Bu Group Research Articles

A comparison of the results of arterial embolization for bleeding and non-bleeding gastroduodenal ulcers

Although some authors have advocated the practice of arterial embolization for angiographically negative acute hemorrhage from gastroduodenal ulcers, this technique remains controversial. To compare the results of arterial embolization for bleeding (BU) and non-bleeding (NBU) gastroduodenal ulcers. Transcatheter embolization was performed in 57 patients (39 men, 18 women, mean age 69.8 years) who experienced acute bleeding from gastroduodenal ulcers. At the time of embolization active contrast extravasation was seen in 36 of 57 patients, while in the remaining 21 patients embolization was based on endoscopic findings. Patient demographics, clinical success, need for re-intervention secondary to re-bleeding, and 30-day complication and mortality rates were reviewed and compared between the two groups by using statistical analyses. In the BU group, the gastroduodenal artery (GDA) was embolized in 31 patients (86.1%), the left gastric artery (LGA) in three patients (8.3%), and the left gastroepiploic artery (LGEA) in two patients (5.6%). In the NBU group, the GDA was embolized in 18 patients (85.7%), and the LGA in three patients (14.3%). Clinical success (61.9 vs. 75.0%, P = 0.30), need for re-intervention (38.1 vs. 27.8%, P = 0.42), and 30-day complication (9.5 vs. 5.6%, P = 0.57), and mortality (28.6 vs. 25%, P = 0.77) rates were not statistically different between the two groups. Embolization in patients in NBU group did not have impact on clinical success (OR, 0.54; 95%CI, 0.17-1.72; P = 0.30). Arterial embolization in patients with angiographically NBU is as safe and effective as embolization in patients with BU.

Intravenous compared with oral busulfan as preparation for allogeneic hematopoietic progenitor cell transplantation for AML and MDS

BU and CY is a common conditioning regimen for allogeneic hematopoietic progenitor cell transplantation (HPCT). I.v. BU is increasingly used in place of the oral formulation for conditioning. We compared the outcomes of 135 consecutively treated AML and myelodysplastic syndrome patients who underwent allogeneic HPCT at our institution with BUCY2 using oral (n=93) or i.v. (n=42) BU, without dose adjustment. The i.v. BU patients had a lower incidence of any severity of oral mucositis (3 versus 55%, P=0.002) and severe mucositis (3 versus 24%, P=0.005). Other post transplant outcomes were comparable between the groups. In all 26 i.v. BU and 33 oral BU patients are alive; however, the median follow-up was significantly longer for the oral BU group. One- and two-year non-relapse mortality for the i.v. BU patients was 21% for both, and for the oral BU group was 23% and 29%, respectively. One- and two-year relapse mortality for the i.v. BU patients was 21% for both, and for the oral BU group was 24% and 29%, respectively. Substituting i.v. for oral BU reduces variability in drug exposure and potentially improves toxicity as suggested by our finding of significantly less oral mucositis and decreased severity with i.v. BU.

Synthesis, crystal structure and intermolecular magnetic interactions of a new N-TEMPO-3,5-di- tert-butylsalicylaldimine radical

A new N-TEMPO-3,5-di- tert-butylsalicylaldimine radical ( 1) has been synthesized and characterized by single crystal X-ray diffraction, elemental analysis, IR, UV–vis, and EPR spectroscopy and temperature dependent magnetic susceptibility. X-ray diffraction revealed that H-atoms of γ-CH in TEMPO and CH 3 in salicylaldimine moieties, are located in close contact with the neighboring N–O radical group in crystal 1. The temperature dependence of the magnetic susceptibility ( χ m) of 1 has been fitted by the Curie–Weiss law with θ = −0.3 K within 10–300 K, suggesting the presence of a weak intermolecular antiferromagnetic interaction between radical centers at T < 10 K. It has been demonstrated that radical 1 possesses crystal structure involving co-existence of antiferromagnetic and ferromagnetic interactions through C–H⋯O–N contacts of γ-CH and t Bu groups hydrogen atoms, in which the former path dominates over the latter.

Single center retrospective analysis of BU-based conditioning regimens in allogeneic transplantation

We performed a single institution retrospective analysis of 114 patients treated with BU-based pretransplant conditioning regimens. Oral BU was administered to 76 patients (total dose 16 mg/kg or 8 mg/kg) and i.v. BU to 38 others (total dose 12.8 mg/kg or 6.4 mg/kg). Either CY (n=74) or fludarabine (n=40) was given in combination with BU. Median age was 35 years in the oral BU group and 48.5 years with i.v. BU (P<0.001). OS and PFS rates at 3-years post HSCT were not different in patients who received either i.v. or oral BU (OS: 41.3 vs 44.0% (P=0.981); PFS: 52.7 vs 54.7% (P=0.526), respectively). The i.v. BU, however, was associated with a significantly shorter time to engraftment (13.5 days vs 16 days, respectively; P<0.001). There were no significant differences in survival or 100-day mortality for patients who received either CY or fludarabine, in combination with BU. After adjustment for confounders, multivariate analysis showed that age of transplant (P=0.002), donor type (sibling or unrelated; P=0.003), GVHD (P<0.05) and route of administration (P=0.023) were significant risk factors for OS. The i.v. BU used in an older age group yielded equivalent survival compared with oral BU used in a younger population.

An evaluation of monovalent osmium supported by the PNP ligand environment

Nitrogen is essential to reaction of (PNP)OsI (PNP is N(SiMe(2)CH(2)P(t)Bu(2))(2)) and Mg powder in THF, to give equimolar (PNP)OsH(N(2)) and hydrido carbene [((t)Bu(2)PCH(2)SiMe(2))N(SiMe(2)CH(2)P(t)Bu(CMe(2)CH)]OsH. This reaction is attributed to H(2) evolution from solid magnesium, rather than high energy H atom transfer between molecules, but relies also on the strong π-basicity of Os in favoring α-H migration from the metallated (t)Bu group on Os to form the second product, the hydrido carbene species. The path to two different products begins because the simple N(2) adduct of (PNP)OsI undergoes spontaneous heterolytic H-C splitting of the (t)Bu methyl group, to produce a secondary amine intermediate [((t)Bu(2)PCH(2)SiMe(2))N(H)(SiMe(2)CH(2)P(t)Bu(CMe(2)CH(2))]OsI(N(2)) which can then be dehydrohalogenated by Mg. The analogous reaction for (PNP)RuCl shows production of only (PNP)RuH(N(2)), with none of the hydride carbene dehydrogenation product. Comparative (Ru vs. Os) DFT calculations reveal the reaction steps where the Os analog is much more exothermic, accounting for certain reaction selectivities.

Intravenous Compared to Oral Busulfan with Cyclophophamide for Allogeneic Hematopoietic Progenitor Cell Transplant Conditioning for AML and MDS.

AbstractAbstract 3475Busulfan (Bu) is commonly used with cyclophosphamide (Cy) as a conditioning regimen for allogeneic hematopoietic progenitor cell transplantation (HPCT). Recently, intravenous (IV) Bu has often replaced oral Bu for conditioning. We have previously reported that substituting IV for oral Bu was associated with a lower rate of relapse, and superior relapse-free and overall survivals for relapsed or refractory non-Hodgkin lymphoma patients undergoing autologous HPCT (Dean et al. Br J Haematol 2010 Jan;148(2):226-34). We retrospectively compared the outcomes of 135 consecutively treated AML and MDS patients who underwent allogeneic HPCT at our institution from 5/2001 through 10/2009 with BuCy using oral (n = 93) or IV (n = 42) Bu, without dose adjustment. The analysis included matched related (n=97) and 8/8 HLA matched unrelated donors (n=38). Oral Bu was administered as 1 mg/kg every 6 hours for 16 doses while IV Bu was administered as 0.8 mg/kg every 6 hours for 16 doses (days –8 through -4) followed by Cy 60 mg/kg/day × 2 (days –3 and –2). The IV Bu patients were older (median age 49 vs. 47 yrs, respectively, p=0.037), more commonly had unrelated donors and peripheral blood stem cells for their HPCT cell source than those treated with oral Bu. There were no significant differences between the groups with regards to patient gender, race, CIBMTR comorbidity index score, number of prior chemotherapy regimens, pre-transplant disease status (each group had 45% of patients in CR1 or CR2), donor-recipient gender relationships or nucleated cell dose infused. The IV Bu group had a higher median CD34+ cell dose infused than those who received oral Bu (3.34 vs. 2.19 ×106/kg, respectively, p=0.028). The IV Bu patients experienced a significantly lower incidence of mucositis (3% vs. 55%, p<0.001) and less severe mucositis (median OMAS scores 0 vs.0.08, respectively, p<0.001). However, there were no significant differences between the IV and oral Bu groups in days until neutrophil and platelet count engraftment, length of transplant hospitalization, incidence of acute or chronic GVHD, sinusoidal obstruction syndrome, and 100 day mortality. At this time 26 (62%) of the IV Bu patients and 33 (36%) of the oral Bu patients are alive, however, the median follow-up was substantially longer for the oral Bu group (50 vs. 13 months, p<0.001). Disease relapse was the most common cause of death for both the IV and oral Bu patients accounting for approximately 50% of deaths in each group. The 1 and 2 year transplant-related mortality for the IV Bu patients was 21% for both, while that for the oral Bu group was 23% and 29%, respectively. The 1 and 2 year relapse mortality for the IV Bu patients was 21% for both, while that for the oral Bu group was 24% and 29%, respectively. Substituting IV for oral Bu reduces variability in drug exposure and potentially improves safety as suggested from our finding of significantly less severe oral mucositis in the IV Bu group. Further follow-up of the IV Bu group is required to adequately assess for a survival benefit. Whether pharmacokinetic-based Bu dosing can improve outcomes after allogeneic HPCT in this setting is worthy of further study. Disclosures:Sobecks:Otsuka Pharm.: Research Funding.

Pharmocokinetic (PK)-Directed High Dose Intravenous Busulfan, Cyclophosphamide and Etoposide Produces Predictable Drug Exposure and Durable Long Term Survival In Lymphoma Patients Undergoing Autologous Stem Cell Transplantation

AbstractAbstract 1359 Background:Improved survival has been observed after replacing oral with intravenous (iv) busulfan in autologous stem cell transplantation (ASCT) for lymphoma conditioned with busulfan (Bu), cyclophosphamide (Cy) and etoposide (VP-16; Dean et al., Br J Hematol. 2010), but it is unknown whether PK-directed iv Bu dosing is associated with additional improvements in safety or efficacy. To address this issue we performed an IRB-approved retrospective cohort study to compare the efficacy of PK-directed oral and iv Bu in lymphoma patients undergoing ASCT from 2000–2010 at Emory University. Methods:Patients included for analysis received oral Bu (1.0mg/kg every 6 hours × 16, n=97), or iv Bu (0.9mg/kg every 6 hours × 16, n=199) followed by Cy (60mg/kg qd × 2), etoposide (10 mg/kg qd x3) and infusion of previous collected autologous stem cells. Baseline demographic, lymphoma subtype, disease status, body weight (kg), body surface area (BSA), body mass index (BMI; kg/m2), stem cell dose, and other clinical and ASCT parameters were compared for oral and iv groups. Bu area under the curve (AUC), maximum bilirubin, and overall survival (OS) were compared for oral and iv groups using Chi-squared statistics and Cox regression models. Results:Diagnosis was comparable across two treatment groups except the oral treatment group had slightly higher number of NHL (58%) than iv group (43%, p=0.04). The median age and percentage of males were 43 (range 19–66) and 45 (17-69), 67% and 62.3% for oral and iv groups, respectively. Patients who received oral and iv Bu did not differ by race, mean weight, BMI, stem cell dose and disease status. BSA was greater in the iv busulfan group (p=0.03). Pharmacokinetic-directed dosing was performed in both treatment groups with a total target AUC of 20,000μMol-min. Following the initial Bu dose, the Bu half-life (mean ± std., oral: 225.8 ± 104.4, iv: 189.4 ± 47.5; p=0.0026) and total targeted AUC (oral: 20,534 ± 2,969, iv: 19,695 ± 1,434; p=0.01) were significantly different between two treatment groups. 44% of patients in oral group (n=94) and 88% of patients in the iv group (n=178) achieved targeted AUC between 18,000-22,000μMol-min. PK-directed Bu dosing generated a narrower AUC range in the iv treatment groups compared with that in the oral groups (Figure 1). Regimen-related toxicities, including VOD, were similar between patients in the oral and iv groups, with 100-day mortality of 3% and 4%, respectively (p=NS). With a mean follow-up of 1,521 and 789 days for oral and iv Bu groups, 58% and 72% patients were alive in each group respectively (Figure 2). In multivariate Cox regression models, age (HR=1.03, CL 1.01–1.05, p=0.001) significantly influenced survival, but route of Bu administration did not. Oral and iv PK-directed Bu had 2-year OS of 77% and 92% in this cohort. Conclusion:PK-directed iv Bu improves the consistency of delivering target AUC over oral PK-directed Bu with similar survival outcomes for lymphoma patients undergoing ASCT. The narrow CI for final AUC among patients receiving PK-directed iv Bu may safely permit dose-escalation of busulfan administered as part of high-dose conditioning to improve transplant efficacy. [Display omitted] [Display omitted] Disclosures:Flowers:Genentech/Biogen-Idec (unpaid): Consultancy; Celgene, Intellikine: Consultancy; Millennium: Research Funding; Otsuka: Research Funding. Waller:Otsuka: Research Funding.

Syntheses of Selenolato-Bridged Dinuclear Hydridoplatinum Complexes [Pt2H2(μ-SetBu)2(PPh3)2] and [Pt2H(SetBu)(μ-SetBu)2(PPh3)2]: Unusual Thermal Reaction of Hydrido(1,1-Dimethylethaneselenolato) Platinum Complex cis-[PtH(SetBu)(PPh3)2

Novel selenolato-bridged dinuclear hydridoplatinum complexes, cis-[Pt(2)H(2)(mu-Se(t)Bu)(2)(PPh(3))(2)] (2) and cis-[Pt(2)H(Se(t)Bu)(mu-Se(t)Bu)(2)(PPh(3))(2)] (3) were synthesized in 30% and 57% yields, respectively, by the thermolysis of hydrido(1,1-dimethylethaneselenolato) Pt(II) complex cis-[PtH(Se(t)Bu)(PPh(3))(2)] (1) in toluene at 80 degrees C for 3 h. The structures of dinuclear complexes 2 and 3 were fully characterized on the basis of their NMR and IR spectroscopic data and X-ray crystallography. The two distorted square planar Pt atoms in 2 and 3 are held together by two bridged selenolato ligands, (t)Bu groups of which adopt a trans configuration with respect to the four-membered Pt(2)Se(2) ring. Each central Pt(2)Se(2) ring in 2 and 3 has a hinged arrangement due to the steric repulsion among the two PPh(3) ligands and the (t)Bu group lying between them.

경남 일부 지역 여자 대학생의 상하체 균형 계측치와 운동 습관

경남지역 모 대학교에 재학 중인 여자 대학생 212명을 대상으로 인체 계측과 건강에 관련된 습관에 대하여 설문 조사를 실시하였다. 총대상자의 평균 연령은 20.7 세, 신장은 161.8 cm, 체중은 53.5 kg이었으며, 비만도는 98.4%이었으며 체질량 지수는 <TEX>$20.6\;kg/m^2$</TEX>이었고 허리-엉덩이 둘레 비율은 0.80이었다. 이와 같은 신체 계측치는 한국인의 정상 범위에 속하는 것이지만, 조사 대상자의 63.7%가 상체가 하체에 비하여서 불균형적으로 약한 체형인 것으로 나타났다. 이들 대상자를 불균형적으로 상체가 약한 군(UU, n=135)으로 하고 대조군으로써 상 하체가 균형인 군(BU, n=77)의 두 군으로 나누어서 측정 결과치를 비교 분석하였다. 체중, 비만도, 체질량지수, 허리-엉덩이 둘레비가 BU군에 비하여서 UU군이 유의적으로 낮았다. 체단백질, 체지방, 체무기질량도 역시 UU군에서 유의적으로 낮았다. 상완근육 둘레를 측정한 결과, UU군이 BU군에 비하여 유의적으로 낮았다. 운동의 규칙적 수행 여부를 알아본 결과 UU군의 1.5%, BU군에서 7.8%가 '운동을 규칙적으로 하고 있다'고 답하였다. 한편 '운동을 전혀 하고 있지 않다'라고 답한 비율이 UU군과 BU군에서 각각 55.5%, 31.2%로써, 운동을 하지 않는 경우가 UU군에서 1.8배 정도 많았다. 운동을 할 경우에 얼마나 오래하는지에 대한 질문에 UU군의 38.4%와 BU군의 35.8%가 30분 이하로 운동을 한다고 답하여서, 여자 대학생이 운동을 한다 하더라도 운동 시간이 충분하지 않은 것으로 사료된다. 본 연구 조사 결과, 상체가 하체에 비하여서 불균형적으로 약한 여자 대학생이 총 조사 대상자의 63.7%이나 되었으며, 이들의 운동 습관에 문제가 있는 것으로 나타나서 운동을 습관화하여 꾸준히 하고 특히 상체와 팔 근육을 발달시키는 운동을 실천하는 것이 필요하다고 사료된다. 아울러 여자 대학생만을 대상으로 하여 체형의 올바른 인식을 위한 교육의 필요성이 절실하며, 신체 부위의 균형을 고려한 운동 프로그램 개발이 시급하다고 생각한다. This study was carried out to examine anthropometric parameters and related habits in female college students. Mean age, height, and body weight of the subjects in total (n=212) were 20.7 yrs, 161.8 cm, and 53.5 kg, respectively. Anthropometric parameters were measured by bioelectrical impedance analysis. Mean degree of obesity, body mass index (BMI), and waist-hip ratio (WHR) were 98.4%, <TEX>$20.6\;kg/m^2$</TEX>, and 0.80 respectively. Surprisingly, 63.7% of the subjects showed unbalanced weak upper bodies compared to their lower bodies. Therefore, they were divided into two groups: unbalanced weak upper body group (UU, n=135) and balanced upper body groups (BU, n=77). Bodyweight, degree of obesity, BMI, and WHR in the UU group were significantly lower than those in the BU group. Amounts of body protein, body fat, and body mineral in the UU group were also significantly lower than those of the BU group. Mid-arm muscle circumference of the UU group (<TEX>$18.5{\pm}0.8\;cm$</TEX>) was significantly lower than those of BU group (<TEX>$20.4{\pm}1.2\;cm$</TEX>), although mid-arm circumference of the UU group was not significantly different compared to those of the BU group. On a questionnaire on exercise habits, 1.5% of the UU group and 7.8% of the BU group answered that they exercised regularly, and 55.5% of the UU group and 31.2% of the BU group reported that they never exercised (p<0.01). Even in the subjects who exercised, the duration of the exercise was not sufficient because 38.4% of the UU group and 35.8% of the BU group answered that they exercised for less than 30 min. In conclusion, interventions in exercise habits may be needed for female college students who have unbalanced weak upper bodies.

New insights into addition reactions of dialkylzinc reagents to trifluoromethyl ketones: Structural authentication of a β-hydride elimination product containing a tetranuclear zinc chain

A systematic study of the stoichiometric alkylation reactions of 2,2,2-trifluoroacetophenone 1 with [ZnR(2)(TMEDA)] (R= Me, Et, (t)Bu, CH(2)SiMe(3); TMEDA= N,N,N',N'-tetramethylethylenediamine) monitored by (1)H and (19)F NMR spectroscopy is presented. For R = Me, Et the alkylation products alkyl(alkoxides) [(TMEDA)Zn(R){OC(CF(3))(R)Ph}] (R = Me, 2: Et, 3) are obtained as the single products of the reaction. When the steric bulk of the dialkylzinc reagent is increased the alkylation reaction is inhibited. Thus, for R = (t)Bu, the reduction product [(TMEDA)Zn((t)Bu){OC(CF(3))(H)Ph}] is obtained as a result of beta-hydride elimination from one of the (t)Bu groups of the organometallic reagent. (1)H NMR spectroscopic monitoring of the reaction allowed the detection of isobutene as a side product of this reduction process. For the highly sterically demanding group R = CH(2)SiMe(3) which lacks hydrogen atoms at the beta position, no reaction is observed even under refluxing conditions. Two important intermediates from these reactions have been structurally elucidated: [(TMEDA)Zn(Me){OC(CF(3))(Me)Ph}] (2) which could be involved in the previously reported alkylation reaction of trifluoromethyl ketones by ZnR(2) catalysed by TMEDA and unprecedented tetranuclear [((t)Bu)(2)Zn(4){OC(CF(3))(H)Ph}(6)] (5) resulting from the reduction of 1 when reacted with (t)Bu(2)Zn, which displays a rare Zn...Zn...Zn...Zn linear chain arrangement for a zinc alkyl(alkoxide).

Structural studies of diorganotin(IV) sulfonates: The synthesis of [(n-C4H9)2Sn{OSO2C6H3(CH3)2-2,5}2] and [(n-C4H9)2Sn{OSO2R)2·2(hexamethylphosphoric triamide)] [R=CH3, 4-C6H4CH3, 2,5-C6H3(CH3)2, 2,4,6-C6H2(CH3)3] and crystal structures of [(n-C4H9)2Sn(μ-OH)(OSO2C6H3(CH3)2-2,5)]2 and (n-C4H9)2Sn{OSO2R)2·2(hexamethylphosphoric triamide)] [R=4-C6H4CH3, 2,5-C6H3(CH3)2, 2,4,6-C6H2(CH3)3

Reaction of ( n -C 4 H 9 ) 2 SnO with 2,5-dimethylbenzenesulphonic acid yields [( n -C 4 H 9 ) 2 Sn{OSO 2 C 6 H 3 (CH 3 ) 2 - 2 , 5 } 2 ] which on crystallization yields a dimeric compound [( n -C 4 H 9 ) 2 Sn(μ-OH)(OSO 2 C 6 H 3 (CH 3 ) 2 - 2 , 5 )] 2 containing bridging hydroxyl groups between Sn atoms and covalently bonded sulfonate anions. The syntheses of [( n -C 4 H 9 ) 2 Sn{OSO 2 C 6 H 3 (CH 3 ) 2 - 2 , 5 } 2 ] ( 1 ) and [( n -C 4 H 9 ) 2 Sn{OSO 2 R) 2 · 2HMPA] [R = CH 3 ( 3 ) , 4 -C 6 H 4 CH 3 ( 4 ), 2 , 5 -C 6 H 3 (CH 3 ) 2 ( 5 ), 2 , 4 , 6 -C 6 H 2 (CH 3 ) 3 ( 6 )] have been carried out to study their structures and to delineate the coordination behavior of the weakly coordinating sulfonate anions. Compound 1 hydrolyzes slowly to [( n -C 4 H 9 ) 2 Sn(μ-OH)(OSO 2 C 6 H 3 (CH 3 ) 2 - 2 , 5 )] 2 ( 2 ) when kept in CH 2 Cl 2 for a few days. The crystal structure shows that 2 has a dimeric structure in which tin atoms are bridged by two hydroxy groups and each tin atom is further bonded to two n -Bu groups and a mono-coordinated sulfonate anion thus generating a trigonal bipyramidal geometry at tin atom. However, the coordination geometry at tin can be visualized as a severely distorted octahedron, if a relatively weak Sn–O bond of 2.690 Å between Sn and an O atom of the neighboring sulfonate anion is also considered. Compounds 3–6 are obtained by the consecutive reaction of ( n -C 4 H 9 ) 2 SnO with the appropriate sulphonic acid and hexamethylphosphoric triamide (HMPA). X-ray crystal structures of 4, 5 and 6 s how octahedral geometry around tin atom in the two compounds in which the sulfonate ligands are covalently bonded in a monodentate mode. Compounds 3–6 are nonionic in polar solvents. The Sn–O (sulfonate) bond distances 2.354(2), 2 ; 2.233(2), 4 ; 2.237(5), 5 and 2.227(3) Å, 6 suggest some degree of ionic character in the metal-anion bonds. These compounds have also been characterized by multinuclear ( 1 H, 13 C and 119 Sn) NMR studies.

Surprising isomer preference on IrIII, favoring facile H–C(sp3) bond cleavage

Species (PNP)Ir(X)(Y), where PNP = N(SiMe(2)CH(2)P(t)Bu(2))(2)(-1) with X and Y halide, have a (t)Bu group C-H bond heterolytically split by addition across the Ir-N bond.

Chemistry of BDI*M(2+) complexes (M = Mg, Zn) and their role in lactide polymerization where BDI* is the anion derived from methylenebis(C-tBu, N-2,6-diisopropylphenyl)imine BDI*H

The bulky diimine CH(2){C((t)Bu)N-2,6-Pr(i)(2)C(6)H(3)}(2), BDI*H, is shown to exist in two isomers trans-trans, 1a and cis-trans, 1b that interconvert slowly on the NMR time-scale. Treatment of the diimine with (n)BuLi in hexane proceeds slowly to give the lithium beta-diketoiminate LiBDI*, 2, which upon hydrolysis yields the eneimine tautomer of BDI*H which has been characterized by X-ray studies in three rotamers, 3a, 3b and 3c. Dialkylmetal compounds (M = Mg, R = Bu; M = Zn, R = Et) react with either 1 or 3 in hydrocarbon and ether solvents to give BDI*Mg((n)Bu)THF, 4, and BDI*ZnEt, 5, which have been structurally characterized. M(N(SiMe(3))(2))(2) compounds where M = Mg, Zn or Ca failed to react with either 1 or 3 in hydrocarbon solvents. The reactions between ZnCl(2) and 2 yield BDI*ZnCl, 6, and a further reaction with LiNMe(2) yields BDI*ZnNMe(2), 7. The compounds 5 and 6 are shown to contain trigonal planar, M(2+) ions. Compounds 4, and 7 initiate ring-opening polymerization, ROP, of rac-lactide to give atactic polylactide, PLA. The rate of ROP depends on the metal M = Mg > Zn and is slower than that observed for the related beta-diketoiminate complexes where the bulky-(t)Bu group is replaced by Me.

A Triphenylene-Based Triptycene with Large Free Volume Synthesized by Zirconium-Mediated Biphenylation

Biphenylation using (Li(THF)(4))(2) x Zr(biphe)(3) of hexabromotriptycenes bearing H (1-H) or Bu (1-Bu) at the bridgeheads gave triptycenes with triphenylene blades. The blades extend both perpendicular and parallel to the 3-fold axis and generate a large intramolecular free volume (IMFV) (1-H, AM1, 710 A(3); cf. triptycene, AM1 71 A(3)). Crystals of 1-H could not be obtained. Triptycene 1-Bu, in which the Bu groups fill the voids near the bridgehead, was crystalline. X-ray diffraction analysis revealed crystal packing with alternating, interlocked corrugated and distorted hexagonal layers.

Height growth during adolescence and final height after haematopoietic SCT for childhood acute leukaemia: the impact of a conditioning regimen with BU or TBI

We compared the impact of a conditioning regimen with BU (n=16) or fractionated TBI (n=42) on height growth during adolescence and final height (FH), in 58 adults transplanted for acute leukaemia before adolescence (younger than 9 for girls and 11 for boys, and prepubertal). Heights were measured at three key periods, that is, transplantation, before adolescence, and FH, and compared using height standard deviation score (SDS) and cumulative change in SDS. The influence of the conditioning regimen was assessed using multiple linear regression and adjusting for gender, central nervous system irradiation, age and leukaemia status at transplant and type of transplantation. Overall mean height SDS was near normal at transplantation and before adolescence (0.2+/-0.1 and -0.2+/-0.1, respectively), but decreased to -1.6+/-0.1 at FH. There were significant differences between the TBI and BU groups when comparing FH SDS (-1.8+/-0.2 vs -0.8+/-0.2, P=0.001), mean change in height SDS from transplantation to FH (-2+/-0.1 vs -1.1+/-0.2, P=0.002) and mean change in height SDS during adolescence (-1.6+/-0.1 vs -0.7+/-0.2, P=0.003). We conclude that preparations involving BU, although less toxic than TBI-containing regimens, also have adverse effects on growth, predominantly during adolescence.

Impact of Conditioning Regimen in Allogeneic Hematopoetic Stem Cell Tansplant for Children with AML beyond the First Complete Remission: Total Body Irradiation Versus Busulfan- a Pediatric Blood and Marrow Transplant Consortium (PBMTC) Study

Busulfan (Bu) based preparative regimen is the most commonly used regimen for children with AML in 1st complete remission (CR). However conditioning regimens for children with AML beyond the first clinical remission (≥ 2nd CR) often include total body irradiation (TBI), which may result in significant long term sequelae. There are limited data concerning outcome in children with AML beyond 1st CR and no data comparing conditioning regimens in this population. One hundred fifty-one patients ≤ 21 years with AML in ≥ CR2 were included in this study. These patients were treated at 47 pediatric transplant centers between 2000 and 2007 with complete data forms reported to the PBMTC database. The median follow up was 2.6 years (range 0.25–8.02). One hundred thirty-four (92%) were in CR2 with a median age 9.2 years (range 0.8–21.6). Ninety (60%) received TBI based regimens and 61 (40%) received Bu based regimens. A majority of those patients received TBI or Bu in combination with cyclophosphamide. Twenty-six (17%) received related donor transplants and 125 (83%) received stem cells from unrelated sources. Thirty nine percent of patients received cord blood transplants. AML was considered high risk in 4 (3%) patients, intermediate risk in 98 (82%) and low risk in 17 (14%). The median time between CR1 and relapse was 12 months (range 1–60) and from achieving 2nd CR to transplant was 1.5 months (range 0.23–10.4). There were no significant differences between patients receiving TBI and Bu conditioning regimens with respect to age, sex, disease risk, pretransplant performance score, duration of CR1, time from CR2 to transplant and stem cell or donor source. There were significantly more patients with history of extramedullary disease in the TBI group (36% vs. 18%, p=0.02). Transplant related mortality (TRM) was not significantly different between the TBI and Bu groups (22% vs. 16%, p=0.29). Infection was the most common cause of death accounting for 39 % of the overall TRM. The probability of relapse at 2 years was 26% and 27% in the TBI and Bu groups, respectively, and it was not significantly different (p=0.93). The probability of progression free survival (PFS) and overall survival (OS) at 2 years was 55% and 56 % respectively. There was no difference in PFS (p=0.29) or OS (p=0.11) between the 2 groups. A multivariable analysis was performed including patients age, donor relation (related versus unrelated), presence of extramedullary disease, donor sex, duration of CR1, time from CR2 to transplant, presence of HLA mismatch and use of TBI. Longer duration of CR1 was associated with improved OS (HR=0.93, 0.90 – 0.97, p<0.001) and PFS (HR=0.94, 0.91 – 0.97, p<0.001). Longer time from CR2 to transplant decreased OS (HR=1.28, 1.07 – 1.53, p=0.007) and PFS (HR=1.21, 1.02 – 1.44, p=0.033). Receiving a transplant from HLA mismatched donor decreased OS (HR=2.04, 1.07 – 3.86, p=0.030) and PFS (HR=2.04, 1.10 – 3.77, p=0.024). The use of TBI was not associated with improved PFS (HR=1.18, 0.66–2.11, p=0.58) or OS (HR=1.42, 0.77–2.65, p=0.27). Shorter duration of first complete remission, longer time from second remission to transplant and receiving HLA mismatched allogeneic transplant adversely affected PFS and OS. Our study provided no evidence of an advantage to using TBI in children with AML beyond first complete remission.

Synthesis and structural characterisation of gallium and indium fluoroalkoxide ‘ate’ complexes

The treatment of InCl 3 with MOCH(CF 3) 2 (M = Li, Na, K) in a 1:6 stoichiometry, followed by recrystallisation results in the formation of the bimetallic “ate” complexes [Na 3In(OCH(CF 3) 2) 6(THF) 3] ( 2) and [Li 3In(OCH(CF 3) 2) 6(THF) 3] ( 5) from hexane, and [K 3In(OCH(CF 3) 2) 6] n ( 4) from a THF and toluene mixture. If a 1:3 stoichiometry is used chloride containing compounds [Na 2InCl(OCH(CF 3) 2) 4(THF) 4] ( 1) and [KInCl 2 (OCH(CF 3) 2) 2(THF) 3] n · THF ( 3) are obtained on recrystallisation from hexane. Treatment of GaCl 3 with 6 equivalents of LiOC(CH 3) 2CF 3 gives [LiGa(OC(CH 3) 2CF 3) 4(THF) 2] ( 6) on recrystallisation from hexane. The protolysis reaction between In(N(SiMe 3) 2) 3, formed in situ from (Me 3Si) 2NH, n BuLi and Incl 3, and HOCH(CH 3)CF 3 results in isolation of [LiIn(OCH(CH 3)CF 3) 3Bu] 2 ( 7) from hexane. The structures of 2, 4, and 5 all contain the tetranuclear core InO 6M 3. Compounds 1 and 3 have residual chloride; 1 is a trinuclear species with two THF ligands per Na, while 3 is a linear polymer. Compound 6 has a GaO 2Li four-membered parallelogram at its core. Complex 7 has a tetranuclear In 2O 6Li 2 core and an unexpected n Bu group on the In atoms. The coordination spheres of the alkali metals in 1– 6 include solvated THF while 1– 5 display additional close M⋯F interactions.

Synthesis, Structures, and Solution Dynamics of Palladium Complexes of Quinoline-Functionalized N-Heterocyclic Carbenes

A new type of quinoline-functionalized palladium N-heterocyclic carbene (NHC) complexes has been synthesized via silver transmetallation. The quinoline moiety was either directly attached to the imidazole ring or linked to it by a methylene group. NHCs with a methylene linker tend to form trans biscarbene complexes in the reaction of Pd(COD)Cl2, while NHCs without any linker form chelating NHC-quinoline (NHC-N) complexes. These two types of carbenes also react with [Pd(allyl)Cl]2 to give monodentate NHC palladium eta(3)-allyl chlorides [Pd(NHC)(allyl)Cl]. Fluxionality in the NMR time scale was observed for most complexes, and the origin of their dynamic behaviors was discussed for each type of structure. For [Pd(NHC)(allyl)Cl] with a relatively small wing tip group of the NHC, the fluxionality (selective line-broadening of (1)H NMR signals) is caused by selective eta(3)-eta(1)-eta(3) allyl isomerization. For NHC with a bulkier (t)Bu group, a different line-broadening pattern was observed and was ascribed to partially hindered Pd-C(carbene) bond rotation. For cationic chelating complexes [Pd(NHC-N)(allyl)]BF4, the dynamic exchange process likely originates from a dissociative boat-to-boat inversion of 7-membered palladacycles. Activation parameters were measured for this process. Crystal structures were reported for representative complexes in each category.

Neuropsychological outcome in very young hematopoietic SCT recipients in relation to pretransplant conditioning

Stem cell transplantation involves conditioning with TBI and/or intensive chemotherapy, which may cause long-term neuropsychological deficits, particularly in children treated at a very young age. The aim of this study was to investigate whether very young children who receive chemotherapy-based conditioning only (BUCY) may have a more favorable neuropsychological outcome than children conditioned with TBI-CY. Twenty-two children who underwent allogeneic SCT at 0.4-3.6 years of age were subject to an extensive neuropsychological assessment at an average of 6.5 years post-therapy. The test results of 10 children exposed to BU were compared to the results of 12 children who had received TBI. Ten of them had received single-dose TBI, whereas two had received fractionated TBI. The BU group performed at age level on verbal measures, but tended to score below age level in the executive and visuo-spatial domains (P<0.01). By comparison, children treated with TBI had more pervasive neuropsychological impairments, including motor deficits (P<0.01) and varying degrees of perceptual (P<0.05), executive and cognitive (P<0.05) problems. In conclusion, children transplanted at a very young age had a more favorable neuropsychological development if conditioned with BUCY than if conditioned with single-dose TBI-CY.

Stability of [MeBu3N][Tf2N] under gamma irradiation

The stability of the ionic liquid [MeBu3N][Tf2N], dry or after contact with water (where [MeBu3N]+ is the methyltributylammonium cation and [Tf2N](-) is the bistriflimide anion), was studied under 137Cs gamma irradiation in argon and in air. In a quantitative study with an absorbed dose of 2 MGy this ionic liquid was highly stable regardless of the radiolysis conditions. The radiolytic disappearance yields determined by ESI-MS were -0.38 and -0.25 micromol J(-1) for the cation and anion, respectively. ESI-MS, NMR, and liquid chromatography coupled with ESI-MS identified a large number of degradation products in very small quantities for the same dose. The cation radicals were formed by the loss of a Bu group, the Me group, or two H atoms to form a double bond with the butyl chain. Radiolysis of the anion produced mainly F and CF3 radicals. The anion radicals recombined with the cation to form a wide range of secondary degradation products regardless of the radiolysis conditions.