Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2'-bipyridine and ethylenediamine and their interaction with human serum albumin

Complex formation equilibri um processes of the (N,N) donor containing 2,2' - bipyridine (bpy) and ethylenediamine (en) with (η 5 - pentamethylcyclopentadienyl) rhodium(III) were investigated in aqueous solution via pH - potentiome try, 1 H NMR spectroscopy, and UV – Vis spectrophotometry in the absence and presence of chloride ions . The structure of [RhCp*(en)Cl]ClO 4 (Cp* , pentamethylcyclopentadienyl ) was also studied b y single - crystal X - ray diffraction. p K a values of 8.56 and 9.58 we re determined for [RhCp*(bpy)(H 2 O)] 2+ and [RhCp*(en)(H 2 O)] 2+ , respectively resulting in the formation of negligible amount of mixed hydroxido complexes at pH 7.4 . Stability and the H 2 O/Cl ‒ co - ligand exchange constants of bpy and en complexes considerably exceed those of the bidentate O - donor deferiprone. The strong affinity of the bpy and en complexes to chloride ions most probably contribute s to their low antiproliferative effect. Interac tion s between human serum albumin (HSA) and [ RhCp* (H 2 O) 3 ] 2+ , its complexes formed with deferiprone, bpy and en were also monitored by 1 H NMR spectroscopy, ultrafiltration/ UV - Vis and spectrofluorometry. Numerous binding sites ( ≥ 8 ) are available for [RhCp* (H 2 O) 3 ] 2+ ; and the interaction takes place most probably via covalent bonds through the imidazole nitrogen of His . According to the various fluorescen ce studies [RhCp* (H 2 O) 3 ] 2+ binds on sites I and II , and coordination of surface side chain donor atoms of th e protein is also feasible. The binding of the bpy and en complex is weaker and slower compared to that of [RhCp* (H 2 O) 3 ] 2+ , and formation of ternary HSA - RhCp* - ligand adducts was proved. I n the case of the deferiprone complex , the RhCp* fragment is cleaved off when HSA is loaded with low equivalents of the comp ound

Half-Sandwich Rhodium Complexes with Releasable N-Donor Monodentate Ligands: Solution Chemical Properties and the Possibility for Acidosis Activation

Cancer chemotherapeutics usually have serious side effects. Targeting the special properties of cancer and activation of the anticancer drug in the tumor microenvironment in situ may decrease the intensity of the side effects and improve the efficacy of therapy. In this study, half-sandwich Rh complexes are introduced, which may be activated at the acidic, extracellular pH of the tumor tissue. The synthesis and aqueous stability of mixed-ligand complexes with a general formula of [Rh(η5-Cp*)(N,N/O)(N)]2+/+ are reported, where (N,N/O) indicates bidentate 8-quinolate, ethylenediamine and 1,10-phenanthroline and (N) represents the releasable monodentate ligand with a nitrogen donor atom. UV-visible spectrophotometry, 1H NMR, and pH-potentiometry were used to determine the protonation constants of the monodentate ligands, the proton dissociation constants of the coordinated water molecules in the aqua complexes, and the formation constants of the mixed-ligand complexes. The obtained data were compared to those of the analogous Ru(η6-p-cymene) complexes. The developed mixed-ligand complexes were tested in drug-sensitive and resistant colon cancer cell lines (Colo205 and Colo320, respectively) and in four bacterial strains (Gram-positive and Gram-negative, drug-sensitive, and resistant) at different pH values (5–8). The mixed-ligand complexes with 1-methylimidazole displayed sufficient stability at pH 7.4, and their activation was found in cancer cells with decreasing pH; moreover, the mixed-ligand complexes demonstrated antimicrobial activity in Gram-positive and Gram-negative bacteria, including the resistant MRSA strain. This study proved the viability of incorporating releasable monodentate ligands into mixed-ligand half-sandwich complexes, which is supported by the biological assays

Community Pharmacy Recruitment for Practice-Based Research: Challenges and Lessons Learned

To support the successful integration of community pharmacies into value-based care models, research on the feasibility and effectiveness of novel pharmacist-provided patient care services is needed. The UNC Eshelman School of Pharmacy, supported by the National Association of Chain Drug Stores (NACDS) Foundation, designed the Community-based Valued-driven Care Initiative (CVCI) to (1) identify effective value-based patient care interventions that could be provided by community pharmacists, (2) implement and evaluate the feasibility of the selected patient care interventions, and (3) develop resources and create collaborative sustainability opportunities. The purpose of this manuscript is to describe recruitment strategies for CVCI and share lessons learned. The project team identified pharmacies for recruitment through a mixed data analysis followed by a “fit” evaluation. A total of 42 pharmacy organizations were identified for recruitment, 24 were successfully contacted, and 9 signed on to the project. During recruitment, pharmacies cited concerns regarding the financial sustainability of implementing and delivering the patient care services, challenges with staffing and infrastructure, and pharmacists’ comfort level. To foster participation, it was vital to have leadership buy-in, clear benefits from implementation, and assured sustainability beyond the research period

Half-Sandwich Rhodium Complexes with Releasable N-Donor Monodentate Ligands: Solution Chemical Properties and the Possibility for Acidosis Activation

Cancer chemotherapeutics usually have serious side effects. Targeting the special properties of cancer and activation of the anticancer drug in the tumor microenvironment in situ may decrease the intensity of the side effects and improve the efficacy of therapy. In this study, half-sandwich Rh complexes are introduced, which may be activated at the acidic, extracellular pH of the tumor tissue. The synthesis and aqueous stability of mixed-ligand complexes with a general formula of [Rh(η5-Cp*)(N,N/O)(N)]2+/+ are reported, where (N,N/O) indicates bidentate 8-quinolate, ethylenediamine and 1,10-phenanthroline and (N) represents the releasable monodentate ligand with a nitrogen donor atom. UV-visible spectrophotometry, 1H NMR, and pH-potentiometry were used to determine the protonation constants of the monodentate ligands, the proton dissociation constants of the coordinated water molecules in the aqua complexes, and the formation constants of the mixed-ligand complexes. The obtained data were compared to those of the analogous Ru(η6-p-cymene) complexes. The developed mixed-ligand complexes were tested in drug-sensitive and resistant colon cancer cell lines (Colo205 and Colo320, respectively) and in four bacterial strains (Gram-positive and Gram-negative, drug-sensitive, and resistant) at different pH values (5–8). The mixed-ligand complexes with 1-methylimidazole displayed sufficient stability at pH 7.4, and their activation was found in cancer cells with decreasing pH; moreover, the mixed-ligand complexes demonstrated antimicrobial activity in Gram-positive and Gram-negative bacteria, including the resistant MRSA strain. This study proved the viability of incorporating releasable monodentate ligands into mixed-ligand half-sandwich complexes, which is supported by the biological assays

Preserving Mobility in Older Adults with Physical Frailty and Sarcopenia : Opportunities, Challenges, and Recommendations for Physical Activity Interventions

One of the most widely conserved hallmarks of aging is a decline in functional capabilities. Mobility loss is particularly burdensome due to its association with negative health outcomes, loss of independence and disability, and the heavy impact on quality of life. Recently, a new condition, physical frailty and sarcopenia, has been proposed to define a critical stage in the disabling cascade. Physical frailty and sarcopenia are characterized by weakness, slowness, and reduced muscle mass, yet with preserved ability to move independently. One of the strategies that have shown some benefits in combatting mobility loss and its consequences for older adults is physical activity. Here, we describe the opportunities and challenges for the development of physical activity interventions in people with physical frailty and sarcopenia. The aim of this article is to review age-related physio(patho)logical changes that impact mobility in old age and to provide recommendations and procedures in accordance with the available literature.Peer reviewe