AGE IgG in THP-1 cells, and genetic deletion of RAGE in peritoneal macrophages, revealed that hypoxia-induced up-regulation of Egr-1 is mediated by RAGE signaling. In addition, the observation of increased cellular release of RAGE ligand AGEs in hypoxic THP-1 cells suggests that recruitment of RAGE in hypoxia is stimulated by rapid production of RAGE ligands in this setting. Finally, we show that mDia-1, previously shown to interact with the RAGE cytoplasmic domain, is essential for hypoxia-stimulated regulation of Egr-1, at least in part through protein kinase C betaII, ERK1/2, and c-Jun NH(2)-terminal kinase signaling triggered by RAGE ligands. Our findings highlight a novel mechanism by which an extracellular signal initiated by RAGE ligand AGEs regulates Egr-1 in a manner requiring mDia-1.

Endothelin 3 (Edn3) encodes a ligand important to developing neural crest cells and is allelic to the spontaneous mouse mutation occurring at the lethal spotting (ls) locus. Edn3(ls/ls) mutants exhibit a spotted phenotype due to reduced numbers of neural crest-derived melanocyte precursors in the skin. In this study, we show that when Edn3 is driven by the keratin 5 promoter and thereby placed proximal to melanocyte lineage cells, adult mice manifest pigmented skin harboring dermal melanocytes. Using a tetracycline inducible system, we show that the postnatal expression of Edn3 is required to maintain these dermal melanocytes, and that early expression of the Edn3 transgene is important to the onset of the hyperpigmentation phenotype. Crosses into Edn3(ls/ls) mutants demonstrate that the Edn3 transgene expression does not fully compensate for the endogenous expression pattern. Crosses into tyrosine kinase receptor Kit(Wv) mutants indicate that Edn3 can partially compensate for Kit's role in early development. Crosses into A(y) mutant mice considerably darkened their yellow coat color suggesting a previously unreported role for endothelin signaling in pigment switching. These results demonstrate that exogenous Edn3 affects both precursors and differentiated melanocytes, leading to a phenotype with characteristics similar to the human skin condition dermal melanocytosis.

In this work we synthesize molecular switches that are responsive to cysteine, homocysteine, and glutathione; three redox systems that make up the majority of the body’s antioxidant defenses. Synthesized spiropyran isomers with conjugation-ready linkages showed good selectivity of response to these major antioxidant thiols over nucleophilic amino acids; however the position of the linking group can affect selectivity and reversibility of the switching response. An isomer with selectivity for cysteine against GSH and Hcy was identified.

The integration of PET and MRI modalities into a single hybrid imaging system has been demonstrated to synergistically compensate for the limitations of each modality, with the potential to enhance diagnostic accuracy and improve development of therapeutics. To take advantage of the progress of the hybrid PET/MRI hardware, nanoparticle-based probes are being developed for multimodal applications. In this paper, recent advances in the development of nanoparticle-based, multimodal PET/MRI probes are reviewed. Common MRI contrast agents, PET tracers and chelators and surface functionality that comprised PET/MRI nanoprobes reported in the last 10 years are summarized, followed by a description of the physical properties of these probes and their imaging applications.

No discussion of challenges for chemistry in molecular imaging would be complete without addressing the elephant in the room—which is that the purest of chemical compounds needs to interact with a biological system in a manner that does not perturb normal biology while still providing efficacious feedback to assist in diagnosis of disease. In the past decade, magnetic resonance imaging (MRI) agents long considered inert have produced adverse effects in certain patient populations under certain treatment regimens. More recently, inert blood pool agents have been found to deposit in the brain. Release of free metal is often suspected as the culprit but that hypothesis has yet to be validated. In addition, even innocuous agents can cause painful side effects during injection in some patients. In this brief review, we summarize known biological effects for gadolinium- and iron-based MRI contrast agents, and discuss some of the potential mechanisms for the observed biological effects, including the potential role of phosphorus imbalance, related to kidney disease or cancer, in destabilizing gadolinium-based chelates and precipitating free gadolinium. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

Recent advances in the coordination chemistry of Eu2+ are reviewed. Common synthetic routes for generating discrete Eu2+-containing complexes reported since 2000 are summarized, followed by a description of the reactivity of these complexes and their applications in reduction chemistry, polymerization, luminescence, and as contrast agents for magnetic resonance imaging. Rapid development of the coordination chemistry of Eu2+ has led to an upsurge in the utilization of Eu2+-containing complexes in synthetic chemistry, materials science, and medicine.

The relaxivity (contrast-enhancing ability) of Eu(II)-containing cryptates was found to be better than a clinically approved Gd(III)-based agent at 7 T. These cryptates are among a few examples of paramagnetic substances that show an increase in longitudinal relaxivity, r(1), at ultra-high field strength relative to lower field strengths.

Polyaminopolycarboxylate-based ligands are commonly used to chelate lanthanide ions, and the resulting complexes are useful as contrast agents for magnetic resonance imaging (MRI). Many commercially available ligands are especially useful because they contain functional groups that allow for fast, high-purity, and high-yielding conjugation to macromolecules and biomolecules via amine-reactive activated esters and isothiocyanate groups or thiol-reactive maleimides. While metalation of these ligands is considered common knowledge in the field of bioconjugation chemistry, subtle differences in metalation procedures must be taken into account when selecting metal starting materials. Furthermore, multiple options for purification and characterization exist, and selection of the most effective procedure partially depends on the selection of starting materials. These subtle differences are often neglected in published protocols. Here, our goal is to demonstrate common methods for metalation, purification, and characterization of lanthanide complexes that can be used as contrast agents for MRI (Figure 1). We expect that this publication will enable biomedical scientists to incorporate lanthanide complexation reactions into their repertoire of commonly used reactions by easing the selection of starting materials and purification methods.

The magnetic and optical properties of the divalent state of europium make this ion extremely attractive for use in materials,[1] catalysis,[2] luminescence,[3] magnetic,[4] and diagnostic-medical applications. A major hindrance to the use of EuII in many of these applications is the extreme propensity of the ion to oxidize to EuIII, especially in aqueous solution. Research efforts aimed at increasing the stability of aqueous EuII have yielded little success:[6,7] even the most stable aqueous EuII complex reported (4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane europium(II), 1-Eu) is not stable enough in aqueous solution for practical use.[8,9] Our research group has generated EuII complexes in aqueous solution, and here we report the most oxidatively-stable aqueous EuII complexes known. Our strategy for favoring EuII over EuIII in aqueous solution involves the synthesis and use of ligands that would preferentially coordinate to large, soft, electron-rich metals like EuII. The template for our ligand design was cryptand 1 because 1-Eu is the most oxidatively-stable, aqueous EuII complex previously reported.[8] The stability of 1-Eu is partially due to the better size match of the cavity of cryptand 1 (1.4 A) to the EuII ion (1.25 A) relative to the EuIII ion (1.07 A).[10] We hypothesized that further oxidative stabilization could be achieved by modifying the structure of cryptand 1 using four principles of coordination chemistry to stabilize electron-rich metals.[6,11] Specifically, our goals were 1) to increase the steric bulk surrounding cryptand 1 to minimize interactions between EuII and its environment; 2) to reduce the Lewis basicity of cryptand 1 to favor the electron-rich EuII over EuIII; 3) to change the cavity size of the cryptand to match the size of the EuII ion preferentially; and 4) to modify the hard–soft, acid–base (HSAB) properties of cryptand 1 to coordinate EuII over EuIII. To implement these strategies, we studied cryptands 1–6 (Scheme 1). Scheme 1 Ligands used to observe trends in oxidative stability of aqueous EuII. To increase the steric bulk of 1, methyl groups were added to the ethylene carbon atoms between the oxygen atoms resulting in ligand 2. This methyl substitution pattern was chosen because metal–environment interactions occur between the unmodified ethylene groups.[8] Furthermore, to examine the influence of Lewis basicity on oxidative stability, phenyl rings were introduced to decrease the electron-donating ability of the adjacent oxygen atoms of ligands 3–5 by a resonance withdrawing effect.[12] The extent of electron withdrawal was modulated by varying the electron density of the phenyl ring through the addition of a fluorine atom (4) or by increasing the number of rings (5). Phenyl-ring-containing cryptands 3–5 also have an influence on cavity size because each phenyl ring decreases the cavity size of the cryptand. We expected the seemingly minor influence of the phenyl rings on cavity size to have a noticeable effect on the oxidative stability of EuII because of selectivity studies with Group 2 cations using cryptands 1, 3, and 5.[13] Finally, relatively soft sulfur-atom donors were introduced in cryptand 6 in place of oxygen-atom donors to explore the HSAB preferences for the softer EuII ion relative to the harder EuIII ion. To synthesize the diverse set of cryptands 1–6, a three-step procedure was devised that involved common intermediates 7, 9, and 11 (Scheme 2).[14] Briefly, the synthesis involved the conversion of the appropriate ethylenediols or catechols into the corresponding ditosylates (7, 9, and 11) and subsequent ring closure with 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane, 2,2′-(ethylenedioxy)bis(ethylamine), or 1,4,10,13-tetrathia-7,16-diazacyclooctadecane. Metal complexation was achieved in situ by mixing Eu(NO3)3·5H2O and the desired cryptand (1–6) in aqueous solution under an Ar atmosphere. The resulting solution was placed in a standard three-electrode cell (glassy-carbon working electrode, platinum-wire auxiliary electrode, and Ag/AgCl (1.0M KCl) reference electrode). The potential at the carbon electrode was held at −0.8 V (vs. Ag/AgCl) while stirring to produce EuII in situ for metalation.[7] After metalation, cyclic voltammograms were obtained for each complex in solution with ferrocene as an internal standard:[9,15] a new anodic peak was observed for each complex at a more positive potential than the peak corresponding to oxidation of the aqueous EuII (Table 1). These data indicate that each cryptand imparted additional stability to EuII as hypothesized. Scheme 2 Synthetic route to cryptands 2 and 4–6 using common intermediates 7, 9, and 11. Table 1 Anodic peak potentials (Epa) with respect to ferrocene/ferrocenium (Fc/Fc+). The cyclic voltammetric data of europium-containing solutions of 1 and 2 demonstrate that the increased steric bulk in cryptand 2 leads to increased oxidative stability over unmodified cryptand 1. Furthermore, a more targeted examination of the influence of Lewis basicity on oxidative stability was achieved by examining the impact of ligands 3–5. We observed that one phenyl ring on cryptand 3 was sufficient to stabilize EuII oxidatively by 128 mV with respect to the unmodified cryptand 1-Eu. This stabilization is likely due to a combination of the decrease in Lewis basicity of the adjacent oxygen atoms (better for electron-rich metals) and the reduction in cavity size caused by the phenyl ring (better match for the size of the EuII ion). However, the addition of a second phenyl ring (5) caused no difference in the anodic peak potential compared to the monophenyl cryptand 3 (p = 0.76). This effect is likely due to reduction of the cavity size counteracting the decreased basicity of the ligand, thus suggesting that a minimum cavity size for EuII stabilization was achieved with cryptand 3. Further decrease in Lewis basicity through the addition of a fluorine substituent to the phenyl ring (4) led to 129 mV greater stability than what was observed with unsubstituted monophenyl cryptand 3. In addition, the oxidative stability of 4-Eu is not different from that of FeII in hemoglobin (p = 0.45). Finally, replacement of the harder oxygen atoms with softer sulfur atoms (6) produced the most dramatic stabilization effect of our cryptand series. This modification increased the oxidative stability of EuII by 173 mV compared to the structurally similar cryptand 3. The cavity size of cryptand 6 increases slightly because of the increased bond length of C–S compared to C–O, thus suggesting that a decrease in stability should be observed based on the difference between cryptands 1 and 3. However, the effect of cavity size is small relative to the influence of HSAB matching between EuII and sulfur. Cryptand 6 with EuII produces an oxidative potential that is 666 mV more positive than the aqueous EuII and 35 mV more positive than FeII in hemoglobin. To the best of our knowledge, this oxidative stability of EuII is the highest reported in aqueous solution and indicates the potential for the use of EuII in vivo. We observed dramatic oxidative stabilization of EuII using modified cryptands. These trends in stability suggest that further stabilization of aqueous EuII and other lanthanide ions is possible. We are currently pursuing these avenues of research in addition to measuring the thermodynamic stability of the EuII complexes reported here. Finally, our most stable complex, with an oxidation potential indicative of biological oxidative stability, opens the door for the use of the magnetic and spectroscopic properties of EuII in vivo.

Existe consenso respecto a las desventajas generadas por una expansion urbana incontrolada. Esta demostrado en numerosos sectores que la falta de planeacion del crecimiento produce efectos desastrosos en la ciudad: falta y/o desorganizacion del transporte colectivo en distintas areas de las ciudades, en general las de urbanizacion reciente; servicios publicos insuficientes e ineficientes (ausencia de infraestructura de agua, recoleccion de basura desigual en el territorio, etc.); equipamientos urbanos ausentes; invasion de terrenos y areas naturales; perdida de identidad e integracion social; paisajes urbanos poco alentadores; etc. En la presente ponencia, y frente al consenso existente a escala mundial y a los multiples ejemplos de fracaso urbano debido a una expansion horizontal incontrolada, se acepta esta premisa que no se integrara al debate: no a la expansion no planeada.