Unexpected low thermal expansion coefficients of pentadiamond.

A new carbon allotrope, pentadiamond, was recently reported in the literature. Herein, we investigate its thermal expansion and thermoelastic properties by first principles. It is observed that the bulk modulus and hardness of pentadiamond are far less than those of diamond, but the thermal expansion of pentadiamond is lower than that of diamond in the range of 0 K to 2000 K, and even negative in the temperature range of 0-190 K. The negative thermal expansion at low temperature originates from the transverse vibrations of the edge-shared atoms in the coplanar double-pentagon. The low thermal expansion at high temperature is contributed by the strong bonds in pentadiamond. Benefiting from the low thermal expansion, the elastic constants of pentadiamond decrease very slowly with respect to temperature compared with those of diamond. The low sensitivity of thermodynamic and thermoelastic properties to temperature makes pentadiamond a promising material for high anti-thermal-shock and accurate electronic device applications.

Discovery of 1-(3,4-dichlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydroquinolin-4-amine, a dual serotonin and dopamine reuptake inhibitor.

The present work describes a series of novel tetrahydroquinoline amines that potently inhibit the in vitro reuptake of serotonin and dopamine (dual reuptake inhibitors). The compounds are structurally related to a series we disclosed previously, but are improved with respect to cytochrome P-450 enzyme (CYP) and potassium ion channel Kv11.1 (hERG) inhibition and synthetic accessibility. The detailed synthesis and in vitro activity and ADME profile of the compounds is described, which represent a previously undisclosed dual reuptake inhibitor chemotype.

Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor.

The current work discloses a novel cyclohexylarylamine chemotype with potent inhibition of the serotonin, norepinephrine, and dopamine transporters and potential for treatment of major depressive disorder. Optimized compounds 1 (SERT, NET, DAT, IC(50)=169, 85, 21 nM) and 42 (SERT, NET, DAT IC(50)=34, 295, 90 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 30 mpk po and were not general motor stimulants.

Discovery of N-methyl-1-(1-phenylcyclohexyl)ethanamine, a novel triple serotonin, norepinephrine and dopamine reuptake inhibitor.

Novel chiral cyclohexylaryl amines were developed with potent reuptake inhibition against the serotonin, norepinephrine and dopamine transporters and activity at 10 and 30 mpk PO in the mouse tail suspension test. Prototype compound 31 (SERT, NET, DAT IC(50) ≤ 1, 21, 28 nM) was highly brain penetrant, had minimal CYP and hERG inhibition, and represents a previously undisclosed architecture with potential for treatment of major depressive disorder.

Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors.

The present work describes a series of novel chiral amines that potently inhibit the in vitro reuptake of serotonin, norepinephrine and dopamine (triple reuptake inhibitors) and were active in vivo in a mouse model predictive of antidepressant like activity. The detailed synthesis and in vitro activity and ADME profile of compounds is described, which represent a previously undisclosed triple reuptake inhibitor chemotype.

mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I).

Novel compounds were prepared that united the pharmacologies of the mu-opioid tramadol with the 5-HT4 agonists metoclopramide and norcisapride. The synthesis, chiral separation and in vitro activity of the new compounds is described.

Effect of Trace Zn Addition on Interfacial Evolution in Sn-10Bi/Cu Solder Joints during Aging Condition.

Excessive growth of intermetallic compounds (IMCs) during service affects the reliability of solder joints, so how to suppress the growth of IMC thickness at the interface in solder joints becomes a widespread concern. In this work, the interfacial reaction between Sn-10Bi solder and Cu substrate after thermal aging was investigated. Moreover, to depress the IMC growth at the interface, trace amounts of Zn was added into the Sn-10Bi solder, and the interfacial reactions of Sn-10Bi-xZn solders (x = 0.2, 0.5) and Cu substrate after thermal aging were studied in this paper. Compounds such as Cu6(Sn, Zn)5 and Cu5Zn8 were formed at the interface after adding trace amounts of Zn. The addition of 0.2 and 0.5 wt% Zn significantly inhibited the thickness growth of IMCs and the formation of Cu3Sn IMC at the interface of Sn-10Bi-0.2Zn/Cu and Sn-10Bi-0.5Zn/Cu during thermal aging. Therefore, the addition of trace Zn had an obvious effect on the interfacial reaction of Sn-10Bi/Cu solder joint. Interestingly, the evolution of IMC thickness in Sn-10Bi-0.5Zn/Cu solder joints was completely different from that in Sn-10Bi or Sn-10Bi-0.2Zn solder joints, in which the spalling of IMCs occurred. In order to explore the mechanisms on the depressing effect from the addition of trace Zn, the activation energy Q in solder joints during aging was calculated.

Interfacial Reaction and Mechanical Properties of Sn-Bi Solder joints.

Sn-Bi solder with different Bi content can realize a low-to-medium-to-high soldering process. To obtain the effect of Bi content in Sn-Bi solder on the microstructure of solder, interfacial behaviors in solder joints with Cu and the joints strength, five Sn-Bi solders including Sn-5Bi and Sn-15Bi solid solution, Sn-30Bi and Sn-45Bi hypoeutectic and Sn-58Bi eutectic were selected in this work. The microstructure, interfacial reaction under soldering and subsequent aging and the shear properties of Sn-Bi solder joints were studied. Bi content in Sn-Bi solder had an obvious effect on the microstructure and the distribution of Bi phases. Solid solution Sn-Bi solder was composed of the ß-Sn phases embedded with fine Bi particles, while hypoeutectic Sn-Bi solder was composed of the primary ß-Sn phases and Sn-Bi eutectic structure from networked Sn and Bi phases, and eutectic Sn-Bi solder was mainly composed of a eutectic structure from short striped Sn and Bi phases. During soldering with Cu, the increase on Bi content in Sn-Bi solder slightly increased the interfacial Cu6Sn5 intermetallic compound (IMC)thickness, gradually flattened the IMC morphology, and promoted the accumulation of more Bi atoms to interfacial Cu6Sn5 IMC. During the subsequent aging, the growth rate of the IMC layer at the interface of Sn-Bi solder/Cu rapidly increased from solid solution Sn-Bi solder to hypoeutectic Sn-Bi solder, and then slightly decreased for Sn-58Bi solder joints. The accumulation of Bi atoms at the interface promoted the rapid growth of interfacial Cu6Sn5 IMC layer in hypoeutectic or eutectic Sn-Bi solder through blocking the formation of Cu6Sn5 in solder matrix and the transition from Cu6Sn5 to Cu3Sn. Ball shear tests on Sn-Bi as-soldered joints showed that the increase of Bi content in Sn-Bi deteriorated the shear strength of solder joints. The addition of Bi into Sn solder was also inclined to produce brittle morphology with interfacial fracture, which suggests that the addition of Bi increased the shear resistance strength of Sn-Bi solder.

Structure-Cytotoxicity Relationships of Analogues of N14-Desacetoxytubulysin H.

Herein we report structure-cytotoxicity relationships for analogues of N14-desacetoxytubulyisn H 1. A novel synthetic approach toward 1 enabled the discovery of compounds with a range of activity. Calculated basicity of the N-terminus of tubulysins was shown to be a good predictor of cytotoxicity. The impact of structural modifications at the C-terminus of 1 upon cytotoxicity is also described. These findings will facilitate the development of new tubulysin analogues for the treatment of cancer.

Structure- and reactivity-based development of covalent inhibitors of the activating and gatekeeper mutant forms of the epidermal growth factor receptor (EGFR).

A novel series of small-molecule inhibitors has been developed to target the double mutant form of the epidermal growth factor receptor (EGFR) tyrosine kinase, which is resistant to treatment with gefitinib and erlotinib. Our reported compounds also show selectivity over wild-type EGFR. Guided by molecular modeling, this series was evolved to target a cysteine residue in the ATP binding site via covalent bond formation and demonstrates high levels of activity in cellular models of the double mutant form of EGFR. In addition, these compounds show significant activity against the activating mutations, which gefitinib and erlotinib target and inhibition of which gives rise to their observed clinical efficacy. A glutathione (GSH)-based assay was used to measure thiol reactivity toward the electrophilic functionality of the inhibitor series, enabling both the identification of a suitable reactivity window for their potency and the development of a reactivity quantitative structure-property relationship (QSPR) to support design.

Synthesis and pharmacological characterization of bicyclic triple reuptake inhibitor 3-aryl octahydrocyclopenta[c]pyrrole analogues.

The present work expands the chemical space known to offer potent inhibition of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) and discloses novel bicyclic octahydrocyclopenta[c]pyrrole and octahydro-1H-isoindole scaffolds as potent triple reuptake inhibitors (TRIs) for the potential treatment of depression. Optimized compounds 22a (SERT, NET, DAT, IC(50) = 20, 109, 430 nM), 23a (SERT, NET, DAT, IC(50) = 29, 85, 168 nM), and 26a (SERT, NET, DAT, IC(50) = 53, 150, 140 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 10 and 30 mpk PO, and were not generally motor stimulants at doses ranging from 1 to 30 mpk PO. Moderate in vitro cytochrome P450 (CYP) and potassium ion channel Kv11.1 (hERG) inhibition were uncovered as potential liabilities for the chemical series.