Mononuclear or Coordination Polymer Complexes? Both Are Possible for 3,6,9-Trioxaundecanedioic Acid.

Investigating the driving forces leading to the formation of a specific supramolecular architecture among a wide spectrum of all the possibly obtainable structures is not an easy task. The contemporary literature provides several models for correctly predicting the thermodynamically accessible structures that can originate from a library of building blocks. Definitions are rigid by their very nature, so their application may sometimes require a shift in perspective. In the study presented herein, we describe the crystal structures of three metallo-supramolecular architectures assembled from deprotonated derivatives of 3,6,9-trioxaundecanedioic acid and Mn(II), Co(II) and Zn(II). In the Mn(II) case, the complexation resulted in a complex of a discrete/heptacoordinated nature, whereas the other two structures appeared as helical polymers. To explain such an anomaly, in this work, we describe how the interplay between the flexibility of the ligand spacer and the number of coordinating atoms involved determines the divergent or convergent organisation of the final coordination architecture.

Intermolecular Forces Driving Hexamethylenetetramine Co-Crystal Formation, a DFT and XRD Analysis.

Interest in co-crystals formation has been constantly growing since their discovery, almost a century ago. Such success is due to the ability to tune the physical-chemical properties of the components in solid state by avoiding a change in their molecular structure. The properties influenced by the co-crystals formation range from an improvement of mechanical features and chemical stability to different solubility. In the scientific research area, the pharmacological field is undoubtedly one of those in which an expansion of the co-crystal knowledge can offer wide benefits. In this work, we described the crystalline structure of hexamethylenetetramine co-crystallized with the isophthalic acid, and we compared it with another co-crystal, showing the same components but different stoichiometry. To give a wider overview on the nature of the interactions behind the observed crystal packing and to rationalize the reasons of its formation, a computational analysis on such structures was carried out.

Do Secondary Electrostatic Interactions Influence Multiple Dihydrogen Bonds? AA-DD Array on an Amine-Borane Aza-Coronand: Theoretical Studies and Synthesis.

Hydrogen bond plays a key role in a wide range of inorganic, organic, as well as biological systems. The understanding on how the chemical environment can affect this kind of interaction is crucial to predict its binding strength and consequently the robustness and the dynamic properties of many supramolecular systems. In this paper a new donor-acceptor complex was synthesized and characterized by SCXRD, showing for the first time in an organic system an AA-DD pattern of a particular hydrogen interaction, called dihydrogen bond. Over 250 functionals were computationally evaluated to select the best method to reproduce the binding interaction geometry of this new pattern. Moreover, a new vector force model was used to split the contribution of primary and secondary electrostatic interactions (SEIs), in order to evaluate how the latter one can modify the binding strength of this unusual hydrogen-hydrogen interaction.

Exploring the Experience and Effects of Vocal Toning.

BACKGROUND: Toning is a form of vocalizing that utilizes the natural voice to express sounds ranging from cries, grunts, and groans to open vowel sounds and humming on the full exhalation of the breath. Music therapists are increasingly utilizing toning in their clinical practice for a variety of therapeutic aims. Yet the effects of toning are not widely understood, with limited research to date. OBJECTIVE: To gather and analyze descriptive data to better understand the experience and effects of self-administered toning. Primary aims were to: 1) understand participants' experiences with toning, and any effects resulting from their experiences; 2) measure participants' emotional response to toning and singing; and 3) examine similarities and differences across the two datasets. METHODS: Participants were 20 adults, ages 20-40 years, who were non-musicians. We conducted semi-structured interviews and used qualitative content analysis to identify major themes and subcategories related to participants' toning experiences. Participants also completed a 48-item questionnaire on music and emotions. Results from the interview and questionnaire data were then compared and contrasted. RESULTS: Results indicate that shifts in attention, awareness, and consciousness frequently occurred when individuals engaged in toning. "Meditative," "calm," and "relaxed" were the three most common descriptors of toning. In contrast, singing evoked stronger emotions and associations than toning, with the three most common descriptors including "nostalgia," "tenderness," and "joyful activation." Findings also suggest that the physical experience with vibrations and the sound of one's own voice may be attributes of toning that likely contribute to its success in inducing altered states of awareness, attention, and consciousness. CONCLUSIONS: This study significantly expands our understanding of the experience and effects of toning, and has direct implications for clinical practice, including the identification of effective strategies to successfully engage adults in toning.

Identification of 2-thioxoimidazolidin-4-one derivatives as novel noncovalent proteasome and immunoproteasome inhibitors.

This paper describes the design, synthesis, and biological evaluation of 2-thioxoimidazolidin-4-one derivatives as inhibitors of proteasome and immunoproteasome, potential targets for the treatment of hematological malignancies. In particular, we focused our efforts on the design of noncovalent inhibitors, which might be a promising therapeutic option potentially devoid of drawbacks and side-effects related to irreversible inhibition. Among all the synthesized compounds, we identified a panel of active inhibitors with Ki values towards one or two chymotrypsin-like activities of proteasome (ß5c) and immunoproteasome (ß5i and ß1i subunits) in the low micromolar range. Docking studies suggested a unique binding mode of the molecules in the catalytic site of immunoproteasome proteolytic subunits.

Long-Term Results of Aortic Root Surgery in Marfan Syndrome Patients: A Single-Center Experience.

BACKGROUND AND AIM OF THE STUDY: The study aim was to compare long-term results of Marfan syndrome (MFS) patients affected by aortic root disease undergoing aortic root replacement with the Bentall or David operation. METHODS: Since 1994, a total of 59 patients has been followed at the authors' Marfan Center, having undergone either a Bentall operation (Bentall group, n = 30) or a David operation (David group, n = 29). RESULTS: No operative mortality was recorded. After 20 years (mean follow up 97 ± 82 months; range 1 to 369 months) no prosthesis-related major bleeding or thromboembolic events had been observed; the 20-year survival was 94 ± 6% in the Bentall group, and 100% in the David group (p = 0.32). Freedom from reintervention for aortic valve dysfunction was 100% in the Bentall group, and 75 ± 13% in the David group (p = 0.04). This inter-group difference became relevant after the first eight-year period of follow-up, and was mainly associated with a particular familiar genetic phenotype involving three out of four reoperated patients. Freedom from all-cause death, myocardial infarction, stroke, prosthetic valve-related complications, and reintervention on any aortic segment was 69 ± 12% in the Bentall group, and 67 ± 14% in the David group (p = 0.33). CONCLUSIONS: The Bentall and David operations are both associated with satisfactory long-term results in MFS patients. The low rate of valve prosthesis-related complications suggested that the Bentall operation would continue to be a standard surgical treatment. The reimplantation technique, adopted for less-dilated aortas, provides satisfactory freedom from reoperation. Careful attention should be paid to the reimplantation technique in patients affected by a serious familiar genetic phenotype.

Improving left spatial neglect through music scale playing.

The study assessed whether the auditory reference provided by a music scale could improve spatial exploration of a standard musical instrument keyboard in right-brain-damaged patients with left spatial neglect. As performing music scales involves the production of predictable successive pitches, the expectation of the subsequent note may facilitate patients to explore a larger extension of space in the left affected side, during the production of music scales from right to left. Eleven right-brain-damaged stroke patients with left spatial neglect, 12 patients without neglect, and 12 age-matched healthy participants played descending scales on a music keyboard. In a counterbalanced design, the participants' exploratory performance was assessed while producing scales in three feedback conditions: With congruent sound, no-sound, or random sound feedback provided by the keyboard. The number of keys played and the timing of key press were recorded. Spatial exploration by patients with left neglect was superior with congruent sound feedback, compared to both Silence and Random sound conditions. Both the congruent and incongruent sound conditions were associated with a greater deceleration in all groups. The frame provided by the music scale improves exploration of the left side of space, contralateral to the right hemisphere, damaged in patients with left neglect. Performing a scale with congruent sounds may trigger at some extent preserved auditory and spatial multisensory representations of successive sounds, thus influencing the time course of space scanning, and ultimately resulting in a more extensive spatial exploration. These findings offer new perspectives also for the rehabilitation of the disorder.

Enhancing Clinicians' Well-Being and Patient-Centered Care Through Mindfulness.

INTRODUCTION: Mindful clinicians are resilient and more likely to provide patient-centered care. We aimed to enhance clinicians' well-being by offering a Mindfulness-Based Stress Reduction (MBSR) course that teaches mindfulness and stress management and then determine whether this impacted their subsequent medical encounters. METHODS: In a longitudinal cohort study with 27 clinicians, MBSR was taught by a certified instructor. Pre-MBSR and post-MBSR online questionnaires assessed burnout, depression, stress, meaningfulness, and mindfulness. Patients independently rated their clinicians using the Rochester Communication Rating Scale (RCRS) after a clinical encounter before and after their clinician took the MBSR course. Nine medical doctors audiorecorded the consultations before and after MBSR; the tapes were coded and analyzed by an independent team using the Roter interaction analyses system. RESULTS: Significant reductions in stress and burnout were found, and increases in mindfulness and meaningfulness. The decrease in stress was correlated with less judgmental attitudes and less reactivity-facets of mindfulness. The decrease in emotional exhaustion was correlated with more acting with awareness and less judgmental attitudes-facets of mindfulness. Patients' perceptions of the clinical encounter suggested that patient-centered care improved after MBSR. Decreased depersonalization was significantly associated with the RCRS subscale, "understanding of the patient's experience of illness." At both time points, doctors dominated the exchange and were patient-centered. DISCUSSION: Mindfulness has a direct and positive impact on clinicians' well-being. When clinicians' experienced less depersonalization, their patients reported being better understood.

Synthesis of spiro[isoindole-1,5'-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction.

A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N-benzylnitrone with isoindolin-3-methylene-1-ones. The regio- and stereoselectivity of the process have been rationalized by computational methods. The obtained compounds show cytotoxic properties and antiproliferative activity in the range of 9-22 µM. Biological tests suggest that the antitumor activity could be linked to the inhibition of the protein-protein p53-MDM2 interaction. Docking measurements support the biological data.

Grasping the sound: Auditory pitch influences size processing in motor planning.

Growing evidence shows that individuals consistently match auditory pitch with visual size. For instance, high-pitched sounds are perceptually associated with smaller visual stimuli, whereas low-pitched sounds with larger ones. The present study explores whether this crossmodal correspondence, reported so far for perceptual processing, also modulates motor planning. To address this issue, we carried out a series of kinematic experiments to verify whether actions implying size processing are affected by auditory pitch. Experiment 1 showed that grasping movements toward small/large objects were initiated faster in response to high/low pitches, respectively, thus extending previous findings in the literature to more complex motor behavior. Importantly, auditory pitch influenced the relative scaling of the hand preshaping, with high pitches associated with smaller grip aperture compared with low pitches. Notably, no effect of auditory pitch was found in case of pointing movements (no grasp implied, Experiment 2), as well as when auditory pitch was irrelevant to the programming of the grip aperture, that is, in case of grasping an object of uniform size (Experiment 3). Finally, auditory pitch influenced also symbolic manual gestures expressing "small" and "large" concepts (Experiment 4). In sum, our results are novel in revealing the impact of auditory pitch on motor planning when size processing is required, and shed light on the role of auditory information in driving actions.

Halogen and Hydrogen Bonding Benzothiophene Diol Derivatives: A Study Using ab†initio Calculations and X-Ray Crystal Structure Measurements.

The aim of this study is to describe and compare the supramolecular interactions, in the solid state, of chloro-, bromo-, and iodobenzothiophene diols. The compounds were obtained through organo-catalyzed reactions starting from 3-substituted halobenzothiophene carbaldehydes. Energies of the noncovalent interactions were obtained by density functional theory calculations. Bond distances and angles were found to be in accordance with those determined by X-ray structure analysis. anti-Bromobenzothiophene derivatives showed strong halogen⋅⋅⋅π interactions between bromine and the heterocyclic phenyl ring, corresponding to an energy of 7.5 kcal mol(-1). syn-Bromo and syn-iodo derivatives appeared to be isostructural, showing X⋅⋅⋅O (carbonyl) interactions, π stacking, and formation of extended hydrogen bonding networks. In contrast, the chloro derivatives displayed no halogen bonding interactions.

Crystal structure of N,N'-bis-(4-methyl-phen-yl)di-thio-oxamide.

Two half mol-ecules of the title compound, C16H16N2S2, are present in the asymmetric unit and both mol-ecules are completed by crystallographic inversion centers at the mid-points of the central C-C bonds: the lengths of these bonds [1.538 (5) and 1.533 (5) Å] indicate negligible electronic delocalization. The trans-di-thio-oxamide fragment in each mol-ecule is characterized by a pair of intra-molecular N-H⋯S hydrogen bonds. In the crystal, mol-ecules are linked by weak C-H..π inter-actions, generating a three-dimensional network.

Crystallographic study and biological evaluation of 1,4-dimethyl-N-alkylcarbazoles.

The 9-(bromoalkyl)-1,4-dimethyl-9H-carbazole (2a-d) derivatives, characterized by the presence of five or seven methylenic spacer groups bonded to the carbazole nitrogen, have been synthesized from the corresponding 1,4- dimethyl-9H-carbazole and appropriate dibromoalkane following a general synthetic method. All the prepared species have been fully characterized by means of IR, and (1)H and (13)C NMR spectroscopy, GC-MS and Elemental analysis. Good crystals of the 2c have been obtained and the crystal structure has been solved by means of X-ray diffractometry. In order to study the cytotoxic effect of 2a, 2b, 2c, 2d carbazole derivatives on A2780 ovarian cancer cells, we performed MTT assay after exposure of this cell population to those compounds in a concentration range from 1 to 10µM. Finally, we want to verify whether the cytotoxic effect of the 2c carbazole is mediated by apoptotic mechanisms, by performing chromatin condensation assay on the A2780 cell cultures upon the carbazole treatment at concentration of 10 µM for 72h. All together our data demonstrate that carbazole derivatives exert inhibitory effects on ovarian cancer cell growth, highlighting a stronger and a dose-dependent anti proliferative activity displayed by 2c carbazole, designating this compound, as a better candidate in the treatment of human ovarian cancer.

{2,6-Bis[(pyridin-2-yl)sulfanylmeth-yl]pyridine-κ(2) N,N'}(η(3)-prop-2-en-yl)palladium(II) hexa-fluoro-phosphate.

The title compound, [Pd(C3H5)(C17H15N3S2)]PF6, is built up by a [(η(3)-all-yl)Pd](2+) fragment coordinated by a 2,6-bis-[(pyridin-2-yl)sulfanylmeth-yl]pyridine ligand coordinated through the N atoms. One of the S atoms is at a close distance to the metal centeratom [3.2930 (8) Å]. The Pd(II) atom is tetra-coordinated in a strongly distorted square-planar environment mainly determined by the η(3)-allyl anion in which the central C atom is disordered over two equally occupied positions. The crystal packing is very compact and is characterized by a three-dimensional network of C-H⋯F interactions between the F atoms of each anion and several H atoms of the surrounding cationic complexes.

Synthesis, characterization, crystal structure, and biological studies of two new Cd (II) complexes with 4'-(4-chlorophenyl)-2,2' :6',2"-terpyridine (Clphtpy).

Two new Cd(II) complexes, with the ligand 4'-(4-chlorophenyl)-2,2':6',2"-terpyridine (Clphtpy) formulated as: [Cd(Clphtpy)(NO3)2H2O] (1), and [Cd(Clphtpy)(N3)2]2 (2), have been synthesized and characterized by CHN elemental analysis as well as FT-IR, 1H NMR, absorption and emission spectroscopy, thermal analysis and analyzed structurally by X-ray single-crystal diffraction. The single crystal X-ray analysis showed that the coordination number in complex 1 and 2 were seven and six with N3O4 and N6 coordination sphere, respectively. The antibacterial activities of the synthesized complexes were tested against four gram-positive and four gram-negative bacteria. A biological study of the complexes indicated that the complex 1 exhibited very good activity against most of the tested bacteria and its activity was better than gentamicin as a standard antibiotic.

Tetra-kis(µ-4-chloro-benzoato-κ(2) O:O')bis-[(ethanol-κO)copper(II)](Cu-Cu).

In the centrosymmetric dinuclear title Cu(II) complex, [Cu2(C7H4ClO2)(C2H5OH)2], the Cu-Cu distance is 2.5905 (4) Å. The two metal atoms are bridged by four 4-chloro-benzoate ligands and each has an ethanol mol-ecule in the axial position of the overall octahedral coordination environment. The crystal packing features O-H⋯O hydrogen bonds.

Dianilinium bis-(pyridine-2,6-dicarboxyl-ato-κ(3)O(2),N,O(6))cuprate(II) hexa-hydrate.

The asymmetric unit of the title complex, (C(6)H(8)N)(2)[Cu(C(7)H(3)NO(4))(2)]·6H(2)O, contains half a copper(II)-dipicolinate complex located on a twofold rotation axis, one protonated aniline mol-ecule and three solvent water mol-ecules. The Cu(II) atom is coordinated by four O atoms and two N atoms from two dipicolinate ligands in a distorted octa-hedral environment. In the crystal, the components are linked into a three-dimensional framework by inter-molecular O-H⋯O and N-H⋯O inter-actions.

5-Amino-3-methyl-1,2-oxazole-4-carbonitrile.

In the title compound, C(5)H(5)N(3)O, the isoxazole ring is essentially planar, with a maximum deviation of 0.007 (1) Šfrom the least-squares plane. The N atom of the amine group exhibits sp(2) character (sum of bond angles around this atom = 358°). In the crystal, mol-ecules are aggregated by two kinds of N-H⋯N hydrogen bonds into fused R(2) (2)(12) and R(6) (6)(26) rings, forming a slightly puckered two-dimensional array lying parallel to (101).

Gaze direction and request gesture in social interactions.

One of the most important faculties of humans is to understand the behaviour of other conspecifics. The present study aimed at determining whether, in a social context, request gesture and gaze direction of an individual are enough to infer his/her intention to communicate, by searching for their effects on the kinematics of another individual's arm action. In four experiments participants reached, grasped and lifted a bottle filled of orange juice in presence of an empty glass. In experiment 1, the further presence of a conspecific not producing any request with a hand and gaze did not modify the kinematics of the sequence. Conversely, experiments 2 and 3 showed that the presence of a conspecific producing only a request of pouring by holding the glass with his/her right hand, or only a request of comunicating with the conspecific, by using his/her gaze, affected lifting and grasping of the sequence, respectively. Experiment 4 showed that hand gesture and eye contact simultaneously produced affected the entire sequence. The results suggest that the presence of both request gesture and direct gaze produced by an individual changes the control of a motor sequence executed by another individual. We propose that a social request activates a social affordance that interferes with the control of whatever sequence and that the gaze of the potential receiver who held the glass with her hand modulates the effectiveness of the manual gesture. This paradigm if applied to individuals affected by autism disorder can give new insight on the nature of their impairment in social interaction and communication.

[(Pyridine-2,6-dicarboxyl-ato)copper(II)]-µ-(pyridine-2,6-dicarboxyl-ato)-[bis-(ethyl-enediamine)-copper(II)]-µ-(pyridine-2,6-dicarboxyl-ato)-[(pyridine-2,6-dicarboxyl-ato)copper(II)] ethyl-enediamine monosolvate tetra-hydrate.

The title compound, [Cu(3)(C(7)H(3)NO(4))(4)(C(2)H(8)N(2))(2)]·C(2)H(8)N(2)·4H(2)O, was obtained by the reaction of copper(II) acetate dihydrate with pyridine-2,6-dicarb-oxy-lic acid (H(2)dipic) and ethyl-enediamine (en) in an aqueous solution. All of the Cu(II) atoms in the trinuclear centrosymmetric title complex are six-coordinated in a distorted octa-hedral geometry with N(2)O(4) and N(4)O(2) environments for the outer and central Cu(II) atoms, respectively. Various inter-actions, including numerous O-H⋯O and C-H⋯O hydrogen bonds and C-O⋯π stacking of the pyridine and carboxyl-ate groups [O⋯centroid distances = 3.669 (2) and 3.668 (2) Å] are observed in the crystal structure.