Validating human induced pluripotent stem cell-specific quality control tests for the release of an intermediate drug product in a Good Manufacturing Practice quality system.

One of the challenges in Good Manufacturing Practice (GMP)-compliant human induced pluripotent stem cell (hiPSC) production is the validation of quality control (QC) tests specific for hiPSCs, which are required for GMP batch release. This study presents a comprehensive description of the validation process for hiPSC-specific GMP-compliant QC assays; more specifically, the validation of assays to assess the potential presence of residual episomal vectors (REVs), the expression of markers of the undifferentiated state and the directed differentiation potential of hiPSCs. Critical aspects and specific acceptance criteria were formulated in a validation plan prior to assay validation. Assay specificity, sensitivity and reproducibility were tested, and the equipment used for each assay was subjected to performance qualification. A minimum input of 20 000 cells (120 ng of genomic DNA) was defined for accurate determination of the presence of REVs. Furthermore, since vector loss in hiPSC lines is a passage-dependent process, we advocate screening for REVs between passages eight and 10, as testing at earlier passages might lead to unnecessary rejection of hiPSC lines. The cutoff value for assessment of markers of the undifferentiated state was set to the expression of at least three individual markers on at least 75% of the cells. When multi-color flow cytometry panels are used, a fluorescence minus one control is advised to ensure the control for fluorescent spread. For the assay to assess the directed differentiation potential, the detection limit was set to two of three positive lineage-specific markers for each of the three individual germ layers. All of our assays proved to be reproducible and specific. Our data demonstrate that our implemented analytical procedures are suitable as QC assays for the batch release of GMP-compliant hiPSCs.

Good Manufacturing Practice-compliant human induced pluripotent stem cells: from bench to putative clinical products.

BACKGROUND AIMS: Few human induced pluripotent stem cell (hiPSC) lines are Good Manufacturing Practice (GMP)-compliant, limiting the clinical use of hiPSC-derived products. Here, we addressed this by establishing and validating an in-house platform to produce GMP-compliant hiPSCs that would be appropriate for producing both allogeneic and autologous hiPSC-derived products. METHODS: Our standard research protocol for hiPSCs production was adapted and translated into a GMP-compliant platform. In addition to the generation of GMP-compliant hiPSC, the platform entails the methodology for donor recruitment, consent and screening, donor material procurement, hiPSCs manufacture, in-process control, specific QC test validation, QC testing, product release, hiPSCs storage and stability testing. For platform validation, one test run and three production runs were performed. Highest-quality lines were selected to establish master cell banks (MCBs). RESULTS: Two MCBs were successfully released under GMP conditions. They demonstrated safety (sterility, negative mycoplasma, endotoxins <5.0 EU/mL and negative adventitious agents), cell identity (>75% of cells expressing markers of undifferentiated state, identical STR profile, normal karyotype in >20 metaphases), purity (negative residual vectors and no plasmid integration in the genome) and potency (expression of at least two of the three markers for each of the three germ layers). In addition, directed differentiation to somitoids (skeletal muscle precursors) and six potential clinical products from all three germ layers was achieved: pancreatic islets (endoderm), kidney organoids and cardiomyocytes (mesoderm), and keratinocytes, GABAergic interneurons and inner-ear organoids (ectoderm). CONCLUSIONS: We successfully developed and validated a platform for generating GMP-compliant hiPSC lines. The two MCBs released were shown to differentiate into clinical products relevant for our own and other regenerative medicine interests.

Satellite ligand effects on magnetic exchange in dimers. A structural, magnetic and theoretical investigation of Cu2L2X4 (L = methylisothiazolinone and X = Cl-, Br-).

Halide-bridged polymers have gained significant interest due to their diverse properties and potential applications. Stacked Cu2L2X4 dimers, where L is an organic ligand and X can be Cl- or Br-, are of interest because a chloride analogue where L = 2-pyridone, had previously been reported to exhibit bulk ferromagnetism, which augured great potentiality for this class of compounds. The synthesis, structural characterization, magnetic susceptibility measurements, and computational studies of two isostructural CuClMI (MI = methylisothiazolinone) and CuBrMI polymers of Cu(II), along with a related CuClPYR (PYR = 2-pyridone) is reported. CuClMI and CuBrMI were found to exhibit AFM bulk properties, due to FM/AFM alternating chains along the halide-bridged polymer axis, while FM bulk properties were confirmed for CuClPYR exhibiting a FM spin ladder. In combination with a benzamide analogue, CuClBA, three O-donor amides, CuClMI, CuClBA and CuClPYR were analyzed and revealed that the kinetic exchange is affected by the identity, but more importantly, the orientation of the satellite ligands. The torsional angle of the ligand with the dimer plane is shown to significantly affect the magnetic exchange in the dimer, and between dimers, explaining the reported FM bulk properties of CuClPYR. This finding is exceedingly important, as it suggests that a spin device can be constructed to flip between singlet/triplet states by manipulating the orientation of the satellite/terminal ligand.

Impact of Transcatheter Device Closure of Atrial Septal Defect on Atrial Arrhythmias Propensity in Young Adults.

Atrial septal defect (ASD) is a condition that requires early intervention because of the consequences over the right-side heart. Chronic atrial stretching promotes atrial conduction delay and the imbalance of the conduction homogeneity, which lead to the propensity to atrial arrhythmias (AA). We aim to evaluate the impact of transcatheter closure of ASD on atrial vulnerability markers leading to late AA in young adults. We conducted a prospective, longitudinal study in one hundred patients (mean age 25.2 ± 5.4 years) who underwent transcatheter closure of ASD at Cardiocentro Pediátrico William Soler. P-wave maximum (Pmax) and P-wave dispersion (Pd) were analyzed from 12-lead electrocardiogram. Left-side and right-side intraatrial and interatrial electromechanical delay (EMD) were measured with tissue Doppler imaging. Both electrocardiographic and echocardiographic analyses were performed during the study period. Compared to baseline, there was a significant reduction in P max (p ≤ 0.001) and Pd (p ≤ 0.001) after 3 months of procedure. All atrial electromechanical coupling parameters significantly reduced at 6 months of ASD closure and tend to remain at lower values till the last evaluation. Over 9.2 ± 1.6 years of follow-up, 15 subjects (15%) developed AA, of which intraatrial reentrant tachycardia (66.6%) became the main rhythm disturbance. Intra-right atrial EMD ≥ 16 ms (HR 4.08, 95% CI 1.15-14.56; p = 0.03) and Pd 45 ms (HR 1.66, 95% CI 1.06-2.59; p = 0.02) were identified as predictors of late AA. Transcatheter device closure of ASD in young adults promotes a significant reduction of electrocardiographic and echocardiographic markers of AA vulnerability, which persist during the long-term follow-up. Nevertheless, Pd and interatrial EMD were identified as independent risk factors of AA.

Parents' Knowledge, Attitudes, and Experiences in Child Sexual Abuse Prevention in El Salvador.

Childhood sexual abuse (CSA), a global public health problem, is often underreported especially in low-income countries such as El Salvador, and prevention efforts are needed. The purpose of this study was to examine knowledge, attitudes and experiences of CSA prevention and characteristics related to greater knowledge and openness to engaging in child abuse prevention among Salvadoran parents. Salvadoran parents (N = 478) completed questionnaires regarding demographics, definition and signs and symptoms of child abuse, personal experiences of CSA, CSA prevention training, and knowledge, attitudes and practices about preventing CSA. Most parents were knowledgeable about CSA, viewed CSA prevention as their responsibility, and had talked with their children about CSA, although 65.7% incorrectly believed that children are more likely to be abused by strangers. Parents with lower income were less knowledgeable and willing to participate in CSA prevention. CSA programing needs to involve parents and specifically target low-income parents.

The magnetic fingerprint of dithiazolyl-based molecule magnets.

Magnetic bistability in organic-radical based materials has attracted significant interest due to its potential application in electronic devices. The first-principles bottom-up study herein presented aims at elucidating the key factors behind the different magnetic response of the low and high temperature phases of four different switchable dithiazolyl (DTA)-based compounds. The drastic change in the magnetic response upon spin transition is always due to the changes in the JAB magnetic interactions between adjacent radicals along the π-stacks of the crystal, which in turn are driven mostly by the changes in the interplanar distance and degree of lateral slippage, according to the interpretation of a series of magneto-structural correlation maps. Furthermore, specific geometrical dispositions have been recognized as a ferromagnetic fingerprint in such correlations. Our results thus show that an appropriate substitution of the chemical skeleton attached to the DTA ring could give rise to new organic materials with dominant ferromagnetic interactions.

Origin of Bistability in the Butyl-Substituted Spirobiphenalenyl-Based Neutral Radical Material.

One of the most remarkable bistable materials reported so far is made of π dimers of a butyl-substituted spirobiphenalenyl boron radical (butyl-SBP). The phase transition of this material, which is accompanied by changes in its optical, conductive, and magnetic properties, occurs with a hysteretic loop 25 K wide centered at 335 K. Herein, a computational study is presented aimed at deciphering the origin of this hysteresis. The phase transition of butyl-SBP consists of a spin transition of the constituent π dimers coupled with an order-disorder transition involving the butyl chains linked to the nitrogen atoms of the superimposed phenalenyl rings of the π dimer. Below 335 K, the terminal methyl group of the butyl chains adopts a gauche conformation with respect to the methylene unit bonded to the nitrogen atom. Above 335 K, the methyl group is in an anti conformation and exhibits dynamic disorder. The gauche→anti conformational rearrangement triggers the spin transition of the π dimers and is responsible for the hysteretic behavior of butyl-SBP. Specifically, the onset of the phase transition in the heating mode, and thus, the width of the hysteresis loop, are governed by the high energy cost and strong structural cooperative effects associated with this conformational change. Our results show that coupling a spin switch with a conformational switch in a molecular crystal provides a promising strategy in the design of new bistable materials.

Bistability in Organic Magnetic Materials: A Comparative Study of the Key Differences between Hysteretic and Non-hysteretic Spin Transitions in Dithiazolyl Radicals.

Dithiazolyl (DTA)-based radicals have furnished many examples of organic spin-transition materials, some of them occurring with hysteresis and some others without. Herein, we present a combined computational and experimental study aimed at deciphering the factors controlling the existence or absence of hysteresis by comparing the phase transitions of 4-cyanobenzo-1,3,2-dithiazolyl and 1,3,5-trithia-2,4,6-triazapentalenyl radicals, which are prototypical examples of non-bistable and bistable spin transitions, respectively. Both materials present low-temperature diamagnetic and high-temperature paramagnetic structures, characterized by dimerized (⋅⋅⋅A-A⋅⋅⋅A-A⋅⋅⋅)n and regular (⋅⋅⋅A⋅⋅⋅A⋅⋅⋅A⋅⋅⋅A⋅⋅⋅)n π-stacks of radicals, respectively. We show that the regular π-stacks are not potential energy minima but average structures arising from a dynamic inter-conversion between two degenerate dimerized configurations: (⋅⋅⋅A-A⋅⋅⋅A-A⋅⋅⋅)n ↔(-A⋅⋅⋅A-A⋅⋅⋅A-)n . The emergence of this intra-stack dynamics upon heating gives rise to a second-order phase transition that is responsible for the change in the dominant magnetic interactions of the system. This suggests that the promotion of a (⋅⋅⋅A-A⋅⋅⋅A-A⋅⋅⋅)n ↔(-A⋅⋅⋅A-A⋅⋅⋅A-)n dynamics is a general mechanism for triggering spin transitions in DTA-based materials. Yet, this intra-stack dynamics does not suffice to generate bistability, which also requires a rearrangement of the intermolecular bonds between the π-stacks via a first-order phase transition.

Ferromagnetic Exchange in Bichloride Bridged Cu(II) Chains: Magnetostructural Correlations between Ordered and Disordered Systems.

The synthesis, structure, magnetic properties, and theoretical analysis of a new phase of dichloro(2-chloro-3-methylpyridine)copper(II) (2) and its isomorphous analogue dichloro(2-bromo-3-methylpyridine)copper(II) (3) are reported. Both complexes crystallize in the orthorhombic space group Pbca and present square pyramidal Cu(II) ions bridged into chains by chloride ions with each copper(II) bearing a single pyridine ligand. Variable temperature magnetic susceptibility measurements were well fit by a uniform one-dimensional ferromagnetic chain model with 2, J = 69.0(7) K, C = 0.487 emu-K/mol-Oe; 3, J = 73.9(4) K, C = 0.463 emu-K/mol-Oe (H = -JΣSi·Sj Hamiltonian). The experimental J-values were confirmed via theoretical calculations. Comparison to a known disordered polymorph of dichloro(2-chloro-3-methylpyridine)copper(II), 1, shows marked differences as there are significant antiferromagnetic next-nearest neighbor interactions in 1 in addition to randomness induced by the disorder which provide a distinctly different magnetic response. The differences in magnetic behavior are attributed principally to the structural difference in the Cu(II) coordination sphere, 1 being significantly closer to trigonal-bipyramidal, whose difference changes both the nearest and next-nearest neighbor interactions.

Understanding room-temperature π-dimerisation of radical ions: intramolecular π-[TTF]22+ in functionalised calix[4]arenes.

Long, multicentre π-dimers of radical ions are weakly bound and can only be observed in solution at low temperature. However, recent supramolecular approaches induce the extra stabilisation required to preserve them at room temperature, by different means depending on the approach. In particular, π-[TTF]22+ dimers (TTF = tetrathiafulvalene) were detected upon oxidation of a TTF-based calix[4]arene in acetonitrile solution at room temperature, manifesting intramolecular [R-TTF]˙+[R-TTF]˙+ interactions (Chem. Commun. 2006, 2, 2233). In this work, the reasons behind the remarkable formation of these π-dimers in the calix[4]arene, [calix], molecule are unravelled by means of DFT calculations. We first demonstrate that the properties of the π-[R-TTF]22+ dimers are preserved in the [calix]2+. Most importantly, our results show that the π-dimerised and non-dimerised forms of the [calix]2+ are isoenergetic at room temperature, and that the activation energy for this process is ca. 9.5 kcal mol-1. Hence, both forms coexist in equilibrium at 298 K, as the intramolecular nature of the interaction ensures a high reaction rate. The role of the Na+ cation in preventing the π-[R-TTF]22+ dimerisation of the [calix]2+ receptor is also examined, unveiling that this effect is mostly due to the electrostatic repulsion induced by the cation. Finally, we provide a revision on room-temperature stable supramolecular long, multicentre π-dimers of radical ions, a class of systems with great potential as molecular switches.

Examination of the Phenomenology and Clinical Correlates of Emetophobia in a Sample of Salvadorian Youths.

Emetophobia is an under-researched disorder characterized by a specific fear of vomiting. There is a paucity of research on this impairing condition, with extant examinations being largely limited to adult samples and online communities. The present study examined the incidence, phenomenology, and correlates of emetophobia in 305 Salvadorian youths. Caregivers completed a battery of questionnaires regarding the youth's symptoms of emetophobia, internalizing/externalizing symptoms, health anxiety, and obsessive-compulsive symptoms. Approximately 7.5 % of the sample was elevated on emetophobia symptoms, and higher levels of emetophobia symptoms were correlated with higher levels of internalizing, externalizing, health anxiety, and obsessive-compulsive symptoms, and lower levels of adaptive functioning. Youths meeting the cutoff for elevated emetophobia symptoms versus those who did not demonstrated significantly higher levels of externalizing behaviors, as well as general obsessive-compulsive symptoms, especially doubting/checking and neutralizing behaviors. These findings are hoped to help improve the conceptualization and treatment of this poorly understood disorder.

Formation of Long, Multicenter π-[TCNE]22- Dimers in Solution: Solvation and Stability Assessed through Molecular Dynamics Simulations.

Purely organic radical ions dimerize in solution at low temperature, forming long, multicenter bonds, despite the metastability of the isolated dimers. Here, we present the first computational study of these π-dimers in solution, with explicit consideration of solvent molecules and finite temperature effects. By means of force-field and ab initio molecular dynamics and free energy simulations, the structure and stability of π-[TCNE]22- (TCNE=tetracyanoethylene) dimers in dichloromethane have been evaluated. Although the dimers dissociate at room temperature, they are stable at 175 K and their structure is similar to the one in the solid state, with a cofacial arrangement of the radicals at an interplanar separation of approximately 3.0 Å. The π-[TCNE]22- dimers form dissociated ion pairs with the NBu4+ counterions, and their first solvation shell comprises approximately 20 CH2 Cl2 molecules. Among them, the eight molecules distributed along the equatorial plane of the dimer play a key role in stabilizing the dimer through bridging C-H⋅⋅⋅N contacts. The calculated free energy of dimerization of TCNE.- in solution at 175 K is -5.5 kcal mol-1 . These results provide the first quantitative model describing the pairing of radical ions in solution, and demonstrate the key role of solvation forces on the dimerization process.

The Tetracyanopyridinide Dimer Dianion, σ-[TCNPy]2 (2.).

The reaction of 2,3,5,6-tetracyanopyridine (TCNPy) and Cr(C6 H6 )2 forms diamagnetic σ-[TCNPy]2 (2-) possessing a 1.572(3) Šintrafragment sp(3) -sp(3) bond. This is in contrast to the structurally related 1,2,4,5-tetracyanobenzene and 1,2,4,5-tetracyanopyrazine that form π-dimer dianions possessing long, multicenter bonds.

Unravelling the Key Driving Forces of the Spin Transition in π-Dimers of Spiro-biphenalenyl-Based Radicals.

Spiro-biphenalenyl (SBP) boron radicals constitute an important family of molecules for the preparation of functional organic materials. The building blocks of several SBP-based crystals are π-dimers of these radicals, in which two phenalenyl (PLY) rings face each other and the other two PLYs point away from the superimposed PLYs. The dimers of ethyl-SBP and butyl-SBP undergo a spin transition between a diamagnetic and a paramagnetic state upon heating, while other dimers exhibit paramagnetism at all temperatures. Here, we present a computational study aimed at establishing the driving forces of the spin-transition undergone by ethyl-SBP at ∼140 K. The ground state of the π-dimers below 140 K is a singlet state in which the SBP unpaired electrons are partially localized in the superimposed PLYs. Above 140 K, the unpaired electrons are localized in the nonsuperimposed PLYs. These high-temperature structures are exclusively governed by the ground triplet state because the open-shell singlet with the unpaired electrons localized in the nonsuperimposed PLYs does not feature any minimum in the potential energy surface of the system. Furthermore, we show that the electrostatic component of the interaction energy between SBP radicals in the π-dimers is more attractive in the triplet than in the singlet, thereby partially counteracting the bonding and dispersion components, which favor the singlet. This electrostatic stabilization of the triplet state is a key driving force of the spin transition of ethyl-SBP and a key factor explaining the paramagnetic response of the π-dimers of other SBP-based crystals.

Orientational preference of long, multicenter bonds in radical anion dimers: a case study of π-[TCNB]2 (2-) and π-[TCNP]2 (2.).

The similar shape and electronic structure of the radical anions of 1,2,4,5-tetracyanopyrazine (TCNP) and 1,2,4,5-tetracyanobenzene (TCNB) suggest a similar relative orientation for their long, multicenter carbon-carbon bond in π-[TCNP]2 (2-) and in π-[TCNB]2 (2-) , in good accord with the Maximin Principle predictions. Instead, the two known structures of π-[TCNP]2 (2-) have a D2h (θ=0°) and a C2 (θ=30°) orientation (θ being the dihedral angle that determines the rotation of one radical anion relative to the other along the axis that passes through center of the two six-membered rings). The only known π-[TCNB]2 (2-) structure has a C2 (θ=60°) orientation. The origin of these preferences was investigated for both dimers by computing (at the RASPT2/RASSCF(30,28) level) the variation with θ of the interaction energy (Eint ) and the variation of the Eint components. It was found that: 1) a long, multicenter bond exists for all orientations; 2) the Eint (θ) angular dependence is similar in both dimers; 3) for all orientations the electrostatic component dominates the value of Eint (θ), although the dispersion and bonding components also play a relevant role; and 4) the Maximin Principle curve reproduces well the shape of the Eint (θ) curve for isolated dimers, although none of them reproduce the experimental preferences. Only after the (radical anion)(.-) ⋅⋅⋅cation(+) interactions are also included in the model aggregate are the experimental data reproduced computationally.

A New Conformation With an Extraordinarily Long, 3.04†ŠTwo-Electron, Six-Center Bond Observed for the π-[TCNE]2 (2-) Dimer in [NMe4 ]2 [TCNE]2 (TCNE=Tetracyanoethylene).

Invited for the cover of this issue are the groups of Joel S. Miller at the University of Utah and Juan J. Novoa at the University of Barcelona. The image depicts a visualization of the energy difference between the new 2e(-) /6c and the established 2e(-) /4c bond for C2 and D2h conformations, respectively, for π-[TCNE]2 (2-) . Read the full text of the article at 10.1002/chem.201501963.

A New Conformation With an Extraordinarily Long, 3.04†ŠTwo-Electron, Six-Center Bond Observed for the π-[TCNE]2 (2-) Dimer in [NMe4 ]2 [TCNE]2 (TCNE=Tetracyanoethylene).

[NMe4 ]2 [TCNE]2 (TCNE=tetracyanoethenide) formed from the reaction of TCNE and (NMe4 )CN in MeCN has νCN IR absorptions at 2195, 2191, 2172, and 2156 cm(-1) and a νCC absorption at 1383 cm(-1) that are characteristic of reduced TCNE. The TCNEs have an average central CC distance of 1.423 Šthat is also characteristic of reduced TCNE. The reduced TCNE forms a previously unknown non-eclipsed, centrosymmetric π-[TCNE]2 (2-) dimer with nominal C2 symmetry, 12 sub van der Waals interatomic contacts <3.3 Å, a central intradimer separation of 3.039(3) Å, and comparable intradimer C⋅⋅⋅N distances of 3.050(3) and 2.984(3) Å. The two pairs of central C⋅⋅⋅C atoms form a ∢C-C⋅⋅⋅C-C of 112.6° that is substantially greater than the 0° observed for the eclipsed D2h π-[TCNE]2 (2-) dimer possessing a two-electron, four-center (2e(-) /4c) bond with two C⋅⋅⋅C components from a molecular orbital (MO) analysis. A MO study combining CAS(2,2)/MRMP2/cc-pVTZ and atoms-in-molecules (AIM) calculations indicates that the non-eclipsed, C2 π-[TCNE]2 (2-) dimer exhibits a new type of a long, intradimer bond involving one strong C⋅⋅⋅C and two weak C⋅⋅⋅N components, that is, a 2e(-) /6c bond. The C2 π-[TCNE]2 (2-) conformer has a singlet, diamagnetic ground state with a thermally populated triplet excited state with J/kB =1000 K (700 cm(-1) ; 86.8 meV; 2.00 kcal mol(-1) ; H=-2 JSa ⋅Sb ); at the CAS(2,2)/MBMP2 level the triplet is computed to be 9.0 kcal mol(-1) higher in energy than the closed-shell singlet ground state. The results from CAS(2,2)/NEVPT2/cc-pVTZ calculations indicate that the C2 and D2h conformers have two different local metastable minima with the C2 conformer being 1.3 kcal mol(-1) less stable. The different natures of the C2 and D2h conformers are also noted from the results of valence bond (VB) qualitative diagram that shows a 10e(-) /6c bond with one C⋅⋅⋅C and two C⋅⋅⋅N bonding components for the C2 conformer as compared to the 6e(-) /4c bond for the D2h conformer with two C⋅⋅⋅C bonding components.

The origin of the room-temperature stability of [TTF]˙⁺⋠⋠⋠[TTF]˙⁺ long, multicenter bonds found in functionalized π-[R-TTF]2²âº dimers included in the cucurbit[8]uril cavity.

A computational study is performed to identify the origin of the room-temperature stability, in aqueous solution, of functionalized π-[R-TTF]2(2+) dimers (TTF=tetrathiafulvalene; R=(CH2OCH2)5CH2OH) included in the cavity of a cucurbit[8]uril (CB[8]) molecule. π-[R-TTF]2(2+) dimers in pure water are weakly stable, and are mostly dissociated at room temperature. Upon addition of CB[8] to an aqueous π-[R-TTF]2(2+) solution, a (π-[R-TTF]2⊂CB[8])(2+) inclusion complex is formed. The same complex is obtained after the sequential inclusion of two [R-TTF](.+) monomers in the CB[8] molecule. Both processes are thermodynamically and kinetically allowed. π-[R-TTF]2(2+) dimers dissolved in pure water present a [TTF](.+)⋅⋅⋅[TTF](.+) long, multicenter bond, similar to that already identified in π-[TTF]2(2+) dimers dissolved in organic solvents. Upon their inclusion in CB[8], the strength and other features of the [TTF](.+)⋅⋅⋅[TTF](.+) long, multicenter bond are preserved. The room temperature stability of the π-[R-TTF]2(2+) dimers included in CB[8] is shown to originate in the π-[R-TTF]2(2+)⋅⋅⋅CB[8] interaction, the strength of which comes from a strongly attractive electrostatic component and a dispersion component. Such a dominant electrostatic term is caused by the strongly polarized charge distribution in CB[8], the geometrical complementarity of the π-[R-TTF]2(2+) and CB[8] geometries, and the amplifying effect of the 2+ charge in π-[R-TTF]2(2+).

Elucidating the 2D magnetic topology of the 'metal-radical' TTTA⋠Cu(hfac)2 system.

The TTTA⋅Cu(hfac)2 polymer (1; in which TTTA = 1,3,5-trithia-2,4,6-triazapentalenyl, and hfac = (1,1,1,5,5,5)-hexafluoroacetylacetonate) is one of the most prominent examples of the rational use of the 'metal-radical' synthetic approach to achieve ferromagnetic interactions. Experimentally, the magnetic topology of 1 could not be fully deciphered. Herein, the first-principles bottom-up procedure was applied to elucidate the nature and strength of the magnetic JAB exchange interactions present in 1. The computed JAB values give rise to a 2D magnetic topology of ferromagnetic dimers (+11.9 cm(-1)) coupled through weaker antiferromagnetic interactions (-3.0 and -3.2 cm(-1)) in two different spatial directions. The hitherto unknown origin of the antiferromagnetic interdimer interactions is thus unveiled. By using the 2D magnetic topology, the agreement between calculated and experimental χT(T) data is extraordinary. In the metal-radical TTTA⋅Cu(hfac)2 compound, the computational model transcends the local dimer cluster model owing to strong interactions between metal centers and organic radicals, thereby creating a de facto biradical. In addition, it is shown that the magnetic topology cannot be inferred from the polymeric [TTTA⋅⋅⋅Cu(hfac)2]n crystal motif, that is, from its chemical coordination pattern. Instead, one should think in terms of magnetic building blocks, namely, the de facto biradicals.

S=1/2 one-dimensional random-exchange ferromagnetic zigzag ladder, which exhibits competing interactions in a critical regime.

The synthesis, crystal structure, and magnetic properties (from a combined experimental and First-Principles Bottom-Up theoretical study) of the new compound catena-dichloro(2-Cl-3Mpy)copper(II), 1, [2-Cl-3Mpy=2-chloro-3-methylpyridine] are described and rationalized. Crystals of 1 present well isolated magnetic 1D chains (no 3D order was experimentally observed down to 1.8 K) and magnetic frustration stemming from competing ferromagnetic nearest-neighbor (J(NN)) interactions and antiferromagnetic next-nearest neighbor (J(NNN)) interactions, in which α=J(NNN)/J(NN) <-0.25. These magnetic interactions give rise to a unique magnetic topology: a two-leg zigzag ladder composed of edge-sharing up-down triangles with antiferromagnetic interactions along the rails and ferromagnetic interactions along the zigzag chain that connects the rails. Crystals of 1 also present a random distribution of the 2-Cl-3Mpy groups, which are arranged in two different orientations, each with a 50 % occupancy. This translates into a random static structural disorder within each chain by virtue of which the value of the J(NN) magnetic interactions can randomly take one of the following three values: 53, 36, and 16 cm(-1). The structural disorder does not affect the J(NNN) value, which in all cases is approximately -9 cm(-1). A proper statistical treatment of this disorder provides a computed magnetic susceptibility curve that reproduces the main features of the experimental data.