Solid-phase Approach Research Articles

Total Synthesis of Marformycins A and D.

We report the synthesis of the antimicrobial cyclodepsipeptides marformycin A (1) and marformycin D (2) using a solid-phase approach. A scalable solution-phase synthesis of the γ-hydroxypiperazic acid subunit in 2, starting from cis-hydroxyproline, is also described. Structural analysis of 1 and its Leu-epi congener demonstrates conformational differences that may underlie their divergent antimicrobial activities. The described approach enables further development of conformation-activity relationships within this class of depsipeptide natural products.

Facile Synthesis of Fluorescent Carbon Quantum Dots with High Product Yield Using a Solid-Phase Strategy

The liquid-phase method is the most commonly utilized strategy for synthesizing fluorescent carbon quantum dots (CQDs). However, the liquid-phase synthesis of CQDs faces challenges such as low yield, complex purification, and the use of toxic solvents, which limit large-scale production and practical applications. In this study, fluorescent CQDs with a high product yield of 78% were synthesized using glucose as a carbon source through a green and facile one-step solid-phase approach, without solvents or post-treatment. A systematic study of the structure and fluorescence properties of the synthesized CQDs was conducted using various characterization techniques. The results indicated that the mean size of obtained CQDs was 4.1 nm, and that their surface had abundant oxygen-containing functional groups, resulting in favorable water solubility. The synthesized CQDs exhibited excitation-dependent fluorescence, with optimal excitation and emission wavelengths at 358 and 455 nm, respectively. Additionally, the CQDs solution showed bright blue fluorescence under 365 nm UV light, with a quantum yield of 6.21% and a fluorescence lifetime of 3.02 ns. This study offers valuable insights into the green and efficient synthesis of fluorescent CQDs powder.

Solid state synthesis of Ce-doped zircon from the mechanically activated CeO2–ZrO2–SiO2 mixture

Zircon is a promising candidate for use as a matrix in the immobilization of radioactive waste. However, high temperatures (1400–1600 °C) and calcination durations are generally required to produce it. In this letter, we report the synthesis of cerium-containing solid solution based on zircon Zr1-xCexSiO4 by means of a straightforward and environmentally sustainable milling-assisted solid-phase approach conducted at a reduced temperature. Our study demonstrated that the utilization of mechanical activation of the oxide mixture in a mill not only diminished the temperature (to 1200 °C) and the duration of calcination but also increased the Ce content in zircon up to 6.4 at.%. Additionally, we propose a novel method for determining the phase composition of calcined samples using Vegard's law and mass balance.

Recent solid-phase microextraction-based analytical approaches for the profiling of biliary bile acids in pre-transplant assessments of liver grafts subjected to normothermic ex vivo liver perfusion

BackgroundLiver transplantation is the definitive treatment for end-stage liver failure, but the scarcity of donor organs remains a significant challenge. Leveraging organs from extended criteria donors (ECD) offers a potential avenue to address worldwide shortages, though these organs are more susceptible to post-reperfusion injury. This study explores the use of normothermic ex vivo liver perfusion (NEVLP) as a method for organ preservation – an approach that sustains liver metabolism and facilitates pre-transplant assessments of organ viability via bile analysis. The focal point of this study revolves on the development of analytical methods for determining the bile acid profile throughout the peritransplantation period as a potential indicator of liver function and viability. ResultsThe study optimized and validated a high-throughput analytical method to quantify selected bile acids in bile samples using a thin-film microextraction-liquid chromatography-mass spectrometry (TFME-LC-MS) platform. Furthermore, it introduced a solid-phase microextraction-microfluidic open interface-mass spectrometry (SPME-MOI-MS) method for rapid direct analysis of bile acid isobar groups. In the animal study, discernible variations in the concentrations of specific bile acids were observed between donors after circulatory death (DCD) and heart-beating donors (HBD), particularly following normothermic perfusion and reperfusion. Noteworthy fluctuations in individual bile acid concentrations were observed throughout the entire organ transplantation process, with taurocholic acid (TCA), glycocholic acid (GCA), and glycochenodeoxycholic acid (GCDCA) emerging as promising indicators of organ quality. The efficacy of the SPME-MOI-MS platform in corroborating these trends highlights its potential for real-time bile acid analysis during liver transplantation procedures. SignificanceOur findings underscore the efficacy of NEVLP in tandem with advanced bile acid analysis methods as a reliable strategy for pre-transplant assessments of organ viability, potentially increasing the use of ECD organs and reducing organ shortages. The ability to monitor bile acid profiles in real-time provides crucial insights into liver function and ischemic injury, making significant strides in improving transplant outcomes and patient survival rates.

Peptide direct growth on poly(acrylic acid)/poly(vinyl alcohol) electrospun fibers coated with branched poly(ethylenimine): A solid-phase approach for scaffolds biofunctionalization

Due to their resemblance to the fibrillar structure of the extracellular matrix, electrospun nanofibrous meshes are currently used as porous and mechanically stable scaffolds for cell culture. In this study, we propose an innovative methodology for growing peptide sequences directly onto the surface of electrospun nanofibers. To achieve this, electrospun fibers were produced from a poly(acrylic acid)/poly(vinyl alcohol) blend that was thermally crosslinked and subjected to a covalent coating of branched poly(ethylenimine). The exposed amino functionalities on the fiber surface were then used for the direct solid-phase synthesis of the RGD peptide sequence. In contrast to established strategies, mainly involving the grafting of pre-synthesized peptides onto the polymer chains before electrospinning or onto the nanofibers surface, this method allows for the concurrent synthesis and anchoring of peptides to the substrate, with potential applications in combinatorial chemistry. The incorporation of this integrin-binding motive significantly enhanced the nanofibers' ability to capture human cervical carcinoma (HeLa) cells, selected as a proof of concept to assess the functionalities of the developed material.

Enhanced simulated sunlight photocatalytic performance in K2Ti6O13/g-C3N4 heterojunction

In this study, K2Ti6O[Formula: see text] (KTO) nanowires were doped with carbon (CKTO) via a novel solid-phase approach at 800∘C for the first time using ethanol, KF, and TiO2. In addition to the lower sintering temperature, a shorter insulation period was achieved compared to the conventional solid-phase method. Furthermore, by combining and calcining CKTO and g-C3N4, a CKTO/g-C3N4 heterojunction composite was produced. The rate at which CKTO/g-C3N4 photocatalytically degraded methylene blue was higher than those of pure CKTO and g-C3N4. Our study indicates that adding g-C3N4 enhances photocatalytic performance by reducing the recombination rate of photogenerated electron–hole pairs and narrowing the bandgap of the CKTO/g-C3N4 heterostructure. This paper presents a novel method for creating KTO composites in an eco-friendly and productive manner for the photocatalytic degradation of organic colors.

Multi-color and multi-mode luminescence tuning in persistent phosphors by trap engineering

Conventional persistent luminescent phosphors face a significant challenge in developing a single material for multi-color anti-counterfeiting. In this study, a wide range of Cr3+ activated gallium germanate-based persistent phosphors are successfully synthesized using high-temperature solid phase approach. By incorporating Cr3+ and Er3+ as dual emitting centers, and utilizing Yb3+ as a sensitizer and electron traps, the resulting phosphors exhibit an exceptional combination of photoluminescence, up-conversion luminescence, persistent luminescence, photo/thermo-stimulated luminescence, followed by photo-stimulated persistent luminescence in a single material system. Beyond its multi-mode emissions, the luminescence color output can be conveniently controlled by adjusting annealing time, Yb3+ ion doping concentration, excitation wavelength, or excitation power. A systematic study of trap distribution related to PersL has been conducted by regulating annealing temperature, time, doping concentration and type. The responding multi-mode luminescent mechanisms are also proposed. Particularly, these phosphors demonstrated outstanding performance as security labels in advanced anti-counterfeiting applications. This research holds the potential to inspire the design and development of more intricate luminescence anti-counterfeiting materials and technologies.

Thermally stable Tb3+/Sm3+-doped Lu2O2S phosphors with tunable multicolor luminescence under light and X-ray excitation

Lu2O2S has high density, high melting temperature, and favorable thermal stability, making it an excellent matrix material for rare earth luminescence and X-ray sensitization screens. However, achieving high quality fluorescent powders with high crystal quality on a large scale is still challenging. By employing an optimized solid phase approach, Lu2O2S:Tb3+/Sm3+phosphors with a hexagonal shape and uniform particle size and showing high crystallization have been successfully synthesized. Spectral analysis reveals energy interaction between Sm3+ and Tb3+ in the Lu2O2S system (multistage interaction), indicated by spectral overlap, relative changes in luminescence intensity, and lifetime decay. By changing the excitation wavelength and dopant concentration, multicolor phosphors such as yellow-–green, orange–red, and orange–yellow could be created. Temperature-dependent emission spectroscopy shows that the system shows good luminescence performance even at high temperatures. X-ray excitation spectroscopy further confirm that the phosphors emit different colors (yellow, green and red) depending on the doping concentrations of Tb3+ and Sm3+ ion, indicating that the system has wide application potential in color displays and other relevant fields.

Nondestructive assessment of ZnO surge arrester operating condition based on time-domain dielectric characteristics

Given the expansion of the economy and the rise in electricity demand, it is imperative to ensure the safe operation of the power system. Zinc oxide (ZnO) surge arresters play a crucial role in preventing overvoltage that can potentially harm the grid. The study presents an innovative non-destructive assessment approach for evaluating the working condition of ZnO surge arresters based on time-domain dielectric characteristics, aiming to guarantee their safe functioning within the power grid. The proposed technique provides a platform for conducting aging experiments updates the procedure for preparing piezoresistors in ZnO surge arresters and examines their performance. Furthermore, a test bed was utilized to investigate polarization/depolarization currents. The findings revealed that the pressure-sensitive voltage exhibited a minimum value of 693.09 U1mA ·cm2 using the traditional solid-phase approach while employing the chemical precipitation method with a 2:1 alcohol-to-water volume ratio resulted in a maximum value of 1028.41 U1mA ·cm2. Under the traditional solid-phase method, the voltage gradient varied from 411.04 V·mm−1 to 585.12 V·mm−1 when using the chemical precipitation method with an alcohol-to-water volume ratio of 2:1 V ·mm−1. The condition of ZnO surge arresters can be evaluated non-destructively by the polarization/depolarisation charge differential, which increases with the average service life. In conclusion, this study provides methodological criteria for assessing ZnO surge arrester conditions to ensure safe operation of power grids.

Highly selective CuO-ZnO@Cu-MOR catalysts prepared by ultrafast solid processing for carbon dioxide hydrogenation to methanol

The conversion of CO2 into methanol has emerged as a promising strategy for addressing climate change and optimizing the utilization of carbon resources. Conventional synthesis methods for Cu-based catalysts, such as co-precipitation, necessitate the consumption of substantial amounts of solvent and meticulous control over preparation conditions, while also being susceptible to deactivation by water during hydrogenation. Therefore, it is crucial to develop a catalyst that can be readily synthesized and exhibits outstanding performance and durability. In this study, we present an ultrafast (only 20 min), solid-phase grinding approach to fabricate CuO-ZnO@Cu-MOR catalysts for CO2 hydrogenation to methanol. The resulting catalysts were comprehensively characterized using XRD, XPS, H2-TPR, NH3-TPD, SEM, HRTEM, and In-situ-FTIR techniques. Notably, the CuO-ZnO@Cu-MOR catalysts with a distinctive capsule-like structure displayed a high catalytic performance for CO2 hydrogenation. The byproducts of methane and water produced by the CO2 hydrogenation process were able to be further converted to methanol through Cu-MOR, leading to a significant enhancement of the methanol selectivity (95.6 %) and CO2 conversion (22.8 %). Moreover, a long-term test lasting 300 h demonstrated constant catalytic performances and superior durability.

Crystal structure of strontium aluminates phosphors containing bismuth oxides

The composite phosphors SrAl2O4/Sr3Al2O6:Bi2O3/Bi2O4 synthesized by a solid-phase approach have been studied by means of X-ray diffraction, Raman spectroscopy, and optical spectroscopy methods. A redistribution of Bi3+ ions between two phases was observed by changes in crystal parameters, bond length, and vibrational frequencies on Raman spectra. A relationship between the structure of the host matrix and the optical characteristics of phosphors has been established.

Space-confined solid-phase growth of two-domain 1T′-ReSe2 for tunable optoelectronics

Two-dimensional layered ReX2 (X = Se, S) has attracted researcher's great interest due to its unusual in-plane anisotropic optical and electrical properties and great potential in polarization-sensitive optoelectronic devices, while the clean, energy-saving, and ecological synthesis of highly crystalline ReSe2 with controlled domains remains challenging. Here, we develop a space-confined solid-phase approach for growing high-quality two-domain 1T′-ReSe2 with tunable optoelectronic properties by using pure Re powder as a Re precursor. The results show that ReSe2 can be grown at a temperature as low as 550 °C in a small-tube-assisted space-confined reactor, with its size and shape well-tailored via temperature control. A solid-phase two-domain ReSe2 growth mechanism is proposed, as evidenced by combining in situ optical monitoring, ex situ electron microscope, elemental mapping, and polarized optical imaging. Moreover, two-domain ReSe2 transistors are fabricated, which exhibit a switchable transport behavior between n-type and ambipolar character via grain boundary orientation control. This modulation phenomenon is attributed to the different doping levels between grain boundary and single domain. Furthermore, our two-domain ReSe2 photodetectors exhibit a highly gate-tunable current on–off ratio (with a maximum value of ∼8.2 × 103), a polarization-sensitive photo-response, and a high-speed response time (∼300 μs), exceeding most of the previously reported ReX2 photodetectors. Our work, thus, provides a low-consumption, energy-saving growth strategy toward high-quality, domain-controlled ReX2 for highly tunable and high-performance optoelectronics.

A performance comparison of photo-fenton decolorization of methylene blue by using bentonite/iron composites prepared by liquid phase and solid phase ion exchange method

Nowadays, there is a wide range of pollutants present, which requires the treatment of wastewater. The photo-Fenton method has been recognized as valuable in this area. In this study, iron/bentonite composites were created using both liquid phase and solid phase iron exchange techniques, and they were utilized as a photocatalyst for the degradation of methylene blue through photo-Fenton process. Various factors affecting the photocatalytic decolorization were investigated, including the initial concentration of the dye, weight of the catalyst, pH of the solution, and concentration of hydrogen peroxide. The decolorization efficiency of the iron/bentonite composites prepared using the solid phase and liquid phase ion exchange approaches was found to be 99% and 95%, respectively. Based on the data, it can be concluded that the performance of both catalysts was almost equally influenced by the initial dye concentration, catalyst weight, solution pH, and hydrogen peroxide concentration. Moreover, the solid phase ion exchange method demonstrated greater reusability compared to the liquid phase ion exchange method. Consequently, it can be stated that the solid phase ion exchange approach is a suitable and straightforward alternative to the conventional liquid phase ion exchange method for producing a photo-Fenton catalyst.

Cu2CoSnS4 electrocatalyst embedded paper working electrodes for efficient, stable, pH universal, and large-current-density hydrogen evolution reaction

In this study, practical application for the industrial-scale hydrogen evolution reaction (HER) process is established using sustainable Cu2CoSnS4 embedded in paper-working electrodes. The Cu2CoSnS4 is produced using a solvent-free solid-phase approach. The effect of a wide pH range of electrolytes on working electrodes for hydrogen evolution reactions is also investigated. The Cu 2CoSnS4 embedded paper-working electrodes exhibit goodelectrocatalytic activity for hydrogen evolution reaction with low overpotential values of 233, 310, and 261 mV vs RHE at 10 mA/cm 2 in 0.5 M H2SO4,1 M KOH, and 1 M PBS, respectively. These designed electrodes exhibit high double-layer capacitance and electrochemical surface area for a wide pH range. In acidic, alkaline and neutral environments, the catalyst-embedded paper electrodes explicit high turnover frequencies of 2.15 s−1, 2.75 s−1, and 2.11 s−1, respectively. The temperature-dependent hydrogen evolution reaction is studied to calculate the activation energy of the cathodic electrode. Utilising chrono-amperometry for about 118 h in an acidic media, which shows that electrodes have a high degree of stability. In comparison to other previously reported work on catalyst-embedded electrodes, the Cu2CoSnS4 embedded paper-working electrodes offer excellentpotential for HER activity across a wide pH range and are suitable for industrial application.

Hydrophobic Bombyx mori Silk Fibroin: Routes to Functionalization with Alkyl Chains

AbstractBombyx mori silk fibroin (SF) is a very versatile biopolymer due to its biocompatibility and exceptional mechanical properties which make possible its use as a functional material in several applications. SF can be modified with a large variety of chemical approaches which endow the material with tailored chemical–physical properties. Here, a systematic investigation of different routes is reported to graft long alkyl chains on SF based on both liquid‐ and solid‐phase, aiming to modulate its hydrophobic behavior. The liquid phase method involves direct activation of SF tyrosine residues via diazo coupling and cycloaddition reactions, generating hydrophobic materials insoluble in any common solvent. The solid phase approach consists of the chemical modification of drop‐casted SF films by esterification of hydroxyl groups of serine, threonine, and tyrosine SF residues with acyl chlorides of fatty acids. For the solid‐state functionalization, a new class of hydrophobic pendant groups is synthesized, based on triple esters of gallic acid anhydrides, that are reacted with the biopolymer to further enhance its resulting hydrophobic features.

Synthesis of cell penetrating peptide sterol coupler and its liposome study on S-mRNA

In order to overcome the current LNP-mRNA delivery system's weakness of poor stability and rapid degradation by nuclease, a novel chol-CGYKK molecule and then the new phospholipid liposome were designed and prepared. A solid phase approach synthesized CGYKK and connected it to cholesterol via a disulfide linker to form the desired chol-CGYKK. Four formulated samples with different proportions of excipients were prepared by freeze-drying cationic liposomes and packaged S-mRNA. The stability test shows that after six months at 4 °C, the encapsulation rate of this novel phospholipid liposome was still approximately 90%, which would significantly improve the storage and transportation requirement. Transmission electron microscopy, atomic force microscopy, and scanning electron microscopy indicated that the liposomes were spherical and uniformly dispersed. On comparing the levels of mRNA protein expression of the four formulated samples, the S protein vaccine expression of formulated sample 1 was the highest. Uptake by vector cells for formulated sample 1 showed that compared to Lipo2000, and the transfection efficiency was 66.7%. Furthermore, the safety evaluation of the CGYKK and mRNA vaccine liposomes revealed no toxic effects. The in vivo study demonstrated that this novel mRNA vaccine had an immune response. However, it was still not as good as the LNP group right now, but its excellent physicochemical properties, stability, in vitro biological activity, and in vivo efficacy against SARS-CoV-2 provided new strategies for developing the next generation of mRNA delivery system.

Solid-Phase Synthesis of PROTACs and SNIPERs on Backbone Amide Linked (BAL) Resin.

Developing straightforward but flexible approaches to PROTAC synthesis that can incorporate the structural elements of emerging designs can improve the quality and efficiency of PROTAC development. Solid-phase approaches could offer many advantages over conventional PROTAC synthesis if diverse chemistries and topographies can be incorporated. We have exploited the backbone-amide-linked (BAL) resin to employ an array of solid-phase organic reactions, providing access to VHL- and IAP-targeting degraders using the BRD4-targeting JQ1 conjugates as examples.

Development of Molecularly Imprinted Polymer Nanoparticles with High Affinity and Its Application to Electrochemical Biosensors

Molecularly imprinted polymers (MIPs) have the potentials to be low-cost and stable alternatives to natural receptors such as enzymes and antibodies for biosensors. In our group, we have been developing enzyme-/antibody-free electrochemical biosensors with the MIP-coated electrodes [1,2]. However, the conventional polymerization methods for MIPs have the limitations such as their heterogeneities that reduce high binding affinity sites and the presence of residual templated molecules, which are detrimental to biomolecular recognition. To address these issues, we have synthesized molecularly imprinted polymer nanoparticles (nano-MIPs) with virtually free of heterogeneous templates and higher affinity for target biomolecules by using a solid-phase approach synthesis method [3]. In this study, we have focused on the biomarkers such as human serum albumin (HSA) and glycated albumin (GA) for diabetes and then synthesized the redox-labeled HSA-templated nano-MIPs (HNMs) and GA-templated nano-MIPs (GNMs) for the electrochemical biosensor (Figure 1). The fundamental characteristics of HNMs and GNMs such as chemical composition, particle size, and binding affinity have been evaluated by using proton nuclear magnetic resonance (1H NMR), dynamic light scattering (DLS), atomic force microscopy (AFM), cyclic voltammetry (CV), isothermal titration calorimetry (ITC), and surface plasmon resonance (SPR).References Kajisa, T.; Sakata, T. ACS Appl. Mater. Interfaces 2018,10, 34983–34990.Sakata, T.; Nishitani, S.; Kajisa, T. RSC Advances 2020, 10, 16999–17013.Canfarotta, F. et al. Nat. Protoc. 2016, 3, 443-455. Figure 1

Methods for the purification and detection of single nucleotide KRAS mutations on extrachromosomal circular DNA in human plasma.

Despite recent advances, many cancers are still detected too late for curative treatment. There is, therefore, a need for the development of new diagnostic methods and biomarkers. One approach may arise from the detection of extrachromosomal circular DNA (eccDNA), which is part of cell-free DNA in human plasma. First, we assessed and compared two methods for the purification of eccDNA from plasma. Second, we tested for an easy diagnostic application of eccDNA liquid biopsy-based assays. For the comparison we tested a solid-phase silica purification method and a phenol/chloroform method with salt precipitation. For the diagnostic application of eccDNA we developed and tested a qPCR primer-based SNP detection system, for the detection of two well-established cancer-causing KRAS mutations (G12V and G12R) on circular DNA. This investigation was supported by purifying, sequencing, and analysing clinical plasma samples for eccDNAs containing KRAS mutant alleles in 0.5 mL plasma from 16 pancreatic ductal adenocarcinoma patients and 19 healthy controls. In our method comparison we observed, that following exonuclease treatment a lower eccDNA yield was found for the phenol/chloroform method (15.7%-26.7%) compared with the solid-phase purification approach (47.8%-65.9%). For the diagnostic application of eccDNA tests, the sensitivity of the tested qPCR assay only reached ~10-3 in a background of 105 wild type (wt) KRAS circular entities, which was not improved by general amplification or primer-based inhibition of wt KRAS amplification. Furthermore, we did not detect eccDNA containing KRAS in any of the clinical samples. A potential explanation for our inability to detect any KRAS mutations in the clinical samples may be related to the general low abundance of eccDNA in plasma. Taken together our results provide a benchmark for eccDNA purification methods while raising the question of what is required for the optimal fast and sensitive detection of SNP mutations on eccDNA with greater sensitivity than primer-based qPCR detection.

De Novo Approaches to the Solid-Phase Separation of Titanium(IV) and Scandium(III): Translating Speciation Data to Selective On-Bead Chelation toward Applications in Nuclear Medicine.

The solution chemistry of the hydrolytic, early-transition-metal ions Ti4+ and Sc3+ represents a coordination chemistry challenge with important real-world implications, specifically in the context of 44Ti/44Sc and 45Ti/NatSc radiochemical separations. Unclear speciation of the solid and solution phases and tertiary mixtures of mineral acid, organic chelators, and solid supports are common confounds, necessitating tedious screening of multiple variables. Herein we describe how thermodynamic speciation data in solution informs the design of new solid-phase chelation approaches enabling separations of Ti4+ and Sc3+. The ligands catechol (benzene-1,2-diol) and deferiprone [3-hydroxy-1,2-dimethyl-4(1H)-pyridone] bind Ti4+ at significantly more acidic conditions (2-4 pH units) than Sc3+. Four chelating resins were synthesized using either catechol or deferiprone with two different solid supports. Of these, deferiprone appended to carboxylic acid polymer-functionalized silica (CA-Def) resin exhibited excellent binding affinity for Ti4+ across a wide range of HCl concentrations (1.0-0.001 M), whereas Sc3+ was only retained in dilute acidic conditions (0.01-0.001 M HCl). CA-Def resin produced separation factors of >100 (Ti/Sc) in 0.1-0.4 M HCl, and the corresponding Kd values (>1000) show strong retention of Ti4+. A model 44Ti/44Sc generator was produced, showing 65 ± 3% yield of 44Sc in 200 μL of 0.2 M HCl with a significant 44Ti breakthrough of 0.1%, precluding use in its current form. Attempts, however, removed natSc in loading fractions and a dilute (0.4 M HCl) wash and recovered 80% of the loaded 45Ti activity in 400 μL of 6 M HCl. The previously validated 45Ti chelator TREN-CAM was used for comparative proof-of-concept reactions with the CA-Def eluent (in HCl) and literature-reported hydroxamate-based resin eluents (in citric acid). CA-Def shows improved radiolabeling efficiency with an apparent molar activity (AMA) of 0.177 mCi nmol-1, exceeding the established methods (0.026 mCi nmol-1) and improving the separation and recovery of 45Ti for positron emission tomography imaging applications.