Synthesis and Structural Characterization of p-Carboranylamidine Derivatives.

In this contribution, the first amidinate and amidine derivatives of p-carborane are described. Double lithiation of p-carborane (1) with n-butyllithium followed by treatment with 1,3-diorganocarbodiimides, R-N=C=N-R (R = iPr, Cy (= cyclohexyl)), in DME or THF afforded the new p-carboranylamidinate salts p-C2H10B10[C(NiPr)2Li(DME)]2 (2) and p-C2H10B10[C(NCy)2Li(THF)2]2 (3). Subsequent treatment of 2 and 3 with 2 equiv. of chlorotrimethylsilane (Me3SiCl) provided the silylated neutral bis(amidine) derivatives p-C2H10B10[C{iPrN(SiMe3)}(=NiPr)]2 (4) and p-C2H10B10[C{CyN(SiMe3)}(=NCy)]2 (5). The new compounds 3 and 4 have been structurally characterized by single-crystal X-ray diffraction. The lithium carboranylamidinate 3 comprises a rare trigonal planar coordination geometry around the lithium ions.

Inherited cases of CNOT3-associated intellectual developmental disorder with speech delay, autism, and dysmorphic facies.

De novo pathogenic variants in CNOT3 have recently been reported in a developmental delay disorder (intellectual developmental disorder with speech delay, autism, and dysmorphic facies [IDDSADF, OMIM: #618672]). The patients present with a variable degree of developmental delay and behavioral problems. To date, all reported disease-causing variants occurred de novo and no parent-child transmission was observed. We report for the first time autosomal dominant transmissions of the CNOT3-associated developmental disorder in two unrelated families. The clinical characteristics in our patients match the IDDSADF features reported so far and suggest substantial variability of the phenotype within the same family.

An unsymmetrical dinuclear scandium complex comprising salophen ligands [H2salophen = N,N'-bis-(salicyl-idene)-1,2-phenyl-enedi-amine].

Treatment of scandium nitrate tetra-hydrate with the tetra-dentate ligand H2salophen [N,N'-bis-(salicyl-idene)-1,2-phenyl-enedi-amine] afforded the yellow dinuclear complex Sc(NO3)2(µ-salophen)Sc(salophen)(EtOH) or [Sc2(C20H14N2O2)2(NO3)2(C2H6O)] (systematic name: (ethanol-κO)bis-(nitrato-κ2 O,O'){µ-2,2'-[1,2-phenyl-enebis(nitrilo-methanylyl-idene)]diphenolato-κ4 N,N',O,O':κ2 O,O'}{2,2'-[1,2-phenyl-enebis(nitrilo-methanylyl-idene)]diphenolato-κ4 O,N,N',O'}discandium). In this compound, one salophen ligand displays a bridging coordination via the two oxygen atoms, while the other salophen ligand is attached to only one Sc center. This arrangement is stabilized by a hydrogen-bonded EtOH co-ligand, and by π-π stacking inter-actions between the two salophen ligands.

Formation and structural characterization of a potassium amidino-guanidinate.

The first potassium amidino-guanidinate complex, catena-poly[[bis-(µ-1-amidinato-N,N',N'',N'''-tetra-iso-propyl-guanidinato-κ5 N 1:N 1,N 2:N 2,N 4)dipotassium]-µ-1,2-di-meth-oxy-ethane-κ2 O:O'], [K2(C14H32N4)2(C4H10O2)] n or [{ i PrN= CHN( i Pr)N(N i Pr)2K}2(µ-DME)] n where DME is 1,2-di-meth-oxy-ethane, has been synthesized and structurally characterized. The title compound was isolated in 76% yield from a reaction of N,N'-diiso-propyl-carbodi-imide with potassium hydride in DME. The single-crystal X-ray structure determination of the title compound revealed a polymeric chain structure comprising cage-like dimeric units, with the amidino-guanidinate ligand displaying a mixed σ-/π-coordination mode.

Synthesis and structural characterization of four di-chlorido-bis-(cyclo-propyl-alkynyl-amidine)-metal complexes.

Deliberate hydrolysis of lithium cyclo-propyl-alkynylamidinates, Li[c-C3H5-C≡C(NR')2] [R' = i Pr, Cy = cyclo-hex-yl)], afforded the hitherto unknown neutral cyclo-propyl-alkynyl-amidine derivatives c-C3H5-C≡C-C(NR')(NHR') [R' = i Pr (1), Cy (2)]. Subsequent reactions of 1 or 2 with metal(II) chlorides, MCl2 (M = Mn, Fe, Co), provided the title complexes di-chlorido-bis-(3-cyclo-propyl-N,N'-diisopropyl-prop-2-ynamidine)-manganese(II), [MnCl2(C12H20N2)2], (3), di-chlorido-bis-(3-cyclo-propyl-N,N'-diisopropyl-prop-2-ynamidine)-iron(II), [FeCl2(C12H20N2)2], (4), di-chlorido-bis-(N,N'-di-cyclo-hexyl-3-cyclo-propyl-prop-2-ynamidine)-iron(II), [FeCl2(C18H28N2)2], (5), and di-chlorido-bis-(N,N'-di-cyclo-hexyl-3-cyclo-propyl-prop-2-ynamidine)-cobalt(II), [CoCl2(C18H28N2)2], (6), or more generally MCl2[c-C3H5-C≡C-C(NR')(NHR')]2 [R' = i Pr, M = Mn (3), Fe (4); R' = Cy, M = Fe (5), Co (6)] in moderate yields (30-39%). Besides their spectroscopic data (IR and MS) and elemental analyses, all complexes 3-6 were structurally characterized. The two isopropyl-substituted complexes 3 and 4 are isotypic, and so are the cyclo-hexyl-substituted complexes 5 and 6. In all cases, the central metal atom is coordinated by two Cl atoms and two N atoms in a distorted-tetra-hedral fashion, and the structure is supported by intra-molecular N-H⋯Cl hydrogen bonds.

The "Wanderlust" of Me3Si groups in rare-earth triple-decker complexes: a combined experimental and computational study.

The migration of Me3Si groups ("Wanderlust") in rare-earth triple-decker sandwich complexes of the type Ln2(COT'')3 (COT'' = bis(trimethylsilyl)cyclooctatetraenyl) has been elucidated by a combined experimental and computational study. For the first time, two isomers of a Ln2(COT'')3 triple-decker have been isolated and characterized in the case of Y2(COT'')3.

Three new types of transition metal carboranylamidinate complexes.

Three new types of transition metal carboranylamidinate complexes are reported. The tetranuclear Mn(ii) complex Mn4Cl6[(o-C2B10H10)C(NiPr)(NHiPr)]2(THF)4·THF (2) was prepared by treatment of anhydrous MnCl2 with Li[(o-C2B10H10)C(NiPr)(NHiPr)] ([double bond, length as m-dash]Li[HLiPr]) in THF, while the analogous reaction with FeCl2 afforded ionic [Li(DME)3][FeCl2{(o-C2B10H10)C(NiPr)(NHiPr)}] (3). The dinuclear Mo(ii) complex Mo2[(o-C2B10H10)C(NiPr)(NHiPr)]2(OAc)2·2THF (4), obtained from Mo2(OAc)4 and 2 equiv. of Li[HLiPr], represents the first example of a M-M multiple bond stabilized by carboranylamidinate ligands. All title compounds were structurally characterized by single-crystal X-ray diffraction. The M-M bonding in compound 4 has been further elucidated through Complete Active Space Self Consistent Field (CASSCF) calculations.

Synthesis and crystal structures of two new tin bis-(carboranylamidinate) complexes.

Reaction of 2 equiv. of the lithium carboranylamidinate Li[o-(C2H10B10)C(NCy)(NHCy)] with SnCl2 in THF afforded the stannylene compound bis(N,N'-dicyclohexylamidinatocarboranate)tin(II), SnII[o-(C2H10B10)C(NCy)(NHCy)]2 (1). A similar reaction of SnCl4 with 2 equiv. of Li[o-(C2H10B10)C(N i Pr)(NH i Pr)] unexpectedly afforded the known solvated penta-chlorido-stannate(IV) salt [Li(THF)4][SnCl5(THF)] as the main reaction product. Small amounts of the new chlorido-tin(IV) bis-(carboranylamidinate) bis(N,N'-diiso-propylamidinatocarboranate)chloridotin(IV), SnIVCl[o-(C2H10B10)C(N i Pr)(NH i Pr)][o-(C2H10B10)C(N i Pr)2] (2), were isolated as a by-product. Single-crystal X-ray structure analysis revealed a κC,κN-chelating coordination of the carboranylamidinate ligands in both 1 and 2. The Sn atom in 1 adopts a pseudo-trigonal-bipyramidal coordination under participation of a stereoactive lone pair. In 2, a trigonal-bipyramidal coordination of Sn is completed by a chlorido ligand.

High-yield synthesis of a unique Mn(iii) siloxide complex through KMnO4 oxidation of a Mn(ii) precursor.

A unique trivalent manganese siloxide complex, blue-violet MnIIILi2Cl[(Ph2SiO)2O]2(THF)4·2THF (3) has been prepared by a straightforward two-step synthetic protocol. Lithiation of (Ph2SiOH)2O (1) followed by reaction with MnCl2(THF)2 gave the structurally remarkable Mn(ii) precursor MnIILi4Cl2[(Ph2SiO)2O]2(THF)5·2THF (2). Surprisingly, the final oxidation step could be achieved using KMnO4 in THF to provide the Mn(iii) species 3 in high yield (91%). Both title compounds were structurally characterized by single-crystal X-ray diffraction.

Scandium-Mediated Formation of a Bis(tetrahydropentalene).

The reactivity of Li[Sc(COT'')2 ] (1; COT''=1,4-bis(trimethylsilyl)cyclooctatetraenyl) towards CoCl2 is considerably different from that of related lanthanide triple-decker sandwich complexes. In addition to the expected triple-decker complex Sc2 (COT'')3 (2), the complex Sc2 {µ-BTHP}(COT'')2 (3) is formed, which comprises the novel BTHP2- ligand (BTHP2- =bis(3,5-bis(trimethylsilyl)-1,3a,6,6a-tetrahydropentalene-1-yl)diide or bis(2,7-bis(trimethylsilyl)bicyclo[3.3.0]octa-2,7-dien-4-yl)diide, C16 H10 (SiMe3 )42- ). The formation of 3 is likely facilitated by the fact that scandium prefers η8 ,η3  coordination rather than highly symmetric η8 ,η8  coordination, and the η3 -coordinated COT'' ligand in 1 is activated owing to a loss of aromaticity. Acid hydrolysis of 3 leads to air-stable H2 BTHP (4).

Five different types of η(8)-cyclooctatetraenyl-lanthanide half-sandwich complexes from one ligand set, including a "giant neodymium wheel".

The lithium-cyclopropylethynylamidinates Li[c-C3H5-C[triple bond, length as m-dash]C-C(NR)2] (1a: R = (i)Pr, 1b: R = cyclohexyl (Cy)) have been used as precursors for the preparation of five new series of half-sandwich complexes. These complexes contain the large flat cyclooctatetraenyl ligand (C8H8(2-), commonly abbreviated as COT), and were isolated as solvated, unsolvated and inverse sandwich complexes. Treatment of the halide precursors [(COT)Pr(µ-Cl)(THF)2]2 with 1b and [(COT)Nd(µ-Cl)(THF)2]2 with 1a and 1b in THF in a 1 : 2 molar ratio, respectively, afforded (COT)Ln[µ-c-C3H5-C[triple bond, length as m-dash]C-C(NR)2]2Li(L) (2: Ln = Pr, R = Cy, L = Et2O; 3: Ln = Nd, R = (i)Pr, L = THF; 4: Ln = Nd, R = Cy, L = THF). Treatment of the dimeric cerium(iii) bis(cyclopropylethynylamidinate) complexes [{c-C3H5-C[triple bond, length as m-dash]C-C(NR)2}2Ce(µ-Cl)(THF)]2 (5: R = (i)Pr; 6: R = Cy) in situ with K2C8H8 in a 1 : 1 molar ratio in THF at room temperature afforded the inverse-sandwich complexes (µ-η(8):η(8)-COT)[Ce{c-C3H5-C[triple bond, length as m-dash]C-C(NR)2}2]2 (7: R = (i)Pr; 8: R = Cy). This reaction represents a new method for encapsulation of a planar (C8H8)(2-) ring in lanthanide complexes containing amidinate ligands in the outer decks. Novel unsolvated dinuclear lanthanide half-sandwich complexes were prepared by using the precursors 1a, 1b and COT(2-). Unlike the complexes 2-4, the reaction of [(COT)Pr(µ-Cl)(THF)2]2 with 1a afforded the unsolvated centrosymmetric complex [(COT)Pr(µ-c-C3H5-C[triple bond, length as m-dash]C-C(N(i)Pr)2)]2 (9). These dimeric structures could be also accessed by reaction of LnCl3 (Ln = Ce or Nd) with 1a or 1b and K2COT in a 1 : 1 : 1 molar ratio as a one-pot reaction to give novel [(COT)Ln(µ-c-C3H5-C[triple bond, length as m-dash]C-C(NR)2)]2 complexes (10: Ln = Ce, R = (i)Pr; 11: Ln = Ce, R = Cy; 12: Ln = Nd, R = (i)Pr). Similar treatment of HoCl3 with 1a or 1b and K2COT as three-component reactions in a 1 : 1 : 1 molar ratio afforded the solvated half-sandwich complexes (COT)Ho(c-C3H5-C[triple bond, length as m-dash]C-C(NR)2)(THF) (13: R = (i)Pr; 14: R = Cy). A unique multidecker sandwich complex [(µ-η(8):η(8)-COT){Nd(c-C3H5-C[triple bond, length as m-dash]C-C(NCy)2)(µ-Cl)}2]4 (15) was prepared by reaction of anhydrous NdCl3 with K2COT and 1b in a one-pot reaction. The solid state structure of 15 revealed the presence of an unprecedented macrocyclic sandwich compound ("giant neodymium wheel") consisting of four COT rings sandwiched between eight Nd(3+) ions, and each Nd(3+) ion is bonded to one amidinate ligand and bridged by two chlorine atoms with the neighbouring Nd(3+) ion.

Novel inorganic heterocycles from dimetalated carboranylamidinates.

Mono- and dianionic carboranylamidinates are readily available in one-pot reactions directly from o-carborane (1). In situ-monolithiation of 1 followed by treatment with N,N'-diisopropylcarbodiimide, (i)PrN=C=N(i)Pr, or N,N'-dicyclohexylcarbodiimide, CyN=C=NCy, provided the lithium carboranylamidinates (o-C2B10H10C(NH(i)Pr)(=N(i)Pr)-κ(2)C,N)Li(DME) (2a) and (o-C2B10H10C(NH(i)Cy)(=N(i)Cy)-κ(2)C,N)Li(THF)2 (2b). Controlled hydrolysis of 2a,b afforded the free carboranylamidines o-C2B10H11C(NH(i)R)(=N(i)R) (3a: R = (i)Pr, 3b: R = Cy). The first dimetalated carboranylamidinates, o-C2B10H10C(N(i)Pr)(=N(i)Pr)Li2(DME)2 (4a) (DME = 1,2-dimethoxyethane) and o-C2B10H10C(N(i)Pr)(=N(i)Pr)Li2(THF)4 (4b), were prepared in high yield (83% yield) directly from 1 using a simple one-pot synthetic protocol. Treatment of 4b with 2 equiv. of Me3SiCl afforded the disilylated derivative o-C2B10H10-κ(2)C,N-[C(N(i)PrSiMe3)(=N(i)Pr)]SiMe3 (5). Dianionic 4b also served as an excellent precursor for novel inorganic heterocycles incorporating the closo-1,2-C2B10H10 cage, including the unsymmetrical distannene [o-C2B10H10C(N(i)Pr)(=N(i)Pr)-κ(2)C,N]Sn=Sn[((i)PrN)2C(n)Bu]2 (6) and the azaphosphole derivative [o-C2B10H10C(N(i)Pr)(=N(i)Pr)-κ(2)C,N]PPh (7). Surprisingly, it was found that the synthesis of new inorganic ring systems from dianionic carboranylamidinates can also be achieved by employing only 1 equiv. of n-butyllithium in the generation of the anionic carboranylamidinate intermediates. Using this straightforward one-pot synthetic protocol, the Group 14 metallacycles [o-C2B10H10C(NCy)(=NCy)-κ(2)C,N]SiR2 (R = Cl (8), Me (9), Ph (10)) and [o-C2B10H10C(NCy)([=NCy)-κ(2)C,N]GeCl2 (11) have become accessible. The same synthetic strategy could be successfully adapted to prepare the corresponding Group 4 metallocene derivatives Cp2Ti[o-C2B10H10C(NCy)(=NCy)-κ(2)C,N] (12) and Cp2Zr[o-C2B10H10C(NCy)(=NCy)-κ(2)C,N] (13). The molecular structures of 2b, 3b, 4b, 5, 6, 7, 10, 12, and 13 were confirmed by single-crystal X-ray diffraction.

Facioaudiosymphalangism syndrome and growth acceleration associated with a heterozygous NOG mutation.

We report on a father and son with facioaudiosymphalangism syndrome, an alternative designation for multiple synostoses syndrome, type I. This syndrome includes synostosis, brachydactyly, craniofacial dysmorphic features, stapes fixation, hyperopia, and growth retardation. In contrast to the typical presentation, the height of the 10-year-old son was above the 97th centile from the age of 3.5 years and he had markers of an activated bone metabolism. The father and son had a novel heterozygous missense mutation c.696C > G, p.Cys232Trp, in the NOG gene. While not yet described in human NOG-related disorders, there is experimental evidence that suppression of noggin might accelerate osteogenesis, which could explain the phenotype in the family reported here.

Pure distal trisomy 2q: a rare chromosomal abnormality with recognizable phenotype.

We present clinical and molecular cytogenetic results of two unrelated patients with isolated distal trisomy of 2q33-qter and 2q35-q37.3 and a remarkable similar facial appearance. Common craniofacial features included a high hairline, broad nasal bridge, prominent nasal tip, thin upper lip vermillion, and large ears. Contrary to patients with duplications proximal to 2q33, the children with pure trisomy distal to 2q35 have normal or increased body measurements and show no major malformations. Moderate psychomotor delay was a constant finding.

Cardiac medications are not associated with clinically important preoperative electrolyte disturbances in children presenting for cardiac surgery.

BACKGROUND: Preoperative laboratory examination of patients undergoing elective surgical procedures has been routinely performed for decades. Although there is a large body of literature concerning the appropriate preoperative assessment of adult patients, corresponding literature for the pediatric population is not as well defined. Children and young adults with cardiac disease are a particularly vulnerable subset of patients who often undergo an extensive battery of preoperative laboratory testing. We examined the serum chemistry profiles for children with cardiac disease presenting for outpatient surgery. The investigation aims to define the effectiveness of preoperative electrolyte determination in this population of children and young adults. METHODS: A retrospective chart review of all children presenting as outpatients to a tertiary care, freestanding children's hospital for elective cardiac surgery between January 1, 2000 and January 31, 2003 was performed. All patient charts in which the admission date matched the cardiac surgical date were examined. Patients were excluded if the preoperative laboratory evaluation was performed outside of our facility, preoperative laboratory investigation was not performed, or the patient was transported by medical transport to our hospital. Patients were grouped according to three methods: the number of cardiac medications (none to four), and cardiac medications, noncardiac medications, and no medications. The presence of electrolyte abnormalities was also examined in the context of cardiac medications with various pharmacologic effects. The primary outcome measure was the incidence of abnormal laboratory values for children taking various cardiac medications. RESULTS: Of the 933 initial entries found, 774 met the investigational criteria and were included in the analysis. Although statistically significant differences in preoperative electrolytes were associated with the use of cardiac and noncardiac medication, there was no clinical value to this correlation. The data demonstrate a very low incidence of hypokalemia and hypomagnesemia in the entire study population. CONCLUSION: Preoperative electrolyte disturbances in children and young adults presenting for cardiac surgery are uncommon. The concern of hypokalemia or hypomagnesemia important in the adult population taking cardiac medications was not identified in the pediatric population. These data do not support the need for routine preoperative electrolyte evaluation in children taking cardiac medications.

Comparison of immediate and delayed automatic antitachycardia pacing for the termination of atrial tachyarrhythmias.

AIMS: Automatic atrial antitachycardia pacing (ATP) can terminate atrial tachyarrhythmias (ATs) in patients with an implanted device. We investigated if the programmable delay between AT onset and ATP influences therapy efficacy. METHODS: Patients with intermittent ATs and an implanted DDDRP pacemaker were randomized to receive ATP either immediately or 30min after AT detection. After four months stored data were interrogated, AT-related symptoms were assessed, and patients crossed over to the alternative treatment arm for another four months. Stored atrial electrograms were analyzed for degree of AT organization and ATP success. RESULTS: In 22 patients (64% male; 72+/-7 years), ATP success rates were higher during immediate than during delayed ATP (device classification: 59+/-7% vs. 22+/-5%, P<0.01; manual analysis: 36+/-6% vs. 12+/-5%, P<0.01). Higher efficacy of immediate ATP was associated with a larger proportion of organized (Type I) AT prior to therapy (71% vs. 44% during delayed ATP). No difference was found in total AT numbers and duration, AT burden or related symptoms. CONCLUSIONS: The programmable delay between arrhythmia onset and therapy delivery significantly influences the success-rate of ATP. However, a higher efficacy of immediate compared with delayed ATP does not translate into a reduction of AT burden or related symptoms.