Metal Complexes: Environmental and Biomedical Applications

PREFACE

A century ago, Alfred Werner won the Nobel Prize in chemistry for proposing the octahedral configuration of transition metal complexes and developing the foundation for modern coordination chemistry. His revolutionary research work was of significant importance for the development of the chemistry of metal complexes, which has diminished the border between organic and inorganic chemistry because it is the chemistry of organic ligands and inorganic metal ions. Metal complexes are being utilized in many aspects of human life due to their interesting and unique properties. Today, we find a significant increasing interest in the design of metal complexes for different applications. Some of these are used in multifarious fields of biomedical, energy, and environmental protection and are keenly observed among scientific communities across the globe. Metal complexes play major roles in many subject areas, including biochemistry, therapeutics, diagnosis, catalysis, sensing, and energy conversion. The reason and motivation to propose this book are to design new research plans for graduate students with their basic understanding of coordination chemistry during their undergraduate study.

Chapter 1 discusses the general oxidation states of various metal ions and the introduction to coordination complexes, followed by a discussion on the use of coordination compounds, their syntheses, and their characterization., Chapter 2 discusses the metal complexes synthesized from Schiff bases and N-heterocyclic carbenes. In Chapter 3, the cage metal complexes and their applications are described. Chapters 4 and 5 describe the metal complexes that are used in therapeutics and diagnostics. The application of metal complexes in solar energy conversion is discussed in Chapter 6. Chapter 7 discusses the use of metal complexes in analytical chemistry, and Chapter 8 discusses the use of metal complexes as catalysts in a variety of organic reactions. Chapter 9 discusses the anti-bacterial and anti-fungal applications of metal complexes, and Chapter 10 discusses the metal complexes used as sensors.

This book is intended for undergraduate and graduate students, instructors at the graduate level teaching related coursework, and those working in the diverse fields of biochemistry, biology, organic, inorganic, and bio-inorganic chemistry sciences. The text can prove beneficial for researchers, investigators, and scientists whose works involve organic chemistry, analytical chemistry, and inorganic chemistry, as well as those who are working on radiopharmaceuticals. It can serve as a reference book for P.G. and Ph.D.-level research scholars. All academic research libraries will benefit from having a copy of the book as a reference manual as well.

The writer’s own teaching and research experience of over one decade has played a crucial role in designing and writing the book.

Suggestions for improvement of the contents are most welcome from the students and research fraternity, which can be incorporated in future editions.

Rojalin Sahu

KIIT, Deemed to be University

Bhubaneswar Odisha

India

Puspanjali Sahu

Bhadrak Autonomous College

Bhadrak, Odisha

India

Introduction to Metal Complexes: A Special Reference to Oxidation States

Rojalin Sahu, Puspanjali Sahu

Associate Proffessor KIIT, Deemed to be University Bhubaneswar

Abstract

There are 90 elements on the earth’s crust. Among these, 81 are life supporting and the remaining 9 are radioactive in nature. The human body consists of nearly 3% of metals. Transition metals having partially filled d-subshell can easily accept and donate electrons and hence achieve variable oxidation state. These variable oxidation states enable the modulation of variable redox systems, which are available in biological systems. They can also interact with a wide range of negatively charged compounds. The aforementioned properties of transition metals have sparked the creation of metal-based drug development that holds great promise for medicinal use. Metal-based drugs (metallodrugs) are now used in theranostics, i.e., therapy and diagnosis. Metal-based drugs like oxaliplatin, carboplatin, and cisplatin are being used in the treatment of cancer. Moreover, transition metal-based drugs are also used to treat cardiovascular diseases, inflammation, rheumatoid arthritis, ulcer, diabetes etc. In this chapter, various oxidation states of transition metals of different series of the periodic table are briefly discussed, along with their application in the field of medical science.

Keywords: Oxidation state, transition metal, biological activity, metallodrugs, medical application.

* Corresponding author Dr. Rojalin Sahu: Associate Proffessor KIIT, Deemed to be University Bhubaneswar; E-mail: ???

INTRODUCTION

In the biological system, metal ions have an essential role, such as in disease therapy and diagnosis, which is known as medicinal inorganic chemistry [1]. In the field of bioinorganic chemistry, metal ion-bound components or metal ions are introduced into the biological system for treating a wide range of diseases. Metal has the property of losing electrons easily to form cations that dissolve in biological fluids. Metals exhibit their biological activity in positively charged forms. Proteins and DNA are examples of biological substances that are rich in electrons, whereas metal ions lack electrons. The attractive force between these two opposite charges enables metal ions to interact and bind with biological moieties. A similar concept applies to the affinity of metal ions for other tiny ions and necessary components of life, such as oxygen. Metal plays a wide range of activities, like shuttling electrons and transporting oxygen to different parts of the body. An iron-containingprotein named hemoglobin binds with oxygen

molecules and transports them to tissues of the body. In a similar manner, the skeletal framework of the human body is made up of minerals that contain calcium. Metals like Mn, Fe, Zn, and Cu are integrated into catalytic proteins like metalloenzymes, facilitating the chemical reactions necessary for life [2]. In clinical applications, metal complexes are already being used, and further research is encouraged for novel drug development based on metals to be used as anticancer, radio-sensitizing, anti-diabetes, anti-HIV [3], antiparasitic, antiviral, antibacterial, and antibiotic agents. The unique benefit offered by transition metal complexes is their ability to bind with DNA. Transition metal sites are attractive components for nucleic acid reversible identification as they show perfect coordination stereochemistry. Additionally, they exhibit distinct photophysical and electrochemical characteristics, hence enhancing the functionality of the binding agents [4]. Ru and Pt ions, among others, are considered coordination sites for efficient anticancer agents [5-7]. There is a great need for the production of cost-effective first-row transition metal compounds as effective DNA binding agents having low cytotoxicity [8-10]. Therefore, the focus is generally on studies concerned with some biological application of easily available and cheaper transition metal coordination compounds of the first row, such as Co (II), Fe (II), Mn (II), Cr (III), V(II), and V(IV). These metal ions are also important for the intracellular biological environment of living things. Transition metal-based complexes are important for photochemistry, material production, biological systems, and catalysis. A range of magnetic, optical, and chemical properties are also displayed by them.

OXIDATION STATE CONCEPT

The oxidation state of a transition metal in a complex refers to the left charge after all the ligands are eliminated. Further, the electron bonding pair between the ligands and the central metal ion is exclusively assigned to the bonding partner having more electronegativity, generally ligands [11]. This explanation is more practical in the case of ionic bonding. During redox-active ligand involvement and covalent bonding, the identification of the formal oxidation state is quite complicated, and the assigned oxidation state essentially differs from the actual distribution of electronic charge between the ligand and the metal. Therefore, strongly electronegative ligands like oxygen and fluorine are considered, and those examples are avoided where metal bonding occurs and redox-active ligands are present [12]. It is to be confirmed that the partial computed charges derived from the population analysis should not be compared equally with the formal oxidation number unless the case is the most ionic system [13].

3D TRANSITION SERIES ELEMENTS

Chromium (Cr)

Chromium is the first metal in this series, possessing a wide range of oxidation states from -2 to +6. Several oxyfluorides and oxo complexes are known in oxidation state (VI) for the binary oxides of Cr (VI). Matrix separation of CrF6 is also reported in the literature [14-16]. DFT and quantum chemical calculation are evident in the octahedral geometry of CrF6 [17].

Manganese (Mn)

Seven is the highest attainable oxidation state by manganese and is shown by many oxyfluorides, permanganate ions, and binary oxides. MnF4 is the highest oxidation state of manganese known for fluorides [18, 19]. Fluro manganate complexes exist like (XeF5)2MnF6(Cr) with variable oxidation states [20]. There are experimental attempts and speculation for the preparation of manganese fluorides with higher oxidation states such as [MnF6]- or MnF5.

Iron (Fe)

Experimentally, Fe (VI) is the highest attainable oxidation state in the form of the ion [FeO4]²- and nitride. Here, the central metal ion is hexa-coordinated in the complex [21]. X-ray absorption and Mossbauer spectroscopy are used for the characterization of the latter complex. The octahedral structure with 157 pm bond length in FeN at the terminal position is also supported by DFT calculation [22]. Fe (VI) system in FeO4 is confirmed by the low-temperature matrix isolation-IR spectroscopy in addition to the quantum-chemical calculations [23-25]. A single stretching band is not seen in the FeO4 tetrahedral molecule. Moreover, the CCSD(T) and B3LYP calculations confirm the higher stability of the peroxide complexes [25-27]. Oxo complexes are more stable than the binary fluorides. The experimentally characterized iron fluoride with the highest oxidation state is FeF3. The fluoride compound FeF4 was reported in 2003 by FTIR spectroscopy and Knudsen effusion spectrometry [28]. A hexafluoro ferrate compound Cs2FeF6 was reported, which was synthesized in the presence of high pressure and temperature [29].

Cobalt (Co)

The highest oxidation state of cobalt is V. A tetrafluoride complex of cobalt, [CoF4]+, is isolated and characterized by mass spectrometry in the gas phase. It is formed from TbF4 and CoF3 [30, 31]. The highest attainable oxidation state is IV in the case of homoleptic fluorocarbonte anion [CoF6]²- as its K+, Rb+, and Cs+ salts [32]. The highest oxidation state for a binary cobalt fluoride was reported as CoF3. Numerous Co(V) organometallic complexes are reported in the literature. The cobalt complex with four norbornyl ligands in the case of (Co(1-norbornyl)4]BF4 is a low spin, tetrahedral complex with d⁴ configuration [33-35].

Nickel (Ni)

The highest oxidation state of Ni is IV, as shown by a nickel fluoride complex, [NiF6]²-, [36] and NiF4. The latter is known as the strongest oxidizing agent, and the solvation of Ni (IV) in anhydrous HF is comparatively more reactive [37]. The metal complexes of nickel with oxygen are recognized via IR spectroscopy [38]. By vibrational band observation, various Ni (IV) species are suggested in the literature, consisting of peroxo- as in the case of Ni(O2)O complex, Ni(O2)2 di-peroxo complex, and O-Ni-O linear dioxide complex [39, 40]. Some of the vibrational bands also appeared as in the case of Ni(O2)O2 complex, which is also supported by DFT calculation. NiO2 is studied in the gas phase by application of photoelectron spectroscopy [41].

Copper (Cu)

The highest attainable oxidation state of copper is IV, which has been observed by numerous solid-state mixed valence IV/III oxide compounds like NaBa2Cu3O6. The fluoride compounds of copper, such as CuF3,are reported [42]. This fluoride compound of copper is a thermally robust compound and is stable up to 213K. There is no report on the binary fluoride or oxide compounds of copper (IV). But, binary oxide compounds of Cu(III) are present in the literature, such as Cu2O3.

Zinc (Zn)

The only attainable oxidation state of zinc is II. Recently, complexes having metal-metal bonding (Zn–Zn) with a formal oxidation state (I) have been found to be an interesting area of research [43, 44]. As compared to mercury, which is its congener, stabilization is achieved in oxidation state four, which is shown by HgF4. [45, 46] ZnF4 does not exist because of its instability, as there is a susceptible elimination of fluoride. The only fluoride of zinc, ZnF2, exists, and this has been confirmed by IR studies [47].

ELEMENTS OF THE 4D SERIES

The first four elements, Y, Zr, Nb, and Mo, attain the highest oxidant state in their corresponding fluorides, oxyfluorides and oxides compared to the other members of the group.

Technetium (Tc)

It resembles Mn, as its highest attainable oxidation state is seven, which isfound in oxyfluorides [TcO2F4]-, [TcOF4]+, [TcO2F9]+, TcOF5, TcO2F3, TcO3F, pertechnate ion [TcO4]-, and binary oxide Tc2O7 [48]. However, till now, there has been no report of Tc(VII) homoleptic fluoride. The oxo bridge in the dimeric Tc2O7 might be considered as the intermediate between monomeric RuO4 and polymeric MoO3. The NMR characterization of the cation [TcO3]+ revealed that it is in the form of [TcO3][AsF6] [49]. Further, numerous complexes based on alkyloxotechnetium (VII) are produced and subjected to characterization [52, 53]. The highest oxidation state observed in fluoride homoleptic complexes is VI, as seen in TcF6. Many hexafluorides and technetium hexafluorides are presently under reinvestigation by the DFT method and X-ray crystallography [50].

Ruthenium (Ru)

The highest attainable oxidation of Ruthenium is VII, and it is exclusively seen in the case of the tetroxide of ruthenium, which was reported earlier. The molecular structure of this oxide was observed by a single-crystal X-ray diffraction study displaying the existence of the compound in two crystals [51, 52]. This compound was further investigated by other chemical techniques as well as by the quantum chemical method. Also, anions of [Ru (VI)O4]²- and [Ru (VII)O4]- are reported in the literature [53]. These ions are used as oxidizing agents in organic chemistry. Ruthenium octafluoride was observed as a by-product along with the main product RuF5 in the fluorination of RuO2 and Ru. But, this RuF8 compound was not supported by various characterization techniques. Therefore, it is speculated that this fluoride of ruthenium is a mixture of RuO4 and SiF4 [54]. RuF6 is the highest-known ruthenium fluoride, and RuOF4 is the highest-known oxyfluoride.

Rhodium (Rh)

The highest reported attainable oxidation state of Rh is VI, as seen in RhF6 [55]. RhF6's capacity to oxidize oxygen reveals its oxidizing strength [56]. The presence of the RhO2(O2) species, a reaction result of laser-ablated Rh and oxygen, is supported by data [57]. DFT analysis confirmed that this complex is a doublet with oxygen ligands in the terminal position and peroxo- ligand bound to the side, analogous with the iridium complex observed in the same reaction. In terms of rhodium, the relative stability of oxides and fluorides in higher oxidation states demontrates a change in the 4d series, whereas, in species linked with oxygen, fluorides are more stable. The decrease in stability in the oxo complexes is due to the Pauli repulsion taking place among p-orbitals of oxygen and filled d-orbitals of metal, resulting in shorter Rh–O distance.

Palladium (Pd)

The well-established highest attainable oxidation state of palladium is IV, which is shown by [PdX6]²- complexes [58], where X= OH, Cl, F, as in the case of PdF4 [59] and PdO2. PdO2 is reported in the solid state as both a hydrate PdO2.nH2O where n = 1, 2 and as an oxide with a rutile structure free from water [60]. PdO2 molecule is identified by the photoelectron spectroscopy. From DFT calculations, the stability of PdF6 is believed to be established [61]. This theory requires indepth research, as an initial and surface-level investigation is not sufficient. The quantum chemical explanation for PdF6 and its decomposed products is complicated.

Silver (Ag)

The well-established highest attainable oxidation state of silver is III. Ag (III) appears in peroxide or oxides like Ag2O3 [62]. This oxidation state is also shown by the binary fluorides and ion square planar salts [63]. AgF3 can be synthesized by the reaction between fluoride acceptors and [AgF4]– complexes [64]. Ag (III) solvated in the presence of anhydrous HF is the strongest known oxidizer, and another extremely powerful oxidizer is silver trifluoride [65]. Hoffman and Grochala provided a unique report on silver fluoride along with data on superconducting characteristics [66]. In comparison to [CuF6]²-, which is the lighter homologue of Ag(IV), the status of [AgF6]²- or other Ag(IV) is not well established. The oxidation of [AgF4]- by KrF2 was not successful [67]. It is indicated from the quantum chemical calculations that the elimination of fluorine from [AgF6]- may be endothermic in nature [68].

Cadmium (Cd)

Cadmium is sometimes not considered a transition element because it does not contain partially filled or half-filled d-orbitals. It is considered a post-transition element. The highest attainable oxidation state of cadmium is II. Other higher oxidation states of cadmium are not known.

ELEMENTS OF THE 5D SERIES

The elements from rhenium to mercury are discussed here.

Rhenium (Re)

The highest attainable oxidation state of Re is VII, which is exhibited by numerous compounds. The known oxygen compounds with ReVII oxidation state are oxyfluoride, perrhenate anion [ReO4]- [69, 70], and Re2O7 binary oxide [71]. Organometallic compounds of Re(VII) with imido and oxo ligands are reported in the literature to have great synthetic significance. Methylrheniumtrioxide is the most famous complex of this group [72]. The only known transition metal-based heptafluoride is Rhenium heptafluoride [73]. From the data of neutron powder diffraction, it is known that it exhibits a distorted pentagonal pyramidal structure [74]. Salts having cation [ReF6] + along with counter anions [Au2F11]- and [Sb2F11]- are also reported [75]. Rhenium having H- ligands are well established, like CpReH6, [ReH7L2] where L is a phosphine ligand and [ReH9]²- has a trigonal prismatic structure [76].

Osmium (Os)

The highest reported oxidation state for osmium is VIII. It is exhibited by oxyfluorides and its oxides [77]. OsO4 is very stable, and its boiling point is 131.2 οC. Owing to this high boiling point, it can be subjected to well characterization. Os (VIII) oxo anionic complexes, along with hydroxo or nitrido ligands, are also reported [77, 78]. Osmium hexafluoride, OsF6, is the most well characterized fluoride of Os among other fluorides [79]. Presently, octafluoride (OsF8) is not known. The oxyfluoride, OsOF5,has been well studied [80], whereas the reported oxyfluoride, OsOF6,has not been [81, 82]. The synthesis of higher oxyfluoride and