bluuebunny/crossref_metadata_2025 huggingface dataset:
Fused Polycyclic Nitrogen‐Containing Heterocycles. Part 9. Synthesis and Molecular Structure of Methyl 3‐(2‐R‐5‐Phenylthiazol‐4‐yl)‐7‐phenyl‐7H‐[1,2,4]triazolo[3,4‐b] [1,3,4]thiadiazine‐6‐carboxylates.
Authors: Mamedov V. A. , Mustakimova L. V. , Gubaidullin A. T. , Litvinov I. A. , Levin Ya. A.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Terpenoids and Related Compounds. Part 36. Eupacannol, a Pentacyclic Triterpene of a New Skeletal Type, and Other Chemical Constituents from Eupatorium cannabinum.
Authors: Talapatra Sunil Kumar , Bhar Durga Sankar , Chakraborti Ramaprasad , Talapatra Beni
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
ent‐Clerodanoids from Isodon scoparius
Authors: Xiang Wei , Li Rong‐Tao , Song Qi‐Shi , Na Zhi , Sun Han‐Dong
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Total Synthesis of Anachelin H
Authors: Gademann Karl , Bethuel Yann
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Synthesis of a Fluorescent Sulfatide for the Study of CD1 Antigen Binding Properties.
Authors: Franchini Laura , Compostella Federica , Donda Alena , Mori Lucia , Colombo Diego , De Libero Gennaro , Matto Pamela , Ronchetti Fiamma , Panza Luigi
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
A Novel Clean Catalytic Method for Waste‐Free Modification of Polysaccharides by Oxidation.
Authors: Kachkarova‐Sorokina Svetlana L. , Gallezot Pierre , Sorokin Alexander B.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Crystallographic and NMR Studies of Antiinfective Tricyclic Guanidine Alkaloids from the Sponge Monanchora unguifera
Authors: Hua Hui‐ming , Peng Jiangnan , Fronczek Frank R. , Kelly Michelle , Hamann Mark T.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
A New Dimeric Carbazole Alkaloid from Glycosmis stenocarpa Roots
Authors: Cuong Nguyen Manh , Hung Tran Quang , Sung Tran Van , Taylor Walter Chacles
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
A New Synthesis Analogue of Thymidine, 7‐(3‐Bromo‐phenoxy)‐thymidine, Inhibits the Proliferation of Tumor Cells.
Authors: Kim Kyung Noo , Lee Jiyong , Kim Dong Hoon , Yoo Jong‐Shin , Kwon Ho Jeong
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Chemical Constituents of a Marine Soft Coral of the Genus Lobophytum.
Authors: Radhika Parvataneni , Rao Vadali Lakshmana , Laatsch Hartmut
Published: March 2005

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New Diels—Alder Type Adducts from Morus macroura and Their Antioxidant Activities.
Authors: Dai Sheng‐Jun , Wu Yan , Wang Ying‐Hong , He Wen‐Yi , Chen Ruo‐Yun , Yu De‐Quan
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Use of a Chiral Praseodymium Shift Reagent in Predicting the Complete Stereostructure of Glisoprenin A
Authors: Ghosh Indranath , Kishi Yoshito , Tomoda Hiroshi , Omura Satoshi
Published: March 2005

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Structure—Activity Relationship Study on 13‐Deoxytedanolide, a Highly Antitumor Macrolide from the Marine Sponge Mycale adhaerens.
Authors: Nishimura Shinichi , Matsunaga Shigeki , Yoshida Satoru , Nakao Yoichi , Hirota Hiroshi , Fusetani Nobuhiro
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Lytophilippines A—C: Novel Macrolactones from the Red Sea Hydroid Lytocarpus philippinus.
Authors: Rezanka Tomas , Hanus Lumir O. , Dembitsky Valery M.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Novel Diarylsulfonylurea Derivatives as Potent Antimitotic Agents.
Authors: Kim Semi , Park Ji Hyun , Koo Sun‐Young , Kim Jung In , Kim Min‐Hyeung , Kim Ji Eun , Jo Kiwon , Choi Hwan Geun , Lee Sung Bae , Jung Sang‐Hun
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Synthesis of New Diaryl and Dialkyl Diselenides as Potential Virucides and Antimicrobials.
Authors: Palus J. , Chojnacka M. , Piasecki E. , Zboinska E. , Mlochowski J.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Aminoimidazo[1,2‐a]pyridines as a New Structural Class of Cyclin‐Dependent Kinase Inhibitors. Part 1. Design, Synthesis, and Biological Evaluation.
Authors: Jaramillo Carlos , et al. et al.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Polyoxometalates: from Inorganic Chemistry to Materials Science
Authors: Casan‐Pastor Nieves , Gomez‐Romero Pedro
Published: March 2005

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Layered Double Hydroxides (LDHs)
Authors: Braterman Paul S. , Xu Zhi Ping , Yarberry Faith
Published: March 2005

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The Silver Complexes of Porphyrins, Corroles, and Carbaporphyrins: Silver in the Oxidation States II and III
Authors: Bruckner Christian
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Transition Metal Complexes with Bis(hydrazone) Ligands of 2,6‐Diacetylpyridine: Heptacoordination of 3d Metals
Authors: Ivanovic‐Burmazovic Ivana , Andjelkovic Katarina
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Metallo‐Silanols and Metallo‐Siloxanes. Part 27. Synthesis and Reactivity of Silicon Transition Metal Complexes. Part 55. Metallo‐Silanols — Precursors for the Generation of Novel Metallo‐Siloxanes and Metallo‐Heterosiloxanes
Authors: Hofmann Marco , Voegler Matthias , Schumacher Dirk , Malisch Wolfgang
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Agostic versus Hypervalent Si‐H Interactions in Half‐Sandwich Complexes of Nb and Ta
Authors: Merkulov Alexei A. , Nikonov Georgii I. , Mountford Philip
Published: March 2005

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Dendrimers and Gold Nanoparticles as exo‐Receptors Sensing Biologically Important Anions
Authors: Astruc Didier , Daniel Marie‐Christine , Ruiz Jaime
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Transition Metal Complexes in Organic Synthesis. Part 70. Synthesis of Biologically Active Carbazole Alkaloids Using Organometallic Chemistry
Authors: Knoelker Hans‐Joachim
Published: March 2005

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Development of Transition Metal Mediated Cyclopropanation Reactions
Authors: DelMonte Albert J. , Dowdy Eric D. , Watson Daniel J.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Efficient, Ecologically Benign, Aerobic Oxidation of Alcohols
Authors: Marko Istvan E. , Giles Paul R. , Tsukazaki Masao , Chelle‐Regnaut Isabelle , Gautier Arnaud , Dumeunier Raphael , Philippart Freddi , Doda Kanae , Mutonkole Jean‐Luc , Brown Stephen M. , et al. et al.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Organoborane Coupling Reactions (Suzuki Coupling)
Authors: Suzuki Akira
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Combinatorial Libraries for Drug Development
Authors: Lee Alice , Szewczyk Jason W. , Ellman Jonathan A.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Natural and Synthetic Cage Compounds Incorporating the 2,9,10‐Trioxatricyclo[4.3.1.03,8]decane Type Moiety
Authors: Stanoeva Elena , He Weidong , De Kimpe Norbert
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Recent Developments in the Transfer of Chirality within Enolate Alkylation Reactions
Authors: Eames Jason , Suggate Michael J.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Selectfluor: Mechanistic Insight and Applications
Authors: Nyffeler Paul T. , Gonzalez Duron Sergio , Burkart Michael D. , Vincent Stephane P. , Wong Chi‐Huey
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
β‐Elimination Reactions by Using Samarium Diiodide
Authors: Concellon Jose M. , Rodriguez‐Solla Humberto
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Survey of Briarane‐Related Diterpenoids. Part 2
Authors: Sung Ping‐Jyun , Chang Pi‐Chen , Fang Lee‐Shing , Sheu Jyh‐Horng , Chen Wei‐Chen , Chen Yu‐Pei , Lin Mei‐Ru
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Pauson—Khand Reactions of Alkenyl Sulfones and Alkenyl Sulfoxides: Applications in Asymmetric Synthesis
Authors: Rivero Marta Rodriguez , Adrio Javier , Carretero Juan Carlos
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Synthesis, Structure, and Reactivity of Novel Oligomeric Titanasiloxanes
Authors: Jutzi Peter , Lindemann Hans Martin , Nolte Joern‐Oliver , Schneider Manuela
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Higher‐Coordinate Silicon Compounds with SiO5 and SiO6 Skeletons
Authors: Tacke Reinhold , Seiler Oliver
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
New Chiral Anion Mediated Asymmetric Chemistry
Authors: Lacour Jerome , Frantz Richard
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Continuous Solid‐State Polycondensation of Polyesters
Authors: Culbert B. , Christel A.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Quaternary Benzo[c]phenanthridine Alkaloids: Biological Activities
Authors: Simanek V. , Vespalec R. , Sedo A. , Ulrichova J. , Vicar J.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
One Sulfur, Selenium, or Tellurium Atom and One Nitrogen or Phosphorus Atom
Authors: Ulrich H.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Control of Hepatitis C: A Medicinal Chemistry Perspective
Authors: Gordon Christopher P. , Keller Paul A.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Synthetic Glycopeptides and Glycoproteins as Tools for Biology
Authors: Pratt Matthew R. , Bertozzi Carolyn R.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Noncovalent Binding Between Guanidinium and Anionic Groups: Focus on Biological‐ and Synthetic‐Based Arginine/Guanidinium Interactions with Phosph[on]ate and Sulf[on]ate Residues.
Authors: Schug Kevin A. , Lindner Wolfgang
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
“Molecular Photography”: Velocity‐Map Imaging of Chemical Events
Authors: Vallance Claire
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
New Chemistry on Old CDs
Authors: Yu Hua‐Zhong
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Chemosensitization by STI571 targeting the platelet‐derived growth factor/platelet‐derived growth factor receptor‐signaling pathway in the tumor progression and angiogenesis of gastric carcinoma
Authors: Kim Ryungsa , Emi Manabu , Arihiro Koji , Tanabe Kazuaki , Uchida Yoko , Toge Tetsuya
Published: March 2005

BACKGROUND

Autocrine and paracrine growth mediated by the platelet‐derived growth factor (PDGF)/PDGF receptor (PDGFR)‐signaling pathway plays an important role in the progression of solid tumors. The authors assessed the effect of STI571 on the tumor growth of gastric carcinoma in combination with 5‐fluorouracil (5‐FU) or paclitaxel targeting the PDGF/PDGFR‐signaling pathway.

METHODS

In MKN‐45 gastric carcinoma cells, the cytotoxic effect was evaluated by 3‐(4,5 dimethiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay, and the in vivo antitumor effect was evaluated in a nude mouse xenograft. Both STI571 and an antitumor drug were administered intraperitoneally. Gene expression was assessed by Western blot analysis and immunohistochemical staining. Apoptotic cell death was evaluated by the terminal deoxyuridine triphosphate‐biotin nick‐end labeling assay, and tumor angiogenesis was evaluated by microvessel density analysis.

RESULTS

Treatment with STI571 alone was not effective in vitro, as assessed by a 50% inhibitory concentration value of 24.3 μM. Combination treatment with STI571 and 5‐FU or paclitaxel enhanced the cytotoxic effect somewhat when the concentration of STI571 was increased to 10 μM. Combination treatment with STI571 and 5‐FU or paclitaxel enhanced the antitumor effect of the antitumor drug significantly in vivo. The enhanced antitumor effect was associated with increased apoptotic cell death and inhibition of tumor angiogenesis. Treatment with STI571 down‐regulated the expression of PDGF‐BB and PDGFR‐β in tumor cells and decreased the production of phosphorylated PDGFR‐β and phosphorylated Akt. Furthermore, treatment with STI571 inhibited the expression of PDGFR‐β in stromal cells.

CONCLUSIONS

STI571 was an effective chemosensitizer of antitumor drugs, such as 5‐FU and paclitaxel for gastric carcinoma, targeting the PDGF/PDGFR‐signaling pathway of tumor cells and stromal cells in disease progression and angiogenesis. Cancer 2005. © 2005 American Cancer Society.
Phase I/II trial of adding semisynthetic homoharringtonine in chronic myeloid leukemia patients who have achieved partial or complete cytogenetic response on imatinib
Authors: Marin David , Kaeda Jaspal S. , Andreasson Catharina , Saunders Sue M. , Bua Marco , Olavarria Eduardo , Goldman John M. , Apperley Jane F.
Published: March 2005

BACKGROUND

A Phase I/II study was designed to show whether the addition of semisynthetic homoharringtonine (sHHT) would reduce the level of residual disease in patients with Ph‐positive chronic myeloid leukemia who appeared to have achieved a suboptimal response to imatinib alone.

METHODS

Patients with CML who had achieved ≥ 35% Ph‐negativity on imatinib were included. All patients had been treated with imatinib at ≥ 400 mg/day for at least 2 years and had achieved a plateau in BCR‐ABL transcripts defined by measuring BCR‐ABL transcripts on at least 4 occasions over a minimum period of 1 year with the latest value not lower than the previous minimum value. Initially sHHT was given subcutaneously at a dose of 1.25 mg/m2 twice daily for 1 day. Courses were repeated every 28 days. The dosage of sHHT was escalated by adding one day of treatment every two days. Efficacy was assessed by serial monitoring of blood levels of BCR‐ABL transcripts.

RESULTS

Of 10 evaluable patients, 7 had an appreciable decline in BCR‐ABL transcript levels; in 5 cases the reduction was greater than 1 log. Asthenia (n = 10) and cytopenias (n = 3) were prominent side‐effects, but the drug was generally well tolerated. Mutations in the P‐loop of the BCR‐ABL kinase domain were found in 2 of the patients who responded to the addition of sHHT.

CONCLUSIONS

The addition of sHHT should be considered for patients on imatinib who fail to obtain low levels of minimal residual disease. Cancer 2005. © 2005 American Cancer Society.
Comparison of HER‐2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma
Authors: Gong Yun , Booser Daniel J. , Sneige Nour
Published: March 2005

BACKGROUND

Accurate assessment of HER‐2 status is necessary prior to anti‐HER‐2 antibody (trastuzumab) therapy for metastatic breast carcinoma. However, controversy exists regarding whether to assess HER‐2 status in the primary tumor or in metastatic lesions. It is also unclear whether HER‐2 status can change during disease progression or after chemotherapy.

METHODS

Breast carcinoma samples from 60 women with known HER‐2 status in both primary tumors and paired metastases (locoregional disease, n = 43 patients; distant disease, n = 17 patients) were reviewed retrospectively. Thirty‐two patients underwent chemotherapy before their metastatic lesions were sampled, including 18 patients who received neoadjuvant chemotherapy and 14 patients who received adjuvant chemotherapy. The HER‐2 gene was examined by fluorescence in situ hybridization either in paraffin‐embedded tissue samples (48 primary tumors and 9 metastatic tumors) or in fine‐needle aspirates (12 primary tumors and 51 metastatic tumors). HER‐2 gene amplification was defined as a HER‐2:chromosome 17 signal ratio ≥ 2.0.

RESULTS

The HER‐2 status of primary and metastatic tumors agreed in 58 of 60 patients (97%), including 18 (30%) amplified tumors and 40 (67%) nonamplified tumors. A discrepancy in HER‐2 status was observed in specimens from two patients in which HER‐2 amplification was detected in the primary tumor but not the metastatic tumors. In one patient, three foci of tumor nodules were found in the same breast; the HER‐2 status was assessed in only one of them, which showed amplification; however, HER‐2 amplification was not detected in the axillary lymph node metastasis. In another patient, the HER‐2 gene was amplified in the primary tumor but not in the liver metastasis. No metastases showed HER‐2 amplification without amplification in the primary tumor. Locoregional and distant metastases demonstrated similar concordance rates with their corresponding primary tumors (98% and 94%, respectively). Complete concordance of HER‐2 status was found between primary tumors prior to chemotherapy and metastases that were sampled after chemotherapy.

CONCLUSIONS

The HER‐2 status in breast carcinoma generally was stable during metastasis, whether to locoregional or distant sites. Chemotherapy did not modify the HER‐2 status in metastatic lesions. Therefore, HER‐2 amplification can be evaluated reliably in material from either primary or metastatic tumors in most patients. Further study with larger series is warranted to elucidate the significance of discordant results. Cancer 2005. © 2005 American Cancer Society.
Evaluating high‐performance computers
Authors: Vetter Jeffrey S. , de Supinski Bronis R. , Kissel Lynn , May John , Vaidya Sheila
Published: March 2005

Comparisons of high‐performance computers based on their peak floating point performance are common but seldom useful when comparing performance on real workloads. Factors that influence sustained performance extend beyond a system's floating‐point units, and real applications exercise machines in complex and diverse ways. Even when it is possible to compare systems based on their performance, other considerations affect which machine is best for a given organization. These include the cost, the facilities requirements (power, floorspace, etc.), the programming model, the existing code base, and so on. This paper describes some of the important measures for evaluating high‐performance computers. We present data for many of these metrics based on our experience at Lawrence Livermore National Laboratory (LLNL), and we compare them with published information on the Earth Simulator. We argue that evaluating systems involves far more than comparing benchmarks and acquisition costs. We show that evaluating systems often involves complex choices among a variety of factors that influence the value of a supercomputer to an organization, and that the high‐end computing community should view cost/performance comparisons of different architectures with skepticism. Published in 2005 by John Wiley & Sons, Ltd.
Architectural specification for massively parallel computers: an experience and measurement‐based approach
Authors: Brightwell Ron , Camp William , Cole Benjamin , DeBenedictis Erik , Leland Robert , Tomkins James , Maccabe Arthur B.
Published: March 2005

In this paper, we describe the hardware and software architecture of the Red Storm system developed at Sandia National Laboratories. We discuss the evolution of this architecture and provide reasons for the different choices that have been made. We contrast our approach of leveraging high‐volume, mass‐market commodity processors to that taken for the Earth Simulator. We present a comparison of benchmarks and application performance that support our approach. We also project the performance of Red Storm and the Earth Simulator. This projection indicates that the Red Storm architecture is a much more cost‐effective approach to massively parallel computing. Published in 2005 by John Wiley & Sons, Ltd.
T‐cell lymphoblastic leukemia/lymphoma syndrome with eosinophilia and acute myeloid leukemia
Authors: Lamb Lawrence S. , Neuberg Ronnie , Welsh Jeff , Best Robert , Stetler‐Stevenson Maryalice , Sorrell April
Published: March 2005

This case represents an example of an unusual T‐cell lymphoblastic leukemia/lymphoma syndrome associated with eosinophilia and myeloid malignancy in a young boy. This case is one of only five reported “leukemic” variants of the disease and demonstrates the importance of considering this poor prognostic diagnosis in pediatric acute lymphoblastic leukemia. This case also illustrates the importance of an interactive multidisciplinary approach to the laboratory evaluation of a leukemia patient. © 2005 Wiley‐Liss, Inc.
Slit‐flow ektacytometry: Laser diffraction in a slit rheometer
Authors: Shin Sehyun , Ku Yunhee , Park Myung‐Su , Suh Jang‐Soo
Published: March 2005

Background

Deformability of red blood cells (RBCs) is a determinant of blood flow resistance as RBCs pass through small capillaries of the microcirculation. Available techniques for measuring RBC deformability often require a washing process after each measurement, which is not optimal for day‐to‐day clinical use.

Methods

A laser diffraction technique has been combined with slit‐flow rheometry, which shows significant advances in ektacytometric design, operation, and data analysis. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element that is in contact with the blood sample.

Results

With slit ektacytometry, the deformation of RBCs subjected to continuously decreasing shear stress in a slit flow can be quickly measured with extremely small quantities of blood. The measurements with the slit ektacytometer were compared with those of LORCA and a strong correlation was apparent. The deformability of the hardened RBCs was markedly lower than that of the normal RBCs. In addition, the young cells showed higher values of the elongation index than did the old cells.

Conclusions

The newly developed slit ektacytometer can measure RBC deformability with ease and accuracy. In addition, the slit ektacytometer can be easily used in a clinical setting owing to the incorporation of a disposable element that holds the blood sample. © 2005 Wiley‐Liss, Inc.
Synthesis and Characterisation of New Iridium Complexes with the (4S)‐2‐[2‐(Diphenylphosphanyl)phenyl]‐4‐isopropyl‐1,3‐oxazoline Ligand That Catalyse Asymmetric Michael Reactions
Authors: Carmona Daniel , Ferrer Joaquina , Lorenzo Mónica , Lahoz Fernando J. , Dobrinovitch Isabel T. , Oro Luis A.
Published: March 2005

The chiral iridium compounds [IrCl(COE){(S)‐PN}] {COE = cyclooctene, PN = (4S)‐2‐[2‐(diphenylphosphanyl)phenyl]‐4‐isopropyl‐1,3‐oxazoline, (1)}, [Ir(acac)ClH{(S)‐PN}] {Hacac = acetylacetone, (2)} and [Ir{(S)‐PN}2]A {A = Cl (3a,b); BF4 (4a,b); PF6 (5a,b)} have been prepared, characterised and employed as catalysts for the asymmetric Michael addition of keto or cyano esters to α,β‐unsaturated carbonyl compounds. The X‐ray molecular structures of compounds 2 and 5b are reported. The model catalytic intermediates [IrH(NCCHCO2R){(S)‐PN}2]Cl {R = Me (12), Et (13)} have also been isolated and characterised. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Kinetics and Mechanism of the Demetallation of Macrocyclic Nickel(II) Complexes by Cyanide
Authors: Siegfried Liselotte , Kaden Thomas A.
Published: March 2005

The kinetics and the mechanism of the cyanide‐induced demetallation of a series of Ni2+ complexes with macrocyclic ligands of different ring size (12‐ to 14‐membered; see 1–4) and steric constraints was studied. Although the rates differ by almost five orders of magnitude when compared to each other under fixed experimental conditions (pH 10.5, [CN−]=10−2 M), all reactions proceed through the relatively rapid formation of cyano adducts [Ni(CN)nL] (n=1, 2), which then react with additional CN− or HCN to give the final products. Of paramount importance for the reaction rate is the geometry and configuration of the cyano adducts [Ni(CN)nL] (n=1,2). cis‐Dicyano derivatives with a folded macrocycle react faster than trans‐compounds. In the case of (1,4,8,11‐tetraazacyclotetradecane)nickel(2+) ([Ni (4)]2+), which gives a trans‐ dicyano adduct, the base‐catalyzed N‐inversion necessary to obtain the cis‐dicyano derivative becomes rate determining at high CN− concentrations.
S‐Functionalized Cysteine: Powerful Ligands for the Labelling of Bioactive Molecules with Triaquatricarbonyltechnetium‐99m(1+) ([99mTc(OH2)3(CO)3]+)
Authors: van Staveren Dave R. , Benny Paul D. , Waibel Robert , Kurz Philipp , Pak Jae‐Kyoung , Alberto Roger
Published: March 2005

S‐Alkylated cysteines are used as efficient tridentate N,O,S‐donor‐atom ligands for the fac‐[M(CO)3]+ moiety (M=99mTc or Re). Reaction of (Et4N)2[ReBr3(CO)3] (3) with the model S‐benzyl‐L‐cysteine (2) leads to the formation of [Re(2′)(CO)3] (4) as the exclusive product (2′=C‐terminal anion of 2). The tridentate nature of the alkylated cysteine in 4 was established by X‐ray crystallography. Compound 2 reacts with [99mTc(OH2)3(CO)3]+ under mild conditions (10−4 M, 50°, 30 min) to afford [99mTc(2′)(CO)3] (5) and represents, therefore, an efficient chelator for the labelling of biomolecules. L‐Cysteine, S‐alkylated with a 3‐aminopropyl group (→7), was conjugated via a peptide coupling sequence with Coα‐[α‐(5,6‐dimethyl‐1H‐benzimidazolyl)]‐Coβ‐cyanocobamic b‐acid (6), the b‐acid of cyanocob(III)alamin (vitamin B12) (Scheme 3). More convenient was a one‐pot procedure with a derivative of vitamin B12 comprising a free amine group at the b‐position. This amine 15 was treated with NHS (N‐hydroxysuccinimide)‐activated 1‐iodoacetic acid 14 to introduce an I‐substituent in vitamin B12. Subsequent addition of unprotected L‐cysteine resulted in nucleophilic displacement of the I‐atom by the S‐substituent, affording the vitamin B12 alkylated cysteine fragment 17 (Scheme 4). The procedure was quantitative and did not require purification of intermediates. Both cobalamin–cysteine conjugates could be efficiently labelled with [99mTc(OH2)3(CO)3]+ (1) under conditions identical to those of the model complex 5. Biodistribution studies of the cobalamin conjugates in mice bearing B10‐F16 melanoma tumors showed a tumor uptake of 8.1±0.6% and 4.4±0.5% injected dose per gram of tumor tissue after 4 h and 24 h, respectively (Table 1).
Water‐Exchange Mechanism for Zinc(II), Cadmium(II), and Mercury(II) Ions in Water as Studied by Umbrella‐Sampling Molecular‐Dynamics Simulations
Authors: Inada Yasuhiro , Mohammed Ahmed M. , Loeffler Hannes H. , Funahashi Shigenobu
Published: March 2005

Umbrella‐sampling molecular‐dynamics simulations were performed to investigate the water‐exchange reactions of zinc(II), cadmium(II), and mercury(II) ions in aqueous solution. The dissociation of a coordinating water molecule to the MO distance at 3.34, 3.16, and 3.26 Å for ZnII, CdII, and HgII, respectively, leads the system to a transition state. For ZnII, the first hydration shell is occupied by five spectator water molecules in the transition state, indicating that the water‐exchange reaction proceeds via a dissociative mode of activation. In contrast, the number of spectator water molecules of 5.85 and 5.95 for CdII and HgII, respectively, suggests an associative exchange for these larger metal ions. The average MO distance of the spectator molecules is shortened by 0.06 Å for the dissociative exchange of ZnII, while it is elongated by 0.04 and 0.03 Å for CdII and HgII, respectively. The water‐exchange rate constants of 4.1×108, 6.8×108, and 1.8×109 s−1 are estimated for ZnII, CdII, and HgII, respectively, at 298 K in terms of the transition‐state theory based on the assumption of a transmission coefficient of unity.
On the Adsorption, by Activated Carbons, of Some Sparingly Soluble Organics from Aqueous Solutions
Authors: Hugi‐Cleary Deirdre , Slasli Abdou , Stoeckli Fritz
Published: March 2005

Activated carbons play an important role in the purification of air and of water. Whereas vapors are adsorbed by a micropore filling process, the removal of sparingly soluble species such as phenol and its derivatives is limited to the coating of the effective surface of the material. This reduces considerably the sorptive capacity of a given carbon, and a suitable description is needed to predict the corresponding equilibrium. It is shown that, in the case of phenol, its derivatives, and a few typical pollutants, the latter process can be described by an extension of the Dubinin–Radushkevich–Kaganer (DRK) equation. A major advantage of this approach is the possibility of calculating the adsorption equilibrium based on simple physicochemical properties of the adsorptives and on the structural characteristics of the activated carbon. It also appears that, by analogy with adsorption in the vapor phase, a scaling factor can be introduced for adsorption from solution.
Square‐Planar Carbonylchlororhodium(I) Complexes Containing trans‐Spanning Diphosphine Ligands as Catalysts for the Carbonylation of Methanol
Authors: Burger Sylvain , Therrien Bruno , Süss‐Fink Georg
Published: March 2005

The rhodium(I) complexes trans‐[Rh(diphos)(CO)Cl] 7 (diphos=pbpb), 8 (diphos=nbpb), and 9 (diphos=cbpb) were synthesized (Scheme 4) and used as catalysts for the carbonylation of MeOH to AcOH (Scheme 1). The trans coordination imposed by the rigid C‐spacer framework of the diphos ligands pbpb, nbpb, and cbpb, demonstrated by 31P‐NMR and IR spectroscopy of 7–9 and unambiguously confirmed by single‐crystal X‐ray structure analysis of 7, improved the thermal stability of the rhodium(I) system under carbonylation conditions and, hence, the catalytic performance of the complexes. For the catalytic carbonylation of MeOH, the active catalyst could be prepared in situ from the mixture of [Rh(CO)2Cl]2 and the corresponding diphos ligand pbpb, nbpb, or cbpb, giving the same results as carbonylation in the presence of the isolated complexes 7, 8 or 9 (see Table). The highest activity was observed for complex 7 (or the mixture [Rh(CO)2Cl]2/pbpb, the catalytic turnover number (TON) being 950 after 15 min (170°, 22 bar).
Asymmetric Synthesis of Coordination Compounds: Back to the Roots. Diastereoselective Synthesis of Simple Platinum(IV) Complexes
Authors: Drahoňovský Dušan , von Zelewsky Alex
Published: March 2005

A publication by Alexander P. Smirnoff in Helvetica Chimica Acta in 1920 [6] describes the first synthesis of a coordination species, i.e., of tris(propane‐1,2‐diamine‐κN1,κN2)platinum(4+) ([PtIV(pn)3]4+), where it was shown that the configuration of a chiral center in the ligand can influence the configuration at the metal. The present investigation of [PtIV(pn)3]4+ was carried out by NMR spectroscopy, where all nuclei in the metal complex were used as sources of information, i.e., 1H, 13C, 15N, and 195Pt. 13C‐NMR and 15N‐NMR spectroscopy (of isotopically enriched complex) were especially informative for the analysis of isomer distribution. Stereoselectivity in the formation reaction of the complexes is rather modest, whereas Δ‐, and Λ‐isomers can be separated efficiently by crystallization. A mixture of [Pt{(S)‐pn}3]4+ and [Pt{(R)‐pn}3]4+ shows no scrambling of the enantiomeric ligands, thus proving the inertness of the complexes.
A Dissociative Route to CH Bond Activation: Ligand Cyclometalation in cis‐Dimethyl[(sulfinyl‐κS)bis[methane]][tris(2‐methylphenyl)phosphine]platinum(2+)
Authors: Romeo Raffaello , Plutino Maria Rosaria , Romeo Andrea
Published: March 2005

The dialkyl compound cis‐dimethyl[(sulfinyl‐κS)bis[methane]][tris(2‐methylphenyl)phosphine]platinum(2+) (cis‐[Pt(Me)2(dmso)(P(o‐tol)3]; 1) has been isolated from the reaction of cis‐dimethylbis[(sulfinyl‐κS)bis[methane]]platinum(2+) (cis‐[Pt(Me)2(dmso)2]) with tris(2‐methylphenyl)phosphane (P(o‐tol)3). Restricted rotation around the PCipso bonds of the phosphane ligand generates two different conformers, 1a and 1b, in rapid exchange in non‐polar solvents at low temperature. Strong through‐space contacts between the ortho‐Me substituent groups on the ligand and the cis‐Me groups in the coordination plane were determined, which proved useful for identifying the atropisomers formed. At room temperature, 1H‐NMR spectra of 1 maintain a ‘static’ pattern upon onset of easy and rapid ortho‐platination, leading to [[2‐[bis(2‐methylphenyl)phosphino‐κP]phenyl]methyl‐κC]methyl[(sulfinyl‐κS)bis[methane]]platinum(2+) (2), a new C,P‐cyclometalated compound of platinum(II), with liberation of methane. The process has been studied by 1H‐ and 31P{1H}‐NMR in CDCl3, and kinetics experiments were performed by conventional spectrophotometric techniques. The first‐order rate constants kc decrease with the addition of dimethyl sulfoxide until the process is blocked by the presence of a sufficient excess of sulfoxide. This behavior reveals a mechanism initiated by ligand dissociation and formation of a three‐coordinate species. The value of the rate constant for dimethyl sulfoxide dissociation k1 has been measured independently over a wide temperature range by both 1H‐NMR ligand exchange (isotopic labeling experiments) and ligand substitution (stopped‐flow pyridine for dimethyl sulfoxide substitution). The rates of the two processes are in reasonable agreement at the same temperature, and a single Eyring plot can be constructed with the two sets of kinetics data. However, the value of the derived dissociation constant at 308 K (k1=6.5±0.3 s−1) is at least two orders of magnitude higher than that of cyclometalation (kc=0.0098±0.0009 s−1 at 308 K). Clearly, the dissociation step is not rate‐determining for cyclometalation. A multistep mechanism consistent with mass‐law retardation is derived, which involves a pre‐equilibrium that controls the concentration of an unsaturated three‐coordinate, 14‐electron T‐shaped cis‐[PtMe2{P(o‐tol)3}] intermediate. Cyclometalation is initiated in this latter by an agostic interaction with the σ(CH) orbital of a methyl group. Oxidative addition of the CH bond follows, yielding a cyclometalated‐hydrido 16‐electron Pt(IV) five‐coordinate intermediate. Finally, reductive elimination and re‐entry of dimethyl sulfoxide with liberation of methane should yield the cyclometalated species 2.
Can the Theoretical Fitting of the Proton‐Nuclear‐Magnetic‐Relaxation‐Dispersion (Proton NMRD) Curves of Paramagnetic Complexes Be Improved by Independent Measurement of Their Self‐Diffusion Coefficients?
Authors: Vander Elst Luce , Sessoye Audrey , Laurent Sophie , Muller Robert N.
Published: March 2005

The self‐diffusion (Dc) coefficients of various lanthanum(III) diamagnetic analogues of open‐chain and macrocyclic complexes of gadolinium used as MRI contrast agents were determined in dilute aqueous solutions (3–31 mM) by pulsed‐field‐gradient (PFG) high‐resolution 1H‐NMR spectroscopy. The self‐diffusion coefficient of H2O (Dw) was obtained for the same samples to derive the relative diffusion constant, a parameter involved in the outersphere paramagnetic‐relaxation mechanism. The results agree with an averaged relative diffusion constant of 2.5 (±0.1)×10−9 and of 3.3 (±0.1)×10−9 m2 s−1 at 25 and 37°, respectively, for 'small' contrast agents (Mr 500–750 g/mol), and with the value of bulk H2O (2.2×10−9 and 2.9×10−9 m2 s−1 at 25° and at 37°, respectively) for larger complexes. The use of the measured values of Dc for the theoretical fitting of proton NMRD curves of gadolinium complexes shows that the rotational correlation times (τR) are very close to those already reported. However, differences in the electronic relaxation time (τSO) at very low field and in the correlation time (τV) related to electronic relaxation were found.
Gadolinium(III) Complexes of dota‐Derived N‐Sulfonylacetamides (H4(dota‐NHSO2R)=10‐{2‐[(R)sulfonylamino]‐2‐oxoethyl}‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic Acid): A New Class of Relaxation Agents for Magnetic Resonance Imaging Applications
Authors: Aime Silvio , Botta Mauro , Cravotto Giancarlo , Frullano Luca , Giovenzana Giovanni B. , Geninatti Crich Simonetta , Palmisano Giovanni , Sisti Massimo
Published: March 2005

Four new ligands for lanthanide ions based on the H3do3a (=1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid) structure and bearing one N‐sulfonylacetamide arm were synthesized, i.e., H4dota‐NHSO2R=10‐{2‐[(R)sulfonylamino]‐2‐oxoethyl}‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acids 1a–e. A 15N‐NMR study of the 15N‐labelled Eu3+ complex of one such ligands, 1d, showed that the coordination of the N‐sulfonylacetamide arm involves the carbonyl O‐atom rather than the N‐atom. The relaxometric properties of the corresponding Gd3+ complexes were investigated as a function of pH and temperature. These complexes have relaxivities in the range 4.5–5.3 mM−1 s−1, at 20 MHz and 25°, and are characterized by a single H2O molecule in their inner coordination sphere. The mean residence lifetime of this molecule is relatively long (500–700 ns) compared to other anionic complexes. The slow rate of H2O exchange can be justified by the extensive delocalization of the negative charge on the N‐sulfonylacetamide arm. The long residence time of the coordinated H2O allowed the observation of the effect of the prototropic exchange on the relaxivity. The study of the interaction between the complex [Gd(1e)]‐ and HSA revealed a weak affinity constant highlighting the importance of a localized negative charge on the complex to promote a strong interaction with the protein.
Complexation Properties of N,N′,N″,N′′′‐[1,4,7,10‐Tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(1‐oxoethane‐2,1‐diyl)]tetrakis[glycine] (H4dotagl). Equilibrium, Kinetic, and Relaxation Behavior of the Lanthanide(III) Complexes
Authors: Baranyai Zsolt , Brücher Ernő , Iványi Tímea , Király Róbert , Lázár István , Zékány László
Published: March 2005

Eu3+, Dy3+, and Yb3+ complexes of the dota‐derived tetramide N,N′,N″,N′′′‐[1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(1‐oxoethane‐2,1‐diyl)]tetrakis[glycine] (H4dotagl) are potential CEST contrast agents in MRI. In the [Ln(dotagl)] complexes, the Ln3+ ion is in the cage formed by the four ring N‐atoms and the amide O‐atom donor atoms, and a H2O molecule occupies the ninth coordination site. The stability constants of the [Ln(dotagl)] complexes are ca. 10 orders of magnitude lower than those of the [Ln(dota)] analogues (H4dota=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid). The free carboxylate groups in [Ln(dotagl)] are protonated in the pH range 1–5, resulting in mono‐, di‐, tri‐, and tetraprotonated species. Complexes with divalent metals (Mg2+, Ca2+, and Cu2+) are also of relatively low stability. At pH>8, Cu2+ forms a hydroxo complex; however, the amide H‐atom(s) does not dissociate due to the absence of anchor N‐atom(s), which is the result of the rigid structure of the ring. The relaxivities of [Gd(dotagl)] decrease from 10 to 25°, then increase between 30–50°. This unusual trend is interpreted with the low H2O‐exchange rate. The [Ln(dotagl)] complexes form slowly, via the equilibrium formation of a monoprotonated intermediate, which deprotonates and rearranges to the product in a slow, OH−‐catalyzed reaction. The formation rates are lower than those for the corresponding Ln(dota) complexes. The dissociation rate of [Eu(dotagl)] is directly proportional to [H+] (0.1–1.0M HClO4); the proton‐assisted dissociation rate is lower for [Eu(H4dotagl)] (k1=8.1⋅10−6 M−1 s−1) than for [Eu(dota)] (k1=1.4⋅10−5 M−1 s−1).
Structure and Dynamics of Lanthanide Complexes of Triethylenetetramine‐N,N,N′,N″,N′′′,N′′′‐hexaacetic Acid (H6ttha) and of Diamides H4ttha(NHR) Derived from H6ttha as Studied by NMR, NMRD, and EPR
Authors: Zitha‐Bovens Emrin , Muller Robert N. , Laurent Sophie , Vander Elst Luce , Geraldes Carlos F. G. C. , van Bekkum Herman , Peters Joop A.
Published: March 2005

A multinuclear NMR study on [Ln(ttha)]3− and [Ln{ttha(NHR)2}]− complexes (R=Et, CH2(CHOH)4CH2OH) shows that coordinating groups of the organic ligands in these complexes are occupying all coordination sites of the metal ions, leaving no space for coordination of H2O molecules (H6ttha=triethylenetetramine‐N,N,N′,N″,N′′′,N′′′‐hexaacetic acid). The lanthanides of the first half of the series bind the ttha‐type ligands in a decadentate fashion, while the complexes formed with the smaller ions of the second half of the lanthanide series are nonadentate. One carboxylate group of the ligand remains unbound in the latter complexes. In principle, the ttha complexes can exist in six enantiomeric forms. Only one of the pair of diastereoisomers can interconvert without decoordination of the ligand. This pair of isomers seems to be predominant in solution. For the [Ln{ttha(NHR)2}]− complexes, the number of chiral centers is larger, resulting in 32 possible enantiomeric forms of the complexes. The NMR spectra of [Nd{ttha(NHEt)2}]− indicate that two dynamic processes occur between the isomers in solution. The NMRD curves of [Gd(ttha)]3−, [Gd{ttha(NHEt)2}]−, and [Gd{ttha(NHgluca)2}]− (NHgluca=D‐glucamine) show significant differences with the previously determined outer‐sphere contributions to the NMRD profiles of the corresponding [Gd{dtpa(NHR)2}]− complexes, which can be ascribed to differences in the parameters determining the electronic relaxation.
Tuning the Properties of Copper(II) Complexes with Tetra‐ and Pentadentate Bispidine (=3,7‐Diazabicyclo[3.3.1]nonane) Ligands
Authors: Comba Peter , Lopez de Laorden Carlos , Pritzkow Hans
Published: March 2005

The synthesis of a series of tetra‐ and pentadentate bispidine‐type ligands (bispidine=3,7‐diazabicyclo[3.3.1]nonane) – tetradentate ligands are donor‐substituted at C(2) and C(4), pentadentate ligands have an additional donor at N(3) or N(7), with pyridine, 2‐methylpyridine, or quinoline donor moieties – and of their CuII complexes are reported, together with single‐crystal structural analyses and solution studies (electrochemistry, electronic and EPR spectroscopy). Depending on the ligand geometry and on the co‐ligands (solvent or counter anion), there are various structural forms (pseudo‐Jahn–Teller elongation along all three molecular axes), and the structural data are correlated with the spectroscopic and electrochemical parameters.
Novel P‐Stereogenic PCP Pincer‐Aryl Ruthenium(II) Complexes and Their Use in the Asymmetric Hydrogen Transfer Reaction of Acetophenone
Authors: Medici Serenella , Gagliardo Marcella , Williams Scott B. , Chase Preston A. , Gladiali Serafino , Lutz Martin , Spek Anthony L. , van Klink Gerard P. M. , van Koten Gerard
Published: March 2005

Achiral P‐donor pincer‐aryl ruthenium complexes ([RuCl(PCP)(PPh3)]) 4c,d were synthesized via transcyclometalation reactions by mixing equivalent amounts of [1,3‐phenylenebis(methylene)]bis[diisopropylphosphine] (2c) or [1,3‐phenylenebis(methylene)]bis[diphenylphosphine] (2d) and the N‐donor pincer‐aryl complex [RuCl{2,6‐(Me2NCH2)2C6H3}(PPh3)], (3; Scheme 2). The same synthetic procedure was successfully applied for the preparation of novel chiral P‐donor pincer‐aryl ruthenium complexes [RuCl(P*CP*)(PPh3)] 4a,b by reacting P‐stereogenic pincer‐arenes (S,S)‐[1,3‐phenylenebis(methylene)]bis[(alkyl)(phenyl)phosphines] 2a,b (alkyl=iPr or tBu, P*CHP*) and the complex [RuCl{2,6‐(Me2NCH2)2C6H3}(PPh3)], (3; Scheme 3). The crystal structures of achiral [RuCl(PCP)(PPh3)] 4c and of chiral (S,S)‐[RuCl(PCP)(PPh3)] 4a were determined by X‐ray diffraction (Fig. 3). Achiral [RuCl(PCP)(PPh3)] complexes and chiral [RuCl(P*CP*)(PPh3)] complexes were tested as catalyst in the H‐transfer reduction of acetophenone with propan‐2‐ol. With the chiral complexes, a modest enantioselectivity was obtained.
Improvement of the bond strength of 4‐META/MMA‐TBB resin to collagen‐depleted dentin
Authors: Soeno Kohyoh , Suzuki Shiro , Taira Yohsuke , Atsuta Mitsuru
Published: March 2005

It has been reported that the tensile bond strength between the 4‐META/MMA‐TBB resin and dentin pretreated with 10% citric/3% ferric chloride solution decreased after immersion in water for 2 years. The current study investigated the effect of an experimental dentin conditioner on the bonding of 4‐META/MMA‐TBB resin to dentin after thermocycling. The experimental conditioner was an aqueous solution of 10% ascorbic acid and 5% ferric chloride (Exp). Human teeth were prepared to expose flat dentin surfaces. These were treated sequentially with 40% phosphoric acid, 10% sodium hypochlorite, and the experimental conditioner. A commercially available dentin conditioner, an aqueous solution of 10% citric/3% ferric chloride (10–3) was used for a control group. Stainless steel rods were bonded to the pretreated dentin surfaces with the use of the 4‐META/MMA‐TBB resin. Tensile bond strengths were determined after 0, 5,000, 10,000, 20,000 themocycles. All data were analyzed by ANOVA, and differences among groups were analyzed by Duncan's new multiple range test (n = 10, p < 0.05). The experimental group showed no significant decrease in bond strength through 20,000 thermocycles, while the control group exhibited significant decrease after 10,000 thermocycles. Mean bond strength of the experimental groups were significantly higher than those of the control group at both 10,000 and 20,000 thermocycles. A hybrid layer could not be identified in SEM micrographs of the experimental groups. 10–3‐conditioned specimen SEMs displayed crack formation between the adhesive resin and a hybrid layer. The experimental dentin pretreatment improved the bond strength of a 4‐META/MMA‐TBB resin to human dentin compared to 10–3 treatment after thermocycling. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 73B: 104–108, 2005
New parallel software (P_Anhar) for anharmonic vibrational calculations: Application to (CH3Li)2
Authors: Gohaud Neil , Begue Didier , Darrigan Clovis , Pouchan Claude
Published: March 2005

We present the development of a new parallel computer code (P_Anhar_v1.0) to calculate the vibrational spectrum of medium size molecules using a variational algorithm. The method is applied to the determination of a complete quartic anharmonic force field (B3LYP/cc‐pVTZ) for methyllithium, leading to a new interpretation of experimental data. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 743–754, 2005
Prognostic significance of circumferential margin involvement in rectal adenocarcinoma treated with preoperative chemoradiotherapy and low anterior resection
Authors: Luna‐Pérez Pedro , Bustos‐Cholico EfraÍn , Alvarado Isabel , Maffuz Antonio , Rodríguez‐Ramírez Saúl , Gutiérrez de la Barrera Marcos , Labastida Sonia
Published: March 2005

Introduction

Histologic examination of circumferential margins is an important predictor of local and distant relapse in non‐radiated rectal cancer. However, for patients who received preoperative chemoradiotherapy this role has not yet been addressed.

Methods

From January 1995 to December 1997, 61 patients with rectal adenocarcinoma located between 0 and 10 cm from anal verge with invasion into perirectal fat assessed by rectal ultrasound were included. All patients received 45 Gy + bolus infusion of 5‐FU (450 mg/m2/days 1–5, 28–33 of RT); 4–6 weeks later, surgery was performed. Circumferential margin was assessed (<2 mm was considered as positive). Five‐year survival was calculated by Kaplan–Meier method and comparison of groups with log‐rank test. Multivariate Cox regression analysis was performed to find risk factors affecting local control and survival.

Results

There were 35 males and 26 females, mean age 60.3 years. Twelve patients (19.7%) had circumferential margin involvement. Median follow‐up was 44 months. Overall local recurrence was observed in 6 of 61 patients (9.8%); in patients without circumferential margin involvement this was 8%, whereas it was 16% in those with circumferential margin involvement (P = 0.33). Distant recurrence was observed in 22% of patients without circumferential margin involvement; conversely, it was 58.3% in those with involvement (P = 0.02). Five‐year survival of patients without circumferential resection involvement margin was 81%, while it was 42% in patients with circumferential involvement (P = 0.006).

Conclusions

In patients with rectal cancer treated by preoperative chemoradiation plus total mesorectal excision (TME) and sphincter saving surgery, circumferential margin involvement is associated with high incidence of distant recurrence and cancer‐related death. J. Surg. Oncol. 2005;90:20–25. © 2005 Wiley‐Liss, Inc.