Tuning the Properties of Rigidified Acyclic DEDPA Derivatives for Application in PET Using Copper-64.

We present a detailed investigation of the coordination chemistry toward [Cu/Cu]copper of a series of HDEDPA derivatives (HDEDPA = 6,6'-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid) containing cyclohexyl (HCHXDEDPA), cyclopentyl (HCpDEDPA) or cyclobutyl (HCBuDEDPA) spacers. Furthermore, we also developed a strategy that allowed the synthesis of a HCBuDEDPA analogue containing an additional NHBoc group at the cyclobutyl ring, which can be used for conjugation to targeting units. The X-ray structures of the Cu(II) complexes evidence distorted octahedral coordination around the metal ion in all cases.

Examining the Cycle of Physical Frailty in Falls Clinic Attendees Through Structural Equation Modeling.

In 1998, Fried and Walston introduced the Cycle of Frailty (CF) as a foundational concept for defining the physical frailty phenotype (FP). While the FP has been extensively validated, the CF hypothesis lacks equivalent support. This study aimed to internally validate the CF using structural equation modeling (SEM) in a clinical dataset of adults aged 50 or older attending an outpatient falls clinic.

Correction: What gaps remain in the HIV cascade of care? Results of a population-based survey in Nsanje District, Malawi.

[This corrects the article DOI: 10.1371/journal.pone.

Turkish version of the SHARE-Frailty Instrument for primary care: reliability and validity in the nursing home setting.

In Turkey, physical frailty instruments have not been studied in the nursing home setting. We determined the reliability and validity of a Turkish version of the SHARE-Frailty Instrument for primary care (SHARE-FI) in Turkish nursing home residents. Cronbach's alpha reliability analysis was performed to determine internal consistency.

Association between metabolic syndrome and risk of both prevalent and incident frailty in older adults: Findings from The Irish Longitudinal Study on Ageing (TILDA).

Objectives: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease, diabetes, and all-cause mortality. Frailty is a condition of decreased multi-system physiological reserve where one has increased vulnerability to stressors. This study aimed to examine if MetS is associated with prevalent and incident frailty over a 4-year follow-up period in an aged population.

TB screening, prevention and treatment cascade in a Malawi prison.

Incarcerated individuals, especially in high HIV and TB burden settings, are at increased risk of latent TB infection and/or TB disease. We implemented a comprehensive HIV-TB intervention in a Malawi prison and studied its feasibility. Between February and December 2019, consenting individuals underwent screening for HIV, TB infection and TB disease.

An examination of the prevalence of metabolic syndrome in older adults in Ireland: Findings from The Irish Longitudinal Study on Ageing (TILDA).

Metabolic syndrome (MetS) consists of the cluster of central obesity, insulin resistance, hypertension and atherogenic dyslipidaemia. It is a risk factor for cardiovascular disease, diabetes, and mortality. The prevalence of MetS has not been described in older adults from a population-representative sample in a European country before.

The HIV cascade of care among serodiscordant couples in four high HIV prevalence settings in sub-Saharan Africa.

Background:  HIV-serodiscordant couples are at high risk of HIV transmission. In sub-Saharan Africa, HIV-serodiscordant couples contribute ~30% of all new infections in the region.

Objectives: To quantify the prevalence of HIV-serodiscordant couples and evaluate steps of the HIV cascade of care among people living with HIV in serodiscordant relationships in four high-prevalence settings in sub-Saharan Africa.

Efficient DNA Condensation Induced by Chiral β-Amino Acid-Based Cationic Surfactants.

Four cationic chiral amino acid-based surfactants, - and - and - and -, have been studied as DNA-condensing agents with enhanced properties and the absence of cell toxicity. The polar head of the surfactant is made of a cyclobutane β-amino acid in which the amino group is a hydrochloride salt and the carboxyl group is involved in an amide bond, allowing the link with hydrophobic C (surfactant ) or C (surfactant ) chains. The ability of these surfactants to condense DNA was investigated using a dye exclusion assay, gel electrophoresis, and circular dichroism and compared with the well-studied dodecyltrimethylammonium bromide (DTAB) and cetyltrimethylammonium bromide (CTAB).

Hybrid Cyclobutane/Proline-Containing Peptidomimetics: The Conformational Constraint Influences Their Cell-Penetration Ability.

A new family of hybrid β,γ-peptidomimetics consisting of a repetitive unit formed by a chiral cyclobutane-containing -β-amino acid plus a -functionalized -γ-amino-l-proline joined in alternation were synthesized and evaluated as cell penetrating peptides (CPP). They lack toxicity on the human tumoral cell line HeLa, with an almost negligible cell uptake. The dodecapeptide showed a substantial microbicidal activity on parasites at 50 µM but with a modest intracellular accumulation.

Carbocycle-Based Organogelators: Influence of Chirality and Structural Features on Their Supramolecular Arrangements and Properties.

The rational design and engineer of organogel-based smart materials and stimuli-responsive materials with tuned properties requires the control of the non-covalent forces driving the hierarchical self-assembly. Chirality, as well as relative configuration, also plays a crucial role promoting the morphology and characteristics of the aggregates. Cycloalkane derivatives can provide chiral chemical platforms allowing the incorporation of functional groups and hydrophobic structural units able for a convenient molecular stacking leading to gels.

Stability, relaxometric and computational studies on Mn complexes with ligands containing a cyclobutane scaffold.

The stability constants of Mn complexes with ligands containing a trans-1,2-cyclobutanediamine spacer functionalized with picolinate and/or carboxylate functions were determined using potentiometric titrations (25 °C, 0.1 M KCl). The stability constant of the complex with a hexadentate ligand containing four acetate groups (L1, log K = 10.

Chiral Cyclobutane-Containing Cell-Penetrating Peptides as Selective Vectors for Anti- Drug Delivery Systems.

Two series of new hybrid γ/γ-peptides, γ-CC and γ-CT, formed by (1,2)-3-amino-2,2,dimethylcyclobutane-1-carboxylic acid joined in alternation to a -functionalized - or -γ-amino-l-proline derivative, respectively, have been synthesized and evaluated as cell penetrating peptides (CPP) and as selective vectors for anti- drug delivery systems (DDS). They lacked cytotoxicity on the tumoral human cell line HeLa with a moderate cell-uptake on these cells. In contrast, both γ-CC and γ-CT tetradecamers were microbicidal on the protozoan parasite beyond 25 μM, with significant intracellular accumulation.

Diagnostic performance and usability of the VISITECT CD4 semi-quantitative test for advanced HIV disease screening.

Background: In sub-Saharan Africa, a third of people starting antiretroviral therapy and majority of patients returning to HIV-care after disengagement, present with advanced HIV disease (ADH), and are at high risk of mortality. Simplified and more affordable point-of-care (POC) diagnostics are required to increase access to prompt CD4 cell count screening for ambulatory and asymptomatic patients. The Visitect CD4 Lateral Flow Assay (LFA) is a disposable POC test, providing a visually interpreted result of above or below 200 CD4cells/mm3.

Gadolinium Complexes of Highly Rigid, Open-Chain Ligands Containing a Cyclobutane Ring in the Backbone: Decreasing Ligand Denticity Might Enhance Kinetic Inertness.

In an effort to explore novel ligand scaffolds for stable and inert lanthanide complexation in magnetic resonance imaging contrast agent research, three chiral ligands containing a highly rigid (1,2)-1,2-cyclobutanediamine spacer and different number of acetate and picolinate groups were efficiently synthesized. Potentiometric studies show comparable thermodynamic stability for the Gd complexes formed with either the octadentate (L3) bearing two acetate or two picolinate groups or the heptadentate (L2) analogue bearing one picolinate and three acetate groups (log = 17.41 and 18.

Cyclobutane-Containing Scaffolds as Useful Intermediates in the Stereoselective Synthesis of Suitable Candidates for Biomedical Purposes: Surfactants, Gelators and Metal Cation Ligands.

Efficient and versatile synthetic methodologies are reported for the preparation of products that are suitable candidates to be used as surfactants, gelators for hydroxylic solvents or metal cation ligands, with potential use in several fields including biomedical applications. The common structural feature of all the synthesized products is the presence of a or -1,2- or -1,3-difunctionalized cyclobutane ring. In the two first cases, the key intermediates including enantiomerically pure 1,3-diamines and 1,3-amino alcohols have been prepared from β-amino acid derivatives obtained, in turn, from a chiral half-ester.

Synthesis and Gelling Abilities of Polyfunctional Cyclohexane-1,2-dicarboxylic Acid Bisamides: Influence of the Hydroxyl Groups.

New enantiomerically pure C-alkyl diamides derived from trihydroxy cyclohexane-1,2-dicarboxylic acid have been synthesized from (-)-shikimic acid. The hydroxyl groups in these compounds are free or, alternatively, they present full or partial protection. Their gelling abilities towards several solvents have been tested and rationalized by means of the combined use of Hansen solubility parameters, scanning electron microscopy (SEM), and circular dichroism (CD), as well as computational calculations.

Cyclobutane Scaffold in Bolaamphiphiles: Effect of Diastereoisomerism and Regiochemistry on Their Surface Activity Aggregate Structure.

Cationic bolaamphiphiles have been synthesized starting from meso cis- or chiral trans-1,2-difunctionalized cyclobutane derivatives. They include cis/trans pairs of diastereoisomers, of N- or C-centered bisamides. The goal of this work was to investigate the influence of stereochemistry and regiochemistry on their abilities as surfactants and self-assembly.

Stereoselectivity of Proline/Cyclobutane Amino Acid-Containing Peptide Organocatalysts for Asymmetric Aldol Additions: A Rationale.

Several α,β,α- or α,γ,α-tripeptides, consisting of a central cyclobutane β- or γ-amino acid being flanked by two d- or l-proline residues, have been synthesized and tested as organocatalysts in asymmetric aldol additions. High yields and enantioselectivities have been achieved with α,γ,α-tripeptides, being superior to peptides containing a cyclobutane β-amino acid residue. This is probably due to their high rigidity, which hinders some of the peptide catalysts to adopt the proper active conformation.

Studies on Cycloalkane-Based Bisamide Organogelators: A New Example of Stochastic Chiral Symmetry-Breaking Induced by Sonication.

Enantiomerically pure C -alkyl amides derived from cis and trans cycloalkane-1,2-dicarboxylic acids, respectively, have been synthesized and their behavior as organogelators has been investigated. These compounds include cis/trans diastereomeric cyclobutane and cyclohexane derivatives with the aim to explore the influence of the ring size as well as the relative configuration in their hierarchical self-assembly to form gels. High resolution H NMR spectroscopy studies allowed the determination of the dynamics of the gelation process in [D ]toluene and the sol-gel transition temperature.

Chiral Cyclobutane β-Amino Acid-Based Amphiphiles: Influence of Cis/Trans Stereochemistry on Condensed Phase and Monolayer Structure.

New diastereomeric nonionic amphiphiles, cis- and trans-1, based on an optically pure cyclobutane β-amino ester moiety have been investigated to gain insight into the influence exerted by cis/trans stereochemistry and stereochemical constraints on the physicochemical behavior, molecular organization, and morphology of their Langmuir monolayers and dry solid states. All these features are relevant to the rational design of functional materials. trans-1 showed a higher thermal stability than cis-1.

Chiral Cyclobutane β-Amino Acid-Based Amphiphiles: Influence of Cis/Trans Stereochemistry on Solution Self-Aggregation and Recognition.

Novel diastereomeric anionic amphiphiles based on the rigid cyclobutane β-amino acid scaffold have been synthesized and deeply investigated with the aim of generating new functional supramolecular architectures on the basis of the rational design of original amphiphilic molecules and the control of their self-assembly. The main interest has been focused on the effect that cis/trans stereochemistry exerts on their molecular organization and recognition. In diluted solutions, the relative stereochemistry mainly influences the headgroup solvation and anionic-charge stabilization, i.