Spectroscopic and thermodynamic characterization of a cobalt-verdazyl valence tautomeric system. influence of crystal structure, solvent and counterion.

Crystallization of the verdazyl-based valence tautomeric ion [Co(dipyvd)2]2+ (where dipyvd is the radical ligand 1-isopropyl-3,5-di(2'-pyridyl)-6-oxoverdazyl) with a variety of different counterions results in materials that show varying degrees of valence tautomeric (VT) transition in the solid state. The X-ray structure of the SbF6 salt at 150 K reveals a localized structure for the S = 1/2 tautomer, with a Co3+ cation and distinct anionic and radical ligands. Comparison with the structure of the same material at 300 K reveals large structural changes in the ligand as a result of the valence tautomeric equilibrium. Data for the S = 3/2 form is less conclusive; X-ray spectroscopy on the PF6 salt suggests a degree of low spin Co2+ character for the S = 3/2 tautomer at very low temperature though this is inconsistent with EPR data at similar temperatures and structural information at 150 K. Magnetic measurements on the [BArF4]- and triflate salts in organic solvents show that the VT equilibrium is dependent on solvent and ion pairing effects.

Metal-ligand interactions in a redox active ligand system. Electrochemistry and spectroscopy of [M(dipyvd)2]n+ (M=Zn, Ni, n=0, 1, 2).

Reaction of nickel and zinc triflates with the tridentate leucoverdazyl 1-isopropyl-3,5-di (2'-pyridyl)-6-oxo-2H-tetrazine (dipyvdH) and triethylamine resulted in the neutral coordination compounds M(dipyvd)2 (M = Ni,Zn). In acetonitrile, both compounds undergo two one electron oxidation processes, Zn (dipyvd)2 at -0.28 V and -0.12 V and Ni(dipyvd)2 at -0.32 V and -0.15 V vs ferrocene/ferricenium. Oxidations are ligand based resulting in an intermediate mixed valence species and a cationic bis(verdazyl) compound respectively. Oxidation of the ligand changes a localized, antiaromatic, non-planar 8π electron anion to a planar, delocalized 7π electron radical. The change in ligand structure results in an increase in the octahedral ligand field splitting from 10,500 cm-1 to ∼13,000 cm-1, suggesting an increase in the pi acceptor character of the ligand. In the mixed valence species, spectroscopic data suggests minimal interaction between ligands mediated by the metal center; i.e., these are class I-II systems in the Robin-Day classification.

Modifications of Tanabe-Sugano d6 Diagram Induced by Radical Ligand Field: Ab Initio Inspection of a Fe(II)-Verdazyl Molecular Complex.

Quantum entanglement between the spin states of a metal center and radical ligands is suggested in an iron(II) [Fe(dipyvd)2]2+ compound (dipyvd = 1-isopropyl-3,5-dipyridil-6-oxoverdazyl). Wave function ab initio (Difference Dedicated Configuration Interaction, DDCI) inspections were carried out to stress the versatility of local spin states. We named this phenomenon excited state spinmerism, in reference to our previous work (see Roseiro et al., ChemPhysChem 2022, e202200478) where we introduced the concept of spinmerism as an extension of mesomerism to spin degrees of freedom. The construction of localized molecular orbitals allows for a reading of the wave functions and projections onto the local spin states. The low-energy spectrum is well-depicted by a Heisenberg picture. A 60 cm-1 ferromagnetic interaction is calculated between the radical ligands with the Stotal = 0 and 1 states largely dominated by a local low-spin SFe = 0. In contrast, the higher-lying Stotal = 2 states are superpositions of the local SFe = 1 (17%, 62%) and SFe = 2 (72%, 21%) spin states. Such mixing extends the traditional picture of a high-field d6 Tanabe-Sugano diagram. Even in the absence of spin-orbit coupling, the avoided crossing between different local spin states is triggered by the field generated by radical ligands. This puzzling scenario emerges from versatile local spin states in compounds which extend the traditional views in molecular magnetism.

Rare variants in KDR, encoding VEGF Receptor 2, are associated with tetralogy of Fallot.

PURPOSE: Rare genetic variants in KDR, encoding the vascular endothelial growth factor receptor 2 (VEGFR2), have been reported in patients with tetralogy of Fallot (TOF). However, their role in disease causality and pathogenesis remains unclear. METHODS: We conducted exome sequencing in a familial case of TOF and large-scale genetic studies, including burden testing, in >1,500 patients with TOF. We studied gene-targeted mice and conducted cell-based assays to explore the role of KDR genetic variation in the etiology of TOF. RESULTS: Exome sequencing in a family with two siblings affected by TOF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants. Rare variant burden analysis conducted in a set of 1,569 patients of European descent with TOF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 × 10-11). CONCLUSION: Rare KDR variants, in particular PTVs, strongly associate with TOF, likely in the setting of different inheritance patterns. Supported by genetic and in vivo and in vitro functional analysis, we propose loss-of-function of VEGFR2 as one of the mechanisms involved in the pathogenesis of TOF.

Developmental Trajectories of Religious Service Attendance: Predictors of Nicotine Dependence and Alcohol Dependence/Abuse in Early Midlife.

This longitudinal study assesses the associations between developmental trajectories of religious service attendance from mean age 14 to mean age 43 and nicotine dependence and alcohol dependence/abuse at mean age 43 (N = 548). Six trajectories of religious service attendance were identified. As compared with belonging to weekly stable trajectory group, a higher probability of belonging to the weekly/none decreasing, occasional stable, and non-attendance trajectory group was significantly associated with a higher likelihood of nicotine dependence. In addition, as compared with belonging to weekly stable trajectory group, a higher probability of belonging to the weekly/none decreasing, weekly/occasional decreasing, occasional stable, and non-attendance trajectory group was significantly associated with a higher likelihood of alcohol dependence/abuse. These findings are consistent with the hypothesis that religious service attendance protects against nicotine dependence and alcohol dependence/abuse in early midlife.

Adolescent risk and protective factors predicting triple trajectories of substance use from adolescence into adulthood.

OBJECTIVES: Since the number of individuals who use substances in the United States has markedly increased every year, substance use is a significant public health concern. The current study examines the possible risk and protective factors associated with triple comorbid trajectories of longitudinal alcohol, tobacco, and cannabis use from age 14 to 36. METHODS: A community sample of 674 participants (53% African Americans and 47% Puerto Ricans; 60% females) were recruited from the Harlem Longitudinal Development Study. Multinomial logistic regression analyses were conducted to examine the associations between the risk (low self-control, peer drug use) and protective (parent-child attachment, family church attendance) factors at age 14 and membership in the triple trajectory groups derived from a multivariate growth mixture model. RESULTS: Low self-control and peer drug use were associated with an increased likelihood of being a member in the triple comorbid trajectory groups compared to the reference group (i.e., low alcohol, no tobacco, and no cannabis use). On the other hand, parent-child attachment and family church attendance were associated with a decreased likelihood of being a member in the triple comorbid trajectory groups compared to the reference group. CONCLUSIONS: Treatment programs for adolescents who use substances may be more helpful if their parents and/or friends could also participate together with the adolescent, rather than only the adolescent participates in the treatment programs. Further research is needed to gain a greater understanding of the conceptual nature of the relationship between earlier risk and protective factors and later substance use patterns.

Valence tautomerism in a cobalt-verdazyl coordination compound.

Coordination of 1-isopropyl-3,5-dipyridyl-6-oxoverdazyl to cobalt results in a dication best described in the solid state as a high spin cobalt(ii) ion coordinated to two radical ligands with an S = 3/2 ground state. On dissolution in acetonitrile, the cobalt(ii) form equilibrates with a cobalt(iii) valence tautomer with an S = 1/2 ground state.

Longitudinal Smoking Patterns: Do They Predict Symptoms of ADHD in Adults?

Objective: The objective of this study was to assess whether comparisons of longitudinal smoking trajectories predict differences in symptoms of ADHD in adults. Method: Participants were interviewed 7 times between 14 and 43 years of age. ADHD symptoms at outcome were assessed with the World Health Organization ADHD Self-Report Scale. Bivariate and multivariate linear regression analyses assessed the associations between the trajectories of smoking and ADHD symptoms. Results: The multivariate analysis (R2 = .12) indicated that compared with being nonsmokers, the probability of being in the heavy/continuous group (standardized regression coefficient [SRC] = .17, p < .01) and in the late starter group (SRC = .11, p < .05) were significantly associated with adult ADHD symptoms. Conclusion: Longitudinal smoking patterns were associated with ADHD symptoms in adults. Chronic smoking jeopardizes both physical health and the ability to fulfill adult roles as employees, family members, and friends. Smoking cessation in adolescence may lessen the likelihood of ADHD symptoms in adulthood.

Long-range spin dependent delocalization promoted by the pseudo Jahn-Teller effect.

Strong spin-dependent delocalization (double exchange) was previously demonstrated for the complexes, NN-Bridge-SQ-Coiii(py)2Cat-Bridge-NN (where NN = S = 12 nitronylnitroxide, Bridge = 1,4-phenylene and single bond, SQ = S = 12 orthobenzosemiquinone, Coiii = low-spin d6 cobalt 3+, and Cat = diamagnetic catecholate). The mixed-valent S = 12 SQ-Coiii-Cat triad results in ferromagnetic alignment of localized (pinned) NN spins which are ∼22 Šapart (Bridge = Ph). Herein, we report similar ferromagnetic coupling of localized verdazyl (Vdz) radical spins. The origin of the magnetic exchange results from a second order vibronic effect (pseudo Jahn-Teller effect) in [Vdz-diox-Ru(py)2-diox-Vdz]0, which possesses a diamagnetic [diox-Ru-diox]0 triad by virtue of strong antiferromagnetic SQ-Ruiii exchange.

Single and dual diagnoses of major depressive disorder and posttraumatic stress disorder predicted by triple comorbid trajectories of tobacco, alcohol, and marijuana use among urban adults.

Background: The adverse consequences of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) affect a significant portion of the US population every year (i.e., 15 million for MDD; 8 million for PTSD) and are of public health concern. The current study examines tobacco, alcohol, and marijuana use as possible longitudinal predictors of MDD and/or PTSD. Methods: A community sample of 674 participants (53% African Americans and 47% Puerto Ricans; 405 females and 269 males) were recruited from the Harlem Longitudinal Development Study. We used Mplus software to obtain the triple trajectories of tobacco, alcohol, and marijuana use from mean age 14 to 36. Logistic regression analyses were then conducted to examine the associations between those triple trajectory groups and a single diagnosis of MDD or PTSD as well as a dual diagnosis of MDD with PTSD at age 36. Results: The observed percentages of MDD, PTSD, and the comorbidity of MDD and PTSD were 17%, 8%, and 5%, respectively. The heavy use of all 3 substances group was associated with an increased likelihood of having MDD (adjusted odds ratio [AOR] = 3.14, P < .01), PTSD (AOR = 3.91, P < .05), and MDD with PTSD (AOR = 6.64, P < .01), as compared with the tobacco and alcohol use group. Conclusions: Treatment programs to quit or reduce the use of tobacco, alcohol, and marijuana may help decrease the prevalence of MDD and PTSD. This could lead to improvements in individualized treatments for patients who use tobacco, alcohol, and marijuana and who have both MDD and PTSD.

Transcriptome alterations in myotonic dystrophy skeletal muscle and heart.

Myotonic dystrophy (dystrophia myotonica, DM) is a multi-systemic disease caused by expanded CTG or CCTG microsatellite repeats. Characterized by symptoms in muscle, heart and central nervous system, among others, it is one of the most variable diseases known. A major pathogenic event in DM is the sequestration of muscleblind-like proteins by CUG or CCUG repeat-containing RNAs transcribed from expanded repeats, and differences in the extent of MBNL sequestration dependent on repeat length and expression level may account for some portion of the variability. However, many other cellular pathways are reported to be perturbed in DM, and the severity of specific disease symptoms varies among individuals. To help understand this variability and facilitate research into DM, we generated 120 RNASeq transcriptomes from skeletal and heart muscle derived from healthy and DM1 biopsies and autopsies. A limited number of DM2 and Duchenne muscular dystrophy samples were also sequenced. We analyzed splicing and gene expression, identified tissue-specific changes in RNA processing and uncovered transcriptome changes strongly correlating with muscle strength. We created a web resource at http://DMseq.org that hosts raw and processed transcriptome data and provides a lightweight, responsive interface that enables browsing of processed data across the genome.

Sexual risk behaviors in African American and Puerto Rican women: Impulsivity and self-control.

Millions of people are living with the human immunodeficiency virus (HIV). African American and Hispanic/Latino communities suffer the most severe burden of HIV in the US. The ultimate goal of this study was to better understand risk factors for this infection: Do impulsivity and self control operate independently or synergistically with respect to HIV sexual risk behaviors in women? An enhanced understanding of these risk factors may better inform future interventions. Among the total of 343 female participants, half were African American and the other half were Latina. Data in this study were collected in the area of New York City during 2014-2016, when the mean age of the participants was 39 years. Linear regression analyses were used to examine the associations of impulsivity and self control with HIV sexual risk behaviors. Impulsivity and self control were independently associated with most of the HIV sexual risk behaviors examined. In addition, the interaction terms between impulsivity and low self control were all significantly associated with each of the sexual risk behaviors. Prevention programs should consider incorporating the roles of impulsivity and self control simultaneously as related to HIV risk behaviors.

Season of birth: A predictor of ADHD symptoms in early midlife.

OBJECTIVE: In this longitudinal study, we applied linear regression analyses to examine season of birth as related to symptoms of attention deficit/hyperactivity disorder (ADHD) in early midlife. METHOD: We gathered longitudinal data on a prospective cohort of community-dwelling men and women (N = 548) followed from adolescence to early midlife. FINDINGS: The findings indicate that, as compared with participants who were born in the summer, those who were born in the spring (Beta = 0.34; t-statistic = 3.59; p < 0.001) had significantly more ADHD symptoms. In addition, exposure to maternal cigarette smoking in adolescence significantly intensified (p < 0.01) the association between season of birth and ADHD symptoms in early midlife. CONCLUSION: These findings suggest that exposure to greater maternal maladaptive behaviors, such as cigarette smoking, may result in a greater vulnerability to other environmental risk factors, such as season of birth.

Correction: An electron transfer driven magnetic switch: ferromagnetic exchange and spin delocalization in iron verdazyl complexes.

Correction for 'An electron transfer driven magnetic switch: ferromagnetic exchange and spin delocalization in iron verdazyl complexes' by David J. R. Brook et al., Dalton Trans., 2018, 47, 6351-6360.

An electron transfer driven magnetic switch: ferromagnetic exchange and spin delocalization in iron verdazyl complexes.

The verdazyl 'pincer' ligand, 1-isopropyl-3,5-dipyridyl-6-oxoverdazyl (dipyvd), coordinates iron to form a series of pseudooctahedral coordination compounds [Fe(dipyvd)2]n+ (n = 0-3). In the case where n = 2, the molecular geometry and physical and spectral properties are consistent with a low spin (S = 0) iron(ii) ion coordinated by two ferromagnetically coupled radical ligands. Upon one electron reduction, the room temperature effective magnetic moment of the complex jumps from µeff = 2.64 to µeff = 5.86 as a result of spin crossover of the iron atom combined with very strong ferromagnetic coupling of the remaining ligand centered unpaired electron with the metal center. The sign of the exchange is opposite to that observed in other high spin iron/radical ligand systems and appears to be a result of delocalization of the ligand unpaired electron across the whole molecule. The large change in magnetic properties, combined with a delocalized electronic structure and accessible redox potentials, suggests the utility of this and related systems in the development of novel molecular spintronic devices.

Verdazyl-ribose: A new radical for solid-state dynamic nuclear polarization at high magnetic field.

Solid-state dynamic nuclear polarization (DNP) using the cross-effect relies on radical pairs whose electron spin resonance (ESR) frequencies differ by the nuclear magnetic resonance (NMR) frequency. We measure the DNP provided by a new water-soluble verdazyl radical, verdazyl-ribose, under both magic-angle spinning (MAS) and static sample conditions at 9.4 T, and compare it to a nitroxide radical, 4-hydroxy-TEMPO. We find that verdazyl-ribose is an effective radical for cross-effect DNP, with the best relative results for a non-spinning sample. Under non-spinning conditions, verdazyl-ribose provides roughly 2× larger 13C cross-polarized (CP) NMR signal than the nitroxide, with similar polarization buildup times, at both 29 K and 76 K. With MAS at 7 kHz and 1.5 W microwave power, the verdazyl-ribose does not provide as much DNP as the nitroxide, with the verdazyl providing less NMR signal and a longer polarization buildup time. When the microwave power is decreased to 30 mW with 5 kHz MAS, the two types of radical are comparable, with the verdazyl-doped sample having a larger NMR signal which compensates for its longer polarization buildup time. We also present electron spin relaxation measurements at Q-band (1.2 T) and ESR lineshapes at 1.2 and 9.4 T. Most notably, the verdazyl radical has a longer T1e than the nitroxide (9.9 ms and 1.3 ms, respectively, at 50 K and 1.2 T). The verdazyl electron spin lineshape is significantly affected by the hyperfine coupling to four 14N nuclei, even at 9.4 T. We also describe 3000-spin calculations to illustrate the DNP potential of possible radical pairs: verdazyl-verdazyl, verdazyl-nitroxide, or nitroxide-nitroxide pairs. These calculations suggest that the verdazyl radical at 9.4 T has a narrower linewidth than optimal for cross-effect DNP using verdazyl-verdazyl pairs. Because of the hyperfine coupling contribution to the electron spin linewidth, this implies that DNP using the verdazyl radical would improve at lower magnetic field. Another conclusion from the calculations is that a verdazyl-nitroxide bi-radical would be expected to be slightly better for cross-effect DNP than the nitroxide-nitroxide bi-radicals commonly used now, assuming the same spin-spin coupling constants.

Trajectories of cannabis use beginning in adolescence associated with symptoms of posttraumatic stress disorder in the mid-thirties.

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms are related to a number of adverse consequences such as substance use and general medical conditions. The present longitudinal study seeks to find the longitudinal patterns of cannabis use as precursors of PTSD symptoms. Such information will serve as a guide for intervention programs for PTSD. METHODS: Growth mixture modeling was conducted to identify the cannabis use trajectory groups using a community sample of 674 participants (53% African Americans, 47% Hispanics of Puerto Rican decent; 60% females) from the Harlem Longitudinal Development Study. Logistic regression analyses were performed to examine the association between earlier trajectories of cannabis use (ages 14 to 36) and later symptoms of PTSD (at age 36) for the full model including the entire sample (N = 674) as well as the reduced model including only participants who had experienced a traumatic event (n = 205). RESULTS: Five trajectory groups of cannabis use were obtained. The chronic use group (full model: adjusted odds ratio [AOR] = 4.68, P < .01; reduced model: AOR = 4.27, P < .05), the late quitting group (full model: AOR = 6.18, P < .01; reduced model: AOR = 6.67, P < .01), and the moderate use group (full model: AOR = 3.97, P < .01; reduced model: AOR = 3.32, P < .05) were all associated with an increased likelihood of having PTSD symptoms at age 36 compared with the no use group. CONCLUSIONS: The findings provide information that PTSD symptoms in the mid-30s can possibly be reduced by decreasing membership in the chronic cannabis use trajectory group, the late quitting trajectory group, and the moderate cannabis use trajectory group.