ffirs.tex 6/4/2010 11: 58 Page i RARE EARTH COORDINATION CHEMISTRY Rare Earth Coordination Chemistry: Fundamentals and Applications Edited by Chunhui Huang © 2010 John Wiley & Sons (Asia) Pte Ltd ISBN: 978-0-470-82485-6 ffirs.tex 6/4/2010 11: 58 Page iii RARE EARTH COORDINATION CHEMISTRY FUNDAMENTALS AND APPLICATIONS Editor Chunhui Huang Peking University, China John Wiley & Sons (Asia) Pte Ltd ffirs.tex 6/4/2010 Copyright © 2010 11: 58 Page iv John Wiley & Sons (Asia) Pte Ltd, Clementi Loop, # 02-01, Singapore 129809 Visit our Home Page on www.wiley.com All Rights Reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as expressly permitted by law, without either the prior written permission of the Publisher, or authorization through payment of the appropriate photocopy fee to the Copyright Clearance Center Requests for permission should be addressed to the Publisher, John Wiley & Sons (Asia) Pte Ltd, Clementi Loop, #02-01, Singapore 129809, tel: 65-64632400, fax: 65-64646912, email: enquiry@wiley.com Designations used by companies to distinguish their products are often claimed as trademarks All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners The Publisher is not associated with any product or vendor mentioned in this book All trademarks referred to in the text of this publication are the property of their respective owners This publication is designed to provide accurate and authoritative information in regard to the subject matter covered It is sold on the understanding that the Publisher is not engaged in rendering professional services If professional advice or other expert assistance is required, the services of a competent professional should be sought Other Wiley Editorial Offices John Wiley & Sons, Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK John Wiley & Sons Inc., 111 River Street, Hoboken, NJ 07030, USA Jossey-Bass, 989 Market Street, San Francisco, CA 94103-1741, USA Wiley-VCH Verlag GmbH, Boschstrasse 12, D-69469 Weinheim, Germany John Wiley & Sons Australia Ltd, 42 McDougall Street, Milton, Queensland 4064, Australia John Wiley & Sons Canada Ltd, 5353 Dundas Street West, Suite 400, Toronto, ONT, M9B 6H8, Canada Wiley also publishes its books in a variety of electronic formats Some content that appears in print may not be available in electronic books Library of Congress Cataloging-in-Publication Data Rare earth coordination chemistry: fundamentals and applications / [edited by] Chunhui Huang p cm Includes bibliographical references and index ISBN 978-0-470-82485-6 (cloth) Rare earths Rare earth metal compounds Coordination compounds I Huang, Chunhui, 1933-QD172.R2R235 2010 546’.41—dc22 2010000191 ISBN 978-0-470-82485-6 (HB) Typeset in 10/12pt Times by MPS Limited, A Macmillan Company Printed and bound in Singapore by Markono Print Media Pte Ltd, Singapore This book is printed on acid-free paper responsibly manufactured from sustainable forestry in which at least two trees are planted for each one used for paper production ftoc.tex 6/4/2010 11: 59 Page v Contents Author Biographies xiii Foreword xxi Preface Introduction Chunhui Huang and Zuqiang Bian 1.1 Electronic Configuration of Lanthanide Atoms in the Ground State 1.2 Lanthanide Contraction 1.3 Specificity of the Photophysical Properties of Rare Earth Compounds 1.3.1 Spectral Terms 1.3.2 Selection Rules for Atomic Spectra 1.3.3 Lifetime 1.3.4 Absorption Spectra 1.3.5 The Emission Spectra of Rare Earth Compounds 1.4 Specificities of Rare Earth Coordination Chemistry 1.4.1 Valence State of Rare Earth Elements 1.4.2 Chemical Bonding of Rare Earth Elements 1.4.3 Coordination Numbers of Rare Earth Complexes 1.4.4 Tetrad Effect of Lanthanide Elements – Changing Gradation Rules in Lanthanide Coordination Chemistry 1.5 Coordination Chemistry of Inorganic Compounds 1.5.1 Rare Earth Hydroxides 1.5.2 Rare Earth Halide and Perchlorate Compounds 1.5.3 Rare Earth Cyanide and Thiocyanate Compounds 1.5.4 Rare Earth Carbonate Compounds 1.5.5 Rare Earth Oxalate Compounds 1.5.6 Rare Earth Nitrate Compounds 1.5.7 Rare Earth Phosphate Compounds 1.5.8 Rare Earth Sulfate Compounds 1.5.9 Rare Earth Borate Compounds 1.6 Outlook Acknowledgments References xxiii 1 10 11 13 14 15 15 21 25 25 26 27 28 30 31 32 34 36 36 38 38 β-Diketonate Lanthanide Complexes Kezhi Wang 41 2.1 Introduction 2.2 Types of β-Diketones Used for Lanthanide Complexes 41 42 ftoc.tex 6/4/2010 11: 59 Page vi vi Contents 2.2.1 Mono(β-Diketone) Ligands 2.2.2 Bis(β-Diketones) Ligands 2.2.3 Dendritic β-Diketones Ligands 2.3 β-Diketonate Lanthanide Complexes 2.3.1 Mononuclear Lanthanide Complexes with β-Diketones 2.3.2 Polynuclear β-Diketonate Lanthanide Complexes 2.4 Summary and Outlook Acknowledgments References 42 44 44 47 47 71 83 85 85 Rare Earth Complexes with Carboxylic Acids, Polyaminopolycarboxylic Acids, and Amino Acids Ruiyao Wang and Zhiping Zheng 91 3.1 Introduction 3.2 Rare Earth Complexes with Carboxylic Acids 3.2.1 Preparation of Rare Earth Complexes with Carboxylic Acids 3.2.2 Structural Chemistry of Rare Earth Complexes with Carboxylic Acids 3.2.3 Solution Chemistry of Rare Earth Complexes with Carboxylic Acids 3.3 Rare Earth Complexes with Polyaminopolycarboxylic Acids 3.3.1 Preparation of Rare Earth Complexes with Polyaminopolycarboxylic Acids 3.3.2 Structural Chemistry of Rare Earth Complexes with Polyaminopolycarboxylic Acids 3.3.3 Solution Chemistry of Rare Earth Complexes with Polyaminopolycarboxylic Acids 3.4 Rare Earth Complexes with Amino Acids 3.4.1 Preparation of Rare Earth Complexes with Amino Acids 3.4.2 Structural Chemistry of Rare Earth Complexes with Amino Acids 3.4.3 Solution Chemistry of Rare Earth Complexes with Amino Acids 3.5 Summary and Outlook References 91 92 92 94 114 115 116 116 120 122 122 122 127 129 130 N-Based Rare Earth Complexes Xiaomei Zhang and Jianzhuang Jiang 137 4.1 Introduction 4.2 Rare Earth Complexes with Amide Type Ligands 4.2.1 Rare Earth Complexes with Aliphatic Amide Type Ligands 4.2.2 Rare Earth Complexes with Silyl Amide Type Ligands 4.3 Rare Earth Complexes with N-Heterocyclic Type Ligands 4.3.1 Rare Earth Complexes with Pyridine Type Ligands 4.3.2 Rare Earth Complexes with Imidazole Type Ligands 4.3.3 Rare Earth Complexes with Porphyrin Type Ligands 4.3.4 Rare Earth Complexes with Phthalocyanine Type Ligands 137 137 137 142 146 146 153 158 168 ftoc.tex 6/4/2010 11: 59 Page vii Contents 4.4 Rare Earth Complexes with Schiff Base Type Ligands 4.4.1 Rare Earth Complexes with Imine Type Ligands 4.4.2 Rare Earth Complexes with H2 Salen (30) Type Ligands 4.5 Outlook List of Abbreviations Acknowledgments References 173 174 180 185 185 186 186 Rare Earth Polyoxometalate Complexes Ying Lu and Enbo Wang 193 5.1 Synthesis 5.2 Types and Structure Features 5.2.1 RE-POM Clusters 5.2.2 Extending Structural RE–POMs Complexes 5.2.3 RE–Organo Cation POM Supermolecule Complexes 5.3 Applications 5.3.1 Luminescence 5.3.2 Magnetism 5.3.3 Catalysis 5.3.4 Medicine 5.4 Outlook References 193 194 194 208 217 218 218 221 221 223 223 223 Coordination Chemistry of Rare Earth Alkoxides, Aryloxides, and Hydroxides Zhiping Zheng and Ruiyao Wang 229 6.1 Introduction 6.2 Lanthanide Alkoxides, Aryloxides, and Macrocyclic Polyaryloxides 6.2.1 Preparative Methods 6.2.2 Structural Chemistry of Lanthanide Alkoxide Complexes 6.2.3 Applications of Lanthanide Alkoxides 6.3 Lanthanide Hydroxide Complexes 6.3.1 Rational Synthetic Methodologies for Lanthanide Hydroxide Complexes 6.3.2 Coordination Modes of Hydroxo Ligands and Key Lanthanide–Hydroxo Motifs 6.3.3 Properties and Possible Applications 6.4 Summary and Outlook Acknowledgments References vii 229 230 231 232 246 249 250 251 263 265 265 265 Rare Earth Metals Trapped Inside Fullerenes – Endohedral Metallofullerenes (EMFs) Xing Lu, Takeshi Akasaka, and Shigeru Nagase 273 7.1 Introduction 7.1.1 History of Discovery 273 273 ftoc.tex 6/4/2010 11: 59 Page viii viii Contents 7.1.2 What Can Be Encapsulated Inside Fullerenes? 7.2 Preparation and Purification of EMFs 7.2.1 Production Methods 7.2.2 Extraction of EMFs from Raw Soot 7.2.3 Separation and Purification of EMFs 7.3 General Structures and Properties of EMFs Encapsulating Rare Earth Metals 7.3.1 Geometrical Structures 7.3.2 Electronic Structures of EMFs: Intramolecular Charge Transfer 7.4 Chemistry of EMFs 7.4.1 Chemical Reactions of EMFs: An Overview 7.4.2 Positional Control of Encapsulated Metals by Exohedral Modifications 7.4.3 Chemical Properties of Cage Carbons Dictated by the Encapsulated Metals 7.4.4 Chemical Behaviors of EMFs Bearing Fused Pentagons 7.5 Applications of EMFs and Their Derivatives 7.5.1 Applications in Biology and Medicine 7.5.2 Applications in Material Science 7.6 Perspectives: Challenge and Chance Acknowledgments References 274 277 277 279 280 Organometallic Chemistry of the Lanthanide Metals Yingming Yao and Qi Shen 309 8.1 Introduction 8.2 Synthesis and Reactivity of Organolanthanide Complexes Containing Ln–C Bonds 8.2.1 Synthesis and Reactivity of Organolanthanide π-Complexes 8.2.2 Synthesis and Reactivity of Lanthanide Complexes Containing Ln–C σ-Bonds 8.2.3 Synthesis and Reactivity of Lanthanide N-Heterocyclic Carbene Complexes 8.2.4 Synthesis of Cationic Lanthanide Complexes 8.3 Synthesis and Reactivity of Lanthanide Hydride Complexes 8.3.1 Synthesis 8.3.2 Reactivity 8.4 Synthesis and Reactivity of Divalent Lanthanide Complexes 8.4.1 Synthesis of Classical Divalent Lanthanide Complexes 8.4.2 Synthesis of Non-classical Divalent Lanthanide Complexes 8.4.3 Reductive Reactivity 8.5 Organometallic Ce(IV) Complexes 8.6 Application in Homogeneous Catalysis 8.6.1 Organic Transformation 8.6.2 Polymerization 309 282 283 284 286 286 292 292 293 294 295 297 299 299 300 310 310 314 320 322 325 325 328 330 330 331 333 334 337 337 339 ftoc.tex 6/4/2010 11: 59 Page ix Contents 10 11 ix 8.7 Summary and Outlook References 345 346 Lanthanide Based Magnetic Molecular Materials Bingwu Wang, Shangda Jiang, Xiuteng Wang, and Song Gao 355 9.1 Introduction 9.2 Magnetic Coupling in Lanthanide Containing Molecular Materials 9.2.1 Magnetic Coupling Mechanism of Gd(III) Systems 9.2.2 Magnetic Coupling in Ln(III) Containing Systems with Orbital Moment Contribution 9.3 Magnetic Ordering in Lanthanide Based Molecular Materials 9.3.1 Lanthanide–Organic Radical Systems 9.3.2 4f–3d Heterometallic Systems 9.4 Magnetic Relaxation in Lanthanide Containing Molecular Materials 9.4.1 Introduction to Magnetic Relaxation 9.4.2 Magnetic Relaxation in Lanthanide Containing Complexes 9.5 Outlook Acknowledgments References 355 357 357 363 367 367 370 378 378 381 396 397 397 Gadolinium Complexes as MRI Contrast Agents for Diagnosis Wingtak Wong and Kannie Waiyan Chan 407 10.1 Clinical Magnetic Resonance Imaging (MRI) Contrast Agents 10.1.1 Development of Clinical Contrast Agents 10.1.2 Clinical Contrast Agents 10.2 Chemistry of Gadolinium Based Contrast Agents 10.2.1 Relaxivity 10.2.2 Biomolecular Interactions 10.2.3 Toxicity and Safety Issues 10.3 Contrast Enhanced MRI for Disease Diagnosis 10.3.1 Magnetic Resonance Angiography (MRA) 10.3.2 Liver Disease 10.3.3 Oncology 10.4 Outlook References 407 408 409 412 412 418 420 421 422 423 424 425 426 Electroluminescence Based on Lanthanide Complexes Zuqiang Bian and Chunhui Huang 435 11.1 Introduction 11.1.1 Operating Principles in OLEDs 11.1.2 History of OLEDs 11.1.3 Potential Advantages of Lanthanide Complexes Used in OLEDs 11.2 Lanthanide Complexes Used in OLEDs 11.2.1 Europium Complexes 435 436 438 440 441 442 ftoc.tex 6/4/2010 11: 59 Page x x 12 13 Contents 11.2.2 Terbium Complexes 11.2.3 Other Lanthanide Complexes 11.3 Outlook Acknowledgments References 455 464 468 468 468 Near-Infrared (NIR) Luminescence from Lanthanide(III) Complexes Zhongning Chen and Haibing Xu 473 12.1 Introduction 12.2 Organic Antenna Chromophores as Sensitizers 12.2.1 Acyclic Ligands as Antenna Chromophores 12.2.2 Macrocyclic Ligands as Antenna Chromophores 12.3 Metal–Organic Chromophores as Sensitizers 12.3.1 d-Block Chromophores 12.3.2 f-Block Chromophores 12.4 Outlook List of Abbreviations Acknowledgments References 473 475 476 492 500 500 516 517 518 519 519 Luminescent Rare Earth Complexes as Chemosensors and Bioimaging Probes Fuyou Li, Hong Yang, and He Hu 529 13.1 Introduction 13.2 Rare Earth Complexes as Luminescent Chemosensors 13.2.1 Basic Concept 13.2.2 Rare Earth Complexes as Luminescent pH Chemosensors 13.2.3 Rare Earth Complexes as Luminescent Chemosensors for Cations 13.2.4 Rare Earth Complexes as Luminescent Chemosensors for Anions 13.2.5 Rare Earth Complexes as Luminescent Chemosensors for Small Molecules 13.3 Bioimaging Based on Luminescent Rare Earth Complexes 13.3.1 Time-Resolved Luminescence Imaging 13.3.2 Types of Luminescent Rare Earth Complexes for Bioimaging 13.3.3 Luminescent Rare Earth Complexes with “Privileged’’ Cyclen Core Structures as Bioimaging Probes 13.3.4 Luminescent Rare Earth Complexes with Bis(benzimidazole) pyridine Tridentate Units as Bioimaging Probes 13.3.5 Hybrid Rare Earth Complexes as Luminescent Probes in Bioimaging 13.4 Rare Earth Luminescent Chemosensors as Bioimaging Probes 13.4.1 Rare Earth Luminescent Chemosensors as Bioimaging Probes of Zn2+ 529 531 531 532 534 537 540 542 542 543 544 549 552 552 553 c13.tex 3/4/2010 21: 14 Page 561 Luminescent Rare Earth Complexes as Chemosensors and Bioimaging Probes 561 Figure 13.38 TEM images of (A) hydrophobic UCNP and (B) UCNP@ SiO2 (FITC)-NH2 nanocomposites HO2C HO2C HO2C ff Rudlo n ux-vo Lemie reagent OOOOOOO O O OO O OO O OO OO OO OOO HO2C HO2C (a) CO2H OO OOO OOO O O O O O O O O OO OO OOOO O CO2H CO2H CO2H CO2H O O n n O O On OHO OHO O HO O O O Cl O O CO3H (b) CO2H CO2H O OOOO OO OO O O O O O O O O OO OO OOOO n HO O mPEG-OH O O O O O O O O O O n O HO O HO OOOO OO OO O O O O O O O O OO OO OOOO OH n O O O OH O OH O n O O O n O O O n O O O n OH OHO OHO O nO O nO Figure 13.39 Surface ligand oxidation strategy for synthesis of functionalized oleic acid-capped UCNPs (a) Direct oxidization with the Lemieux-von Rudloff reagent and (b) epoxidation and further coupling with mPEG-OH hydrophobic UCNPs into water-soluble and surface-functionalized ones One of the strategies is to directly oxidize oleic acid ligands with the Lemieux-von Rudloff reagent into azelaic acids [HOOC(CH2 )7 COOH], which results in the generation of free carboxylic acid groups on the surface (Figure 13.39a) [125] The second strategy is based on epoxidation of the surface oleic acid molecules and further coupling with polyethylene glycol monomethyl ether (mPEG-OH), as shown in Figure 13.39b [126] However, such two-step conversion strategies for upconversion nanophosphors have some intrinsic limitations, such as complicated preparation and post-treatment procedures Therefore, one-pot synthesis of water-soluble and surface-functionalized UCNPs has been attracting more attention The groups working with Zhang [127] and Liu [128] employed c13.tex 3/4/2010 21: 14 Page 562 562 Rare Earth Coordination Chemistry polyethyleneimine (PEI) to synthesize water-soluble nanoparticles and to control crystal growth Very recently, we reported a new hydrothermal microemulsion synthesis strategy assisted by bi-functional ligand 6-aminohexanoic acid to synthesize amine-functionalized UCNPs [129] When the microemulsion containing lanthanide complexes of 6-aminohexanoic acid was mixed with another microemulsion containing aqueous NaF solution, nanoparticles were formed By further hydrothermal treatment at 180◦ C for an appropriate period of time, the reverse micelles could be broken, and larger UCNPs could be prepared The amine content of the UCNPs was determined to be about 9.5 × 10−5 mol g−1 , confirming the occurrence of amine surface groups on the UCNPs In this system, 6-aminohexanoic acid plays an important role in providing UCNPs with a desirable amine surface 13.6.4 Rare Earth Upconversion Luminescence Nanophosphors as Bioimaging Nanoprobes The application of UCNPs in microscopic imaging demands the development of a novel microscopy technique, namely upconversion luminescence (UCL) microscopy Recently, we demonstrated that rare earth nanophosphors exhibited unique UCL imaging modality, which was significantly distinct from those of single-photon and two-photon fluorescence imaging Interestingly, UCL of UCNPs was observed along the path of the laser beam This might be attributed to the unique upconversion mechanism of UCNPs Furthermore, to eliminate the hindrance of out-of-focus UCL, a confocal pinhole was introduced Finally, a new method of laser scanning upconversion luminescence microscopy (LSUCLM, Figure 13.40) was developed for the three-dimensional visualization of biological samples [130] Further practical applications of upconversion luminescence nanophosphors (UCNPs) in bioimaging has attracted more attention [129–132] For example, on the basis of the folate receptor (FR) overexpression in some tumor cells (such as HeLa cells) and the high-affinity between FR and folic acid (FA), we fabricated FA-conjugated UNCPs for targeted UCL imaging of FR-overexpressing HeLa tumors in vivo [129] To evaluate the FR target recognition of FA conjugated nanophosphors (UCNPs-FA), HeLa (FR-positive) and MCF-7 (FR-negative) cells were incubated in a serum-free medium containing UCNPs-FA (67 µg mL−1 ) at 37◦ C for h For comparison, HeLa cells were also incubated in the presence of non-conjugated Specimen z Scanning stage Objective lens Reverse excitation dichroic mirror Confocal Filter Detector pinhole Galvanometer mirrors CW 980 nm Figure 13.40 Schematic layout of a LSUCLM system set-up The excitation laser beam path is shown with a dotted line, and the emission pathway is shown in a solid line c13.tex 3/4/2010 21: 14 Page 563 Luminescent Rare Earth Complexes as Chemosensors and Bioimaging Probes Green channel Red channel Brightfield 563 Merge A 20um 20um 20um 20um 20um 20um 20um 20um 20um 20um 20um 20um B C Figure 13.41 Laser scanning UCL images of living cells (A) HeLa (FR-positive) cells incubated with UCNPs-FA; (B) MCF-7 (FR-negative) cells incubated with UCNPs-FA; (C) HeLa cells incubated with UCNPs-NH2 Green and red channel images were collected at 500–560 and 600–700 nm, respectively The merging of green channel and brightfield images is also shown [129] (Reproduced from Biomaterials, 30, L.Q Xiong et al., “Synthesis, characterization, and in vivo targeted imaging of amine-functionalized rare-earth up-converting nanophosphors,’’ 5592–5600, 2009, with permission from Elsevier.) nanoparticles (67 µg mL−1 UCNPs-NH2 ) under otherwise identical conditions As displayed in Figure 13.41A, UCNPs-FA–treated HeLa cells showed intense intracellular UCL signals at 500–560 nm (green channel) and 600–700 nm (red channel) under CW 980 nm excitation, indicating the high specific interaction between FA on the UCNPs-FA nanoparticles and FR on the HeLa cells In contrast, both UCNPs-FA–treated MCF-7 cells (Figure 13.41B) and UCNPs-NH2 −treated HeLa cells (Figure 13.41C) display weak luminescence in the green and red channels, suggesting low-rate non-specific binding of these nanoparticles to the cells These results establish that UCNPs-FA could be used for targeting and imaging HeLa cells with overexpressed FR Further quantification of the UCL signal of UCNPs-FA–treated HeLa cells across the line reveals extremely high UCL intensity (counts > 4095, region-1 and region-3) and no background fluorescence (counts around 0, region-2) as shown in Figure 13.42a This feature of perfect signal-to-noise ratio in UCL imaging cannot be obtained in single-photon or two-photon fluorescent imaging Moreover, as shown in Figure 13.42b, the data in the time-sequential scanning reveals no obvious change in the UCL intensity of the cells under continuous illumination (415 s) with a high power CW 980 nm laser (approximately 4.6 × 109 mW cm−2 in the focal plane) This fact reveals that UCNPs are highly resistant to photobleaching compared with conventional luminescent labels [129] c13.tex 3/4/2010 21: 14 Page 564 564 Rare Earth Coordination Chemistry (a) (b) 1.0 Normalized PL intensity 4000 Intensity 3000 1.0 5um 0.5 0.0 0.8 0.6 0.4 0.2 0.0 10 15 20 Position /µm 25 30 100 200 Time /s 300 400 Figure 13.42 (a) UCL intensity along the line shown in UCL image (inset) of UCNPs-FA-treated HeLa cell and (b) the normalized UCL intensity as a function of illumination time [129] (Reproduced from Biomaterials, 30, L.Q Xiong et al., “Synthesis, characterization, and in vivo targeted imaging of amine-functionalized rare-earth up-converting nanophosphors,’’ 5592–5600, 2009, with permission from Elsevier.) Brightfield Merge 95.00 121.25 A 147.50 173.75 199.99 95.00 116.56 B 138.13 159.69 181.25 Figure 13.43 In vivo upconversion luminescence imaging of subcutaneous HeLa tumor-bearing athymic nude mice (right hind leg) after intravenous injection of (A) UCNPs-NH2 or (B) UCNPs-FA All images were acquired under the same instrumental conditions (power density approximately 120 mW cm−2 on the surface of the mouse) [129] (Reproduced from Biomaterials, 30, L.Q Xiong et al., “Synthesis, characterization, and in vivo targeted imaging of amine-functionalized rare-earth up-converting nanophosphors,’’ 5592–5600, 2009, with permission from Elsevier.) Furthermore, the ability of folic acid conjugated nanophosphors (UCNPs-FA) to target a folic receptor (FR) in vivo was evaluated by UCL imaging of mice bearing HeLa (FRpositive) tumors As shown in Figure 13.43B, a significantly strong UCL signal was measured in the tumor after intravenous injection of UCNPs-FA after 24 h, whereas weak UCL was c13.tex 3/4/2010 21: 14 Page 565 Luminescent Rare Earth Complexes as Chemosensors and Bioimaging Probes 565 observed in the tumor of the UCNPs-NH2 -treated mouse (Figure 13.43A) Furthermore, the UCL signal from the tumor was inhibited in the presence of a blocking dose of FA (10 mg kg−1 ) The successful tumor imaging described above illustrates the specific in vivo FR-targeting of UCNPs-FA [129] 13.7 Outlook Notwithstanding the significant progress in the lanthanide complexes and nanophosphors as luminescent systems for sensing and bioimaging, there appears to exist tremendous opportunities for further development Methods for designing and synthesizing of adequate Ln(III) receptors are essentially at hand and will not constitute a handicap any longer in the future A heavy demand for targeted diagnostic imaging and for monitoring of reactions taking place in living cells will pose the key challenge for future luminescent responsive lanthanide-based systems for bioimaging in vivo and mainly in cellulo A combination of polymer techniques and biochemical reactions may be capable of producing new classes of efficient luminescent sensors Similarly, nanoparticle labels are presently attracting attention for the same reason Further efforts are starting to emerge to improve several technical aspects, including instrumentation and excitation mode With respect to the latter, multi-photon absorption is probably a valid option Considering the advantage of upconversion luminescence of lanthanide-based nanophosphors, one may predict that an ideal luminescent diagnostic assay could feature such a probe with a continuous wave excitation at 980 nm, a wavelength for which cheap laser diodes are available Further research on upconversion luminescence nanophosphors (UCNPs) will involve: (i) synthesis of monodisperse UCNPs with small size (