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Progress in Chemistry 2013, No.04 Previous issue Next issue

In this issue:

Future Bioinorganic Chemistry——Editor’s Viewpoints
2013, 25 (04): 431-434 |
Published: 24 April 2013
Abstract
Paradigm Shift in Bioinorganic Chemistry: Enzymatic Polycondensation Reaction of Silica in Siliceous Sponges
Wang Xiaohong*, Gan Lu, Heinz C. Schröder, Werner E.G. M黮ler*
2013, 25 (04): 435-445 | DOI: 10.7536/PC120801
Published: 24 April 2013
Abstract

The discovery of silicatein caused a paradigm shift, since it is the first enzyme which catalyzes the synthesis of a polymeric inorganic molecule from inorganic monomers. Molecular biological, biochemical and cell-biological data showed that the synthesis of siliceous spicules in both demosponges and hexactinellids is enzymatically driven via silicatein. This enzyme exists both intra-spicularly and in the extra-spicular space. It catalyzes the formation of bio-silica constituting the silica lamellae that are formed during the appositional (layer-by-layer) growth of the spicules. The extent of (bio-silica forming) activity of silicatein from the demosponge Suberites domuncula measured in vitro reflects the amount of bio-silica required for the formation of spicules in vivo. It is furthermore summarized that during growth and maturation of the spicules in demosponges a bio-fusion process occurs that results in an intra-spicular sintering of the silica lamellae to form compact silica rods. Finally we report that for the formation of the strong and stiff bio-silica skeleton of sponges a hardening process is required that is (presumably) driven by cell-membrane bound aquaporin channels which allow the removal of water, which is released during the bio-silica polycondensation reaction.

Progress in Bioinformatics Studies on Essential Metals
Li Gaopeng, Zhang Yan*
2013, 25 (04): 446-456 | DOI: 10.7536/PC121131
Published: 24 April 2013
Abstract

Metals are utilized through the three domains of life. Except for potassium, calcium, sodium and magnesium, all essential metals are trace elements. They play important roles in a variety of biological processes, but are needed in very small quantities. Previously, much effort has been focused on experimental studies of metal utilization pathways and metalloproteins. However, with the accumulation of large amount of data from genomics and proteomics studies, it becomes necessary and possible for computational and systematic analyses of the metallomes (or metalloproteomes) to be carried on, which would provide new insights into metal utilization, metabolization and biological functions. In this review, we introduce recent advances in bioinformatics studies on several metals, such as copper, molybdenum, nickel, cobalt, zinc, iron and the metalloid selenium. Furthermore, we also discuss the major techniques and recent advances of high-throughput ionomics studies. We hope that this review may provide a foundation for investigating the fundamental questions and future directions of metal research.

Contents
1 Introduction
2 Copper
3 Molybdenum
4 Nickel and cobalt
5 Zinc
6 Iron
7 Selenium
8 Ionomics
9 Conclusions and outlook

Metal-Based Particles in Biological Media: Impact and Challenge
Wang Kui*, Yang Xiaogai*
2013, 25 (04): 457-468 | DOI: 10.7536/PC130107
Published: 24 April 2013
Abstract

Spontaneously formed metal-based bioparticles, such as those formed in situ and intrinsic particles transformed ex situ, as well as in vivo modified and transformed extrinsic particles, are often present in the biogical media including body fluids, tissues and biointerfaces. The size of these particles are between nano- and micro- meters. Most of them are involved in the physiological, pathological and toxicological processes. Up to now, however, there is a lack of research on the relationship between the biological effects and the formation, structure and properties of these particles. The present article lists some facts and preliminary understanding about these metal-based bioparticles. Some research areas to be investigated are also proposed. The findings in these areas may provide the insight into the studies on the environment, health, disease control and so on.

Contents
1 Introduction
2 Calcium-based bioparticles under physiological conditions
2.1 Calcium phosphate nanoparticles in bone formation and remodeling
2.2 Calcium phosphate nanoparticles in tooth formation
2.3 Calcium-based nanoparticles under physiological conditions
3 Metal-based bioparticles formed in the pathological process
3.1 Nephronic systemic fibrosis and Gd-containing particles
3.2 Renal failure and deposition of metal-based bioparticles
3.3 Vascular calcification and calcific uremic arteriolopathy
3.4 Calcium-based bioparticles in the stone formation of urinary tract
3.5 Basic calcium phosphate in the synovial fluid
3.6 From nanobacteria to calcifying nanoparticle
4 In vivo modificaton of extrinsic nanoparticles and their biological effects
4.1 In vivo modificaton of extrinsic nanoparticles
4.2 Generality and specificity of nanoparticles-induced toxicity
4.3 The dual biological effects of cerium oxide nanoparticles
5 In vitro formation of metal-based bioparticles
5.1 Formation of metal-based bioparticles in the simulated biological fluid
5.2 Cell-involved formation, transport and transformation of bioparticles
5.3 Influence of metal-based bioparticles on gene transfection efficiency
5.4 Alum as a vaccine adjuvant
6 Summary and perspective

The Study of Biological Inorganic Chemistry Problemsin Translational Medicine
Zhang Jinchao*, Hu Yi*, Yu Siwang, Gao Yuxi, Zhang Haisong
2013, 25 (04): 469-478 | DOI: 10.7536/PC121136
Published: 24 April 2013
Abstract

Translational medicine is an emerging concept in the fields of biomedical research and healthcare since twenty-first century. It is a two-way process from the basic research to clinical application with direct feedbacks in between. It is not a new subject, but emphasizes a concept. It stems from an unmet need in clinical medicine. At present, translational medical research is mainly involved in the following areas: cancer, cardiovascular diseases, metabolic disorders, psychiatric disorders, diseases of the locomotor system, genetic diseases, organ transplantation, tissue engineering, disease diagnosis, drug research and development, personalized therapy, stem cell research, animal model studies and immunology etc. This article reviews the bioinorganic chemistry problems involved in the disease diagnosis, tissue engineering, individual therapy, drug research and development and disease mechanisms. Finally, the development of this new area and important issues to be studied are outlooked.Contents
1 The bioinorganic chemistry problems in disease diagnosis
1.1 New diagnosis methods
1.2 Imaging technology
2 The bioinorganic chemistry problems in tissue engineering
3 The bioinorganic chemistry problems in individual therapy
4 The bioinorganic chemistry problems in drug research and development
4.1 From single-target drug design to systematic intervention
4.2 Emerging nanomedicine
5 The bioinorganic chemistry problems in molecular mechanisms of diseases
5.1 The relationship between metal homeostasis and neurodegenerative diseases
5.2 The relationship between oxygen (nitrogen) homeostasis and neurodegenerative diseases
6 Outlook

Selenoprotein M and Its Effects on Diseases
Chen Ping, Jiang Liang, Liu Qiong*, Yang Silin, Song Yun, Ni Jiazuan
2013, 25 (04): 479-487 | DOI: 10.7536/PC120631
Published: 24 April 2013
Abstract

Selenoprotein M (SelM) was discovered in 2002 by bioinformatics analysis. SelM is located in the endoplasmic reticulum, containing a common redox motif cysteine-X-X-selenocysteine. SelM attracts great attention due to its high expression in brain and its potential roles in antioxidative defense, neuroprotective function and cytosolic calcium regulation. This paper reviews recent research progress in SelM, especially its biological function and its relation with diseases, together with the author's work on SelM. The prospect of SelM research is also discussed in this paper.

Contents
1 Introduction
2 The primary structure of SelM and its distribution
3 The spatial structure of SelM
4 The biological function of SelM
4.1 Antioxidative function
4.2 Interaction with metal ions
4.3 Calcium regulation
5 Relation between SelM and diseases
5.1 SelM and AD
5.2 SelM and reproduction and development
5.3 SelM and cancer prevention
6 Perspectives

Selenoproteins and Diabetes——Dual Effect of Selenium
Zhou Jun, Bai Zhaoshuai, Xu Huibi, Huang Kaixun*
2013, 25 (04): 488-494 | DOI: 10.7536/PC121052
Published: 24 April 2013
Abstract

Diabetes is one of the most common diseases affecting human health in the world, and insulin resistance has been recognized as an important contributor to the generation of type 2 diabetes, accounting for 90% of diabetes. Selenium, an essential trace element in human nutrition, is closely related to human health through incorporation into selenoproteins which have a wide range of important biological functions. In recent years the studies focusing on the relationship between selenium and diabetes have attracted much attention. Earlier studies showed that selenium has insulin-like effects, and thus may be promising in the prevention and treatment of diabetes. However, recent human trials and animal studies provided evidence that selenium plays a dual role in the initiation and development of diabetes, and long-term selenium supplementation unexpectedly increases the risk of insulin resistance and type 2 diabetes. Furthermore, the dual effect of selenium in the initiation and development of diabetes might be associated with a variety of selenoproteins, such as glutathione peroxidase 1 (GPx1), selenoprotein S (SelS) and selenoprotein P (SelP). This review summarizes the dual effect of selenium in diabetes, and the roles of selenoproteins in the initiation and development of diabetes. The prospect of this field is addressed as well.

Contents
1 Introduction
2 The insulin-like effects of selenium and the underlying mechanisms
3 Critical role of selenium in initiation and development of diabetes
4 Role of selenoproteins in initiation and development of diabetes and the underlying mechanisms
5 Conclusion and outlook

Recent Progress of Copper and Nickel Chaperones
Yang Xinming, Xu Dechen, Cheng Tianfan, Xi Zhaoyong, Zhao Linhong, Liu Yangzhong*, Sun Hongzhe*
2013, 25 (04): 495-510 | DOI: 10.7536/PC121213
Published: 24 April 2013
Abstract

Maturation of copper- and nickel-containing enzymes relies on a battery of metallochaperones, which play an important role in the transport and trafficking of Cu or Ni, and assist the assembly of metallocenter in metalloenzymes. Significant progress on the structure and function of metallochaperones has been made in the past years, improving our understanding on the homeostasis of Cu/Ni in cells. Recent progress of Cu/Ni chaperones is summarized in this review. The blueprint of Cu import and homeostasis is briefly discussed followed by the structural and functional aspects of selected Cu chaperones, i.e. Atox1, Cox17 and CCS. Moreover, the putative relationships between Cu chaperones and drugs are discussed. The second part focuses on the maturation of hydrogenase and urease, in which a series of Ni chaperones interacts with each other to achieve the homeostasis of nickel. Selected structural complexes and in vivo functional study of the chaperones are emphasized, the “cross-talk” between the two maturation pathways is presented.

Contents
1 Introduction
2 Copper chaperones
2.1 Cu import and homeostasis
2.2 Atox1
2.3 Cox17
2.4 CCS
2.5 Copper chaperones in relation to drugs
3 Nickel chaperones
3.1 Ni importer, regulator and storage
3.2 Ni chaperones for the maturation of urease
3.3 Ni chaperones for the maturation of hydrogenase
3.4 Cross-talk between the maturation of urease and hydrogenase
4 Conclusion

Metals Homeostasis and Related Proteins in Alzheimer’s Disease
Lü Xiaoping, Tan Xiangshi*
2013, 25 (04): 511-519 | DOI: 10.7536/PC120955
Published: 24 April 2013
Abstract

Alzheimer’s disease (AD) is a kind of neurodegenerative diseases often found in old people. The characteristic pathological features of Alzheimer’s disease are senile plaques, neurofibrillary tangles, the loss of neurons,and granulovacuolar degeneration. Though the mechanism of Alzheimer’s disease is very complicated and not understood clearly, the metal homeostasis,which amyloid beta, amyloid precursor protein and metallothionein-3 participated in, is associated with the development of Alzheimer’s disease. The transitional metals, such as copper and zinc, play a key role in the physiologic function. Abnormally high levels of metals were found in the brain of Alzheimer’s disease patients compared with the healthy people. The aberrant of metal homeostasis may be one of the reasons that induce Alzheimer’s disease. The imbalance of metal homeostasis in the brain of Alzheimer’s disease leads to the aggregation of amyloid beta and the generation of reactive oxygen species. The copper can generate reactive oxygen species via Fenton type reaction, resulting in toxicity to the cells. Metallothionein-3, as a metal homeostasis regulator, can protect against the neuronal toxicity of Aβ by preventing copper-mediated Aβ aggregation, abolishing the production of reactive oxygen species(ROS). This review focuses on the AD research progress regarding the metal homeostasis regulation with some related proteins.

Contents
1 Introduction
2 Metals homeostasis in the brain and Alzheimer’s disease
2.1 Copper homeostasis and Alzheimer’s disease
2.2 Zinc homeostasis and Alzheimer’s disease
2.3 Iron homeostasis and Alzheimer’s disease
3 Amyloid beta and Alzheimer’s disease
4 Amyloid precursor protein and Alzheimer’s disease
5 Metallothionein-3 and Alzheimer’s disease
6 Outlook

Mediating Roles of Metal Ions in the Structures and Functions of Metalloproteins
Xu Caihong, Zhao Yaqin, Yang Binsheng*
2013, 25 (04): 520-529 | DOI: 10.7536/PC121007
Published: 24 April 2013
Abstract

Biometals play important roles in biological process by different chemical actions. The biomembranes enable different metals to acquire different distribution mode among compartments in a biological system.Metalloproteins or metal chaperones are required to maintain cellular metal ions homeostasis. In cells and intracellular organelles there are many proteins whose metal binding sites consist of more metal ions and are not equivalent in thermodynamics. The functions of metalloproteins are mediated by the binding of metal ions, such as that of concanavalin A, Cu/Zn superoxide dismutase, centrin, and zinc fingers protein. That the binding of metal ions to proteins are investigated is of great significance for bioinorganic chemists to understand the roles of metal ions in mediating the functional changes of metalloproteins.

Contents
1 Introduction
2 Concanavalin A
2.1 Structure
2.2 Functional changes mediated by the binding of metal ions
3 Cu/Zn superoxide dismutase
3.1 Structure
3.2 Biological functions
3.3 Functional changes mediated by the binding of metal ions
4 Centrin
4.1 Biological functions
4.2 Structure
4.3 Functional changes mediated by the binding of metal ions
5 Zinc fingers protein
5.1 Structures of zinc fingers
5.2 The binding of metal ions
5.3 Regulation of biological functions by zinc ion
6 Conclusion and outlook

Structural Basis of Human Serum Albumin and Its Complexes
Yang Feng, Liang Hong*
2013, 25 (04): 530-538 | DOI: 10.7536/PC121125
Published: 24 April 2013
Abstract

Human serum albumin is the most abundant protein in plasma and one of the major binders/carriers of fatty acid and drugs, plays an essential role in pharmacokinetics and delivery of drugs for it transports a wide variety of drugs to target organs and tissues. In the past forty years, the interaction between albumin and compounds is research hotspots both at home and abroad. Furthermore, human serum albumin has been extensively studied as drug carrier. Therefore, this paper first reviews the knowledge on structure of human serum albumin and its complexes, and then puts forward some future challenges on human serum albumin field.

Contents
1 Introduction
2 Structural basis of human serum albumin
2.1 Overall structure of human serum albumin
2.2 Sub-domain structure of human serum albumin
2.3 Cysteine-34 of human serum albumin
3 Structural basis of human serumalbumin-fatty acids
3.1 Binding site of fatty acids at human serum albumin
3.2 Influence of fatty acids on conformation of human serum albumin
4 Structural basis of human serum albumin-drug
4.1 Site Ⅰ
4.2 Site Ⅱ
5 Conclusions and outlook

Review
Recent Progress on Molecular Recognition and Modulation of Nucleic Acids Using Chiral Rare-Earth Complexes
Zhao Chuanqi, Qu Xiaogang*
2013, 25 (04): 539-544 | DOI: 10.7536/PC121055
Published: 24 April 2013
Abstract

There is great interest in design and synthesis of small molecules which selectively target specific genes to inhibit biological functions. Among these studies, chiral DNA recognition has been received much attention because more evidences have shown that conversions of the chirality and diverse conformations of DNA are involved in a series of important life events. In addition, chiral molecular recognition of DNA is important for rational drug design and developing structural probes of DNA conformation. Over the past few decades, considerable attention has focused on the design of DNA binding chiral agents, especially B-DNA, Z-DNA and G-quadruplex DNA binding agents. Rare-earth compounds, due to a unique 4fn electronic configuration, have been widely used as probes in luminescent resonance energy transfer for bioassays and as reagents for diagnosis in magnetic resonance imaging. As chemical nucleases, rare-earth complexes have also shown a high efficiency to hydrolyze DNA and RNA without redox chemistry. Recently, there is great interest in the design and synthesis of chiral rare-earth complexes which selectively target specific DNA. Excitedly, some interesting results have been reported. This review summarizes the current progress in chiral rare-earth complexes binding to nucleic acids and their chiral selectivity.

Contents
1 Introduction
2 Synthesis of rare-earth chiral compounds
3 Recognition of rare-earth chiral compounds to duplex DNA
4 Recognition of rare-earth chiral compounds to single strand DNA and quadruplex DNA
5 Perspective

DNA Topoisomerase Inhibitors
Du Kejie, Wang Yi, Liang Jiewen, Ji Liangnian, Chao Hui*
2013, 25 (04): 545-554 | DOI: 10.7536/PC120820
Published: 24 April 2013
Abstract

DNA topoisomerases (Topo) are ubiquitous enzymes in eukaryotic cell and prokaryotic cell. They are crucial for cellular genetic processes, such as replication, recombination, transcription, chromosome condensation, and the maintenance of genome stability by catalyzing the passage of individual DNA strands (topoisomerase Ⅰ) or double helices (topoisomerase Ⅱ) through one another. In accordance, topoisomerases are over expressed in cancer cell growth and thus are important cellular targets for anticancer drugs. The structures and biological functions of topoisomerases are discussed in this review. Moreover, some recent progresses of organic compounds and metal complexes as DNA topoisomerase inhibitors are discussed in detail.

Contents
1 Introduction
2 Structures and mechanisms of DNA topoisomerases
2.1 Structures of DNA topoisomerases
2.2 Mechanisms of DNA topoisomerases
3 Biological functions of DNA topoisomerases
3.1 Regulation of topological states of DNA
3.2 Role of DNA topoisomerases in recombination and repair
4 DNA topoisomerases inhibitors
4.1 Mechanisms of DNA topoisomerase inhibition
4.2 Organic compounds as DNA topoisomerase inhibitors
4.3 Metal complexes as DNA topoisomerase inhibitors
5 Perpective

Introduction of Metal Complex-Nucleic Acid Interactions into Cells
Yang Chanli, Dong Xiongwei, Jiang Nan, Zhang Dan, Liu Changlin*
2013, 25 (04): 555-562 | DOI: 10.7536/PC121056
Published: 24 April 2013
Abstract

The exploration on metal complex-nucleic acid interactions plays key roles not only in rational design of both new metal-based anticancer drugs and effective hydrolytic cleaving agents of nucleic acids, but also in development of specific recognition probes of nucleic acid structures. Currently, the metal complex-nucleic acid interactions are being introduced into cell biological studies. For example, the intracellular localization imaging methods of nuclear and mitochondrial DNAs are being developed based on the DNA binding of ruthenium(Ⅱ) complexes. The effects of metal complex binding to nucleic acids on intracellular signal transduction and epigenetic inheritance have attracted a good deal of attention. The metal complexes that may act as nonviral nucleic acid carriers are being designed on the basis of their ability to condense nucleic acids. We review the important advances in investigation on the intracellular metal complex-nucleic acid interactions by utilization of typical cases.

Contents
1 Introduction
2 Metal complexes used as localization imaging agents of nuclear and mitochondrial DNAs
3 Effects of nucleic acid-metal complex interactions on intracellular signal transduction
4 Nucleic acid-metal complex interactions and epigenetic inheritance
5 Metal complexes used as nonviral nucleic acid carriers
6 Outlook

Bioinspired Catalysis for New Energy Exploration and CO2 Photoreduction
Liu Lei, Liu Jingang*
2013, 25 (04): 563-576 | DOI: 10.7536/PC121048
Published: 24 April 2013
Abstract

Inspired by natural photosynthesis, artificial photosynthesis using solar energy and abundant natural resources, H2O and CO2, to produce renewable energy fuels has recently been received considerable attentions. This review focuses on recent developments in construction of artificial photosynthesis systems. Special attention has been paid to the various kinds of transition metal complexes as photocatalysts employed in water oxidation as well as in CO2 photo-reduction reactions, the semi-reactions of artificial photosynthesis. The performances of various photocatalytic systems together with their related photocatalytic reaction mechanisms have been summarized and compared. The challenges of current studies and prospects for future development in artificial photosynthesis have also been suggested.

Contents
1 Introduction
2 Principles of natural photosynthesis and constr-uction of artificial photosynthesis
3 Photocatalysts for water splitting
3.1 Proton reduction for H2 evolution
3.2 Water oxidation for O2 evolution
4 Photocatalytic conversion of CO2
4.1 Mononuclear photocatalysts
4.2 Supermolecular photocatalysts
5 Conclusion

Metalloenzyme Mimics with Non-Covalent Interactions
Wang Haibo, Zhao Meng, Ji Liangnian, Mao Zongwan*
2013, 25 (04): 577-588 | DOI: 10.7536/PC121054
Published: 24 April 2013
Abstract

Metalloenzyme efficiency and specificity originate from the cooperative roles between the metal-mediated catalysis at the first coordination sphere and the non-covalent interactions at the secondary coordination sphere. While the structures and functions of metal coordination sites have drawn wide researches, the elucidations of the non-covalent interactions have been less assessed. The enzymatic non-covalent interactions in terms of hydrogen bonding, electrostatic attraction, van der Waals force and hydrophobic interaction are produced from the amino acid residues in the secondary coordination sphere. The primary hurdle that hampers the elucidation of the amino acids in the secondary coordination sphere is their complicated intra- and intermolecular interaction networks that are exceptionally difficult to define. A practical approach to circumvent this challenge is to prepare metalloenzyme mimics that include non-covalent interactions. This approach not only opens an avenue to understand the synergism between the non-covalent interactions and the metal ions, but also contributes to the development of biomimetic catalysts applied in industry, pharmaceutics, biotechnology and even wider areas. To make an overview of the recent progresses in this field, this review discusses the representative mimics which are organized according to the interaction categories. The mimics exemplified here include the ones based on the simple multi-dentate ligands like bipyridine, terpyridine, cyclic amine and porphyrin, and the supramolecular ligands like the functionalized cyclodextrins and calixarenes. Prior to the discussions of mimics, the non-covalent interactions of native metalloenzymes are commented.

Contents
1 Introduction
2 Non-covalent interactions in native metalloenzyme
2.1 Hydrolase
2.2 Oxido-reductase
3 Metalloenzyme models involving non-covalent interactions
3.1 Hydrogen bonding
3.2 Electrostatic interaction
3.3 Hydrophobic sphere
4 Conclusion and outlook

Bio-Inspired Functional Integration by Self-Assembly and Mineralization of Polysaccharides
Wang Yun, Huang Haibo, Chu Guang, Xu Yan*
2013, 25 (04): 589-610 | DOI: 10.7536/PC121135
Published: 24 April 2013
Abstract

Bio-inspired materials strategy seeks inspiration from nature for their use as models in the organization of advanced materials with embedded structural hierarchy. Biominerals are highly sophisticated interfacial materials and have functions integrated by self-assembly and mineralization of biomacromolecules. Polysaccharides, representing approximately three quarters of natural biomass resources, have the richness of structure, chemistry and actuation properties. They play critical roles in the organization and functional integration of biominerals, typical examples including chitin in lobster cuticle and nacre shells. Such materials can provide environmentally compatible solutions to some of the modern technological problems. Representative biominerals including nacre shells, lobster cuticle and diatom frustules, and some pertinent bio-inspired materials with salient structural functions are reviewed. The self-assembly and actuation properties of selected polysaccharides such as cellulose and alginate, and their inspiration to the design of advanced materials are covered. The concept of cooperative assembly of inorganic-polysaccharides interfacial materials is introduced, and representative advancement in bio-inspired functional integration by self-assembly and mineralization of polysaccharides are highlighted. It is hoped that this article will encourage further scientific investigations and invite more insightful view as how bio-inspired functional integration can be best achieved by self-assembly and mineralization of polysaccharides.

Magnetic Iron Oxide Nanoparticle-Based Theranostic Nanomedicine
Qi Hui, Zhu Yanhong*, Xu Huibi, Yang Xiangliang
2013, 25 (04): 611-619 | DOI: 10.7536/PC121033
Published: 24 April 2013
Abstract

Theranostic nanomedicine is emerging as a promising therapeutic strategy. Magnetic iron oxide nanoparticle-based theranostic nanomedicine takes advantage of nanotechnology to load both nanoparticle and therapeutic agent into one nanoparticle. The resulting nanosystem is composed of three main components: an iron oxide nanoparticle core, coating, and multifunction moieties. These nanoparticles are expected to play a significant role in personalized medicine for their capability of diagnosis, visualizing drug delivering and monitoring therapeutic response in real-time. In this review, we summarize the synthesis, surface modification, multifunction and biomedicine application of magnetic iron oxide nanoparticle, especially focused on the part of surface modification and multifunction, which are associated with the multimodality and multifunctionality theranostics. At last, the challenges of the application of nanomedicine in personalized medicine are presented.

Contents
1 Introduction
2 Synthesis of MNPs
3 The compounds commonly used in the surface modification of MNPs
3.1 Polymers
3.2 Inorganic shells
3.3 Small organic molecules
4 Surface functionalization of MNPs
4.1 Targeting modification of MNPs
4.2 Multifunction of MNPs
5 Application of theranostic nanomedicine based on MNPs
6 Challenge of theranostic nanomedicine in clinic

Phosphoprotein/Phosphopeptide Enrichment and Analysis Based on Nanostructured Materials
Cheng Gong, Wang Zhigang, Liu Yanlin, Zhang Jilin*, Sun Dehui, Ni Jiazuan
2013, 25 (04): 620-632 | DOI: 10.7536/PC121029
Published: 24 April 2013
Abstract

Protein phosphorylation is one of the most ubiquitous post-translational modifications. Many low-abundance endogenous phosphoproteins and phosphopeptides in the body fluids or tissues are biomarkers with higher clinical sensitivity and specificity, which could provide valuable information for the detection of many diseases and elucidation of pathology. It is still a great challenge to detect the phosphoproteins and phosphopeptides from complex biological samples directly due to reversibility of protein phosphorylation and the extremely low concentrations of phosphoproteins. Nanostructured materials have attracted particular attentions in enrichment, separation, and purification of phosphoproteins/phosphopeptides due to their larger surface area, numerous affinity sites and unique structures. The research subject has become one of research hotspots in phosphoproteomics presently. Various multifunctional nanostructured materials such as core-shell particles with mesoporous affinity shell and magnetic core, hybrids of multiple components and composite affinity materials have been synthesized for selective enrichment and fast purification of phosphoproteins/phosphopeptides. In this review, we are focusing on recent advancements of nanostructured materials for phosphoprotein/phosphopeptide enrichment and purification prior to MS analysis. Definition, structure characteristic, unique physicochemical properties and potential in bio-separation of the nanostructured materials are first introduced. Subsequently, the related research background on phosphoproteomic studies in proteomics using mass spectrometric strategies in combination with phosphospecific enrichment techniques is briefly presented. After that, two types of affinity enrichment mechanisms to phosphoproteins/phosphopeptides are compactly discussed. Next, mesoporous, hybrid, and composite nanostructured materials for enrichment of phosphoproteins/phosphopeptides as well as application of multifunctional nanostructured materials in phosphoproteomics are summarized in detail. Finally, some unsolved problems and a brief perspective and outlook on phosphopeptide enrichment are proposed.

Contents
1 Introduction
2 Protein phosphorylation and enrichment detection of phosphoproteins/phosphopeptides
2.1 Protein phosphorylation
2.2 Enrichment detection of phosphoproteins/phosphopeptides
3 Mechanism of affinity enrichment of phosphoproteins/phosphopeptides
4 Mesoporous nanostructured materials for enrichment of phosphoproteins/phosphopeptides
4.1 Mesoporous SiO2 nanostructured materials with immobilized affinity material
4.2 Mesoporous nanostructured materials doped with affinity material
4.3 Mesoporous metal oxide nanostructured materials
5 Composite nanostructured materials for enrichment of phosphoproteins/phosphopeptides
5.1 Magnetic core-shell nanostructured materials
5.2 Mesoporous magnetic nanostructured materials
5.3 Hybrid composite nanostructured materials
6 Application of multifunctional nanostructured materials in phosphoproteomics
6.1 Multifunctional nanostructured materials for fast proteolysis and phosphopeptide enrichment
6.2 Multifunctional nanostructured materials for enrichment and identification of phosphopeptides
6.3 Multifunctional nanostructured materials for enrichment of various biomolecules
6.4 Nanostructured materials modified target plate for on-plate enrichment and analysis of phosphopeptides
7 Conclusions and outlook

Biomineralization: One Promising Bridge between Inorganic Chemistry and Biomedicine
Wang Ben, Tang Ruikang*
2013, 25 (04): 633-641 | DOI: 10.7536/PC121059
Published: 24 April 2013
Abstract

Biomineralization refers to the processes by which organisms form minerals. The control exerted by many organisms over mineral formation distinguishes these processes from abiotic mineralization. In living organisms, nanoscale building blocks combine into self-assembled biominerals under the control of an organic matrix. Biomineralization, especially mineralization of unicellular organisms, physiologic and pathological mineralization, plays a vital role in biology and materials research and could offer a variety of inspirations for biomaterials design and biomedical engineering. As the basic building blocks of biological hard tissues such as bone, dentin, and enamel, hydroxyapatite (HAP) nanoparticles play an important role in the construction of biominerals. As analogues of biological units, nano-HAP can be used as ideal biomaterials due to their nice biocompatibility and bone/enamel integration. The construction of nanostructured calcium phosphates is highlighted in bone/tooth hard tissue engineering. Inspired by unicellular organisms, single cell and virus were entrapped in a biomimetic mineral shell and were endowed with enhanced resistance abilities in the hostile environment. Several ongoing works and related proceedings in this fields are highlighted in this article. The perspective from biomineralization to biomedical research including bone and teeth repair, cellular (virus) shell engineering are illustrated. As the bridge of inorganic chemistry and biomedicine, biomineralization is the well of knowledge for hard tissue repair, the guiding principle for preventing disease of pathological mineralization, the inspiration for cell interfacial engineering, and need to be exploited adequately.

Contents
1 Introduction
1.1 The summary of biomineralization
1.2 Calcium phosphate
2 Biomedical engineering inspired by biomineralization
2.1 Bone and teeth repair
2.2 Cellular (virus) shell engineering
3 Conclusions and outlook

Nucleation, Growth, and Aggregation of Nanocrystallites in Urine of Calcium Oxalate Stone Patients as well as Kidney Stone Formation
Ouyang Jianming*, Zhang Guangna, Wang Fengxin, Li Junjun
2013, 25 (04): 642-649 | DOI: 10.7536/PC121129
Published: 24 April 2013
Abstract

The main constituents of kidney stones are inorganic crystals such as calcium oxalate (CaOxa). At present kidney stones can be diagnosed only after formation, which brings great suffering to patients. The formation of kidney stones related closely to the properties of urinary nanocrystallites. If kidney stone can be detected prior to its formation, it might be effectively prevented. In this paper, an review is given about the differences of urinary nanocrystallites between the patients of kidney stone and healthy controls, as well as the relationship with the formation of kidney stones. These differences comprise size and distribution, agglomeration, morphology, chemical composition, Zeta potential and stability of the microcrystals. The changes in these properties in CaOxa stone patients before and after taking potassium citrate are discussed. It is concluded that agglomeration of urinary nanocrystallites is a key factor leading to rapid growth of the crystallites and formation of urinary stones. Through the regulation of physical and chemical properties of nanocrystallites, the formation and recurrence of kidney stones are possibly inhibited.

Contents
1 Introduction
2 Differences of urine crystallites of kidney stone patients and controls
2.1 Size
2.2 Aggregation
2.3 Morphology
2.4 Chemical composition
2.5 Zeta potential
2.6 Stability
3 Agglomeration of urinary nanocrystallites promotes stone formation
4 Properties changes in urinary nanocrystallites in calcium oxalate stone patients before and after potassium citrate administration
5 Conclusions and outlook

Update of Metal-Based Drugs: Problems and Approaches for Solution
Huang Meiling, Wu Yaling, Zhao Pan, Yang Xiaoda*
2013, 25 (04): 650-660 | DOI: 10.7536/PC121051
Published: 24 April 2013
Abstract

From this century, great progresses have been made in the field of metal-based medicine and relevant fundamental researches. However, there are also major problems left to be solved. This review summarized the recent progresses and the bottlenecks of two important metal drugs, anti-cancer platinum/non-platinum drugs and anti-diabetic vanadium compounds. The following aspects are proposed for attentions in the future research: (1) Discover new molecular mechanism of metal drugs for rational design of metal drugs; (2) Control of metal toxicity based on molecular mechanism; (3) Rational metal drug design and metal drug delivery system based on nano materials, molecular complexes and drug transporters; (4) Synthetic biology of metal complexes.

Contents
1 Introduction
2 Anti-cancer compounds
2.1 Drug resistance of cisplatin
2.2 Rational drug design
2.3 Improve bioavailability through drug design and targeted delivery
2.4 Novel anti-cancer strategy: poisoning cell vs prisoning cell
3 Anti-diabetic vanadium compounds
3.1 Mechanisms of pharmacological actions and rational drug design
3.2 Toxicity of vanadium compounds
3.3 Pharmacokinetics of vanadium compounds
4 Conclusions and outlook