PHD
  1. Inorganic chemistry  1.1. Coordination chemistry  1.1.1. Ligand field theory  1.1.2. Crystal field theory  1.1.3. Molecular Orbital Theory for Coordination Compounds  1.1.4. Stability of Coordination Compounds  1.1.5. Electronic spectra of coordination compounds  1.1.6. Isomerism in Coordination Compounds  1.1.7. Kinetics and mechanism of coordination reactions  1.2. Organometallic Chemistry  1.2.1. Metal Carbonyls  1.2.2. Metal alkyl and aryl  1.2.3. Fischer and Schrock carbonaceans  1.2.4. Oxidative Addition and Reductive Elimination  1.2.5. Metal Hydrides  1.2.6. Catalysis by organometallic compounds  1.2.7. Metallocenes and Sandwich Complexes  1.2.8. CH activation  1.3. Solid state chemistry  1.3.1. Crystal structures and lattices  1.3.2. Band theory and electrical properties  1.3.3. Defects in the crystal  1.3.4. Synthesis of solid state materials  1.3.5. Magnetic and optical properties of solids  1.3.6. Superconductivity  1.3.7. Solid state ionics  1.4. Bio-inorganic chemistry  1.4.1. Metalloproteins and enzymes  1.4.2. Metal ion transport and storage  1.4.3. The role of metals in medicine  1.4.4. Bioinspired catalysis  1.4.5. Metal–DNA interactions  1.4.6. Metal Complexes in Medical Science  1.5. Lanthanides and Actinides  1.5.1. Electronic configuration and oxidation states in lanthanides and actinides  1.5.2. Spectral and Magnetic Properties in Lanthanides and Actinides  1.5.3. Separation and Extraction of Lanthanides and Actinides  1.5.4. Coordination chemistry of f-block elements  1.6. Main Group Chemistry  1.6.1. Chemistry of boron compounds  1.6.2. Chemistry of Silicon and Germanium Compounds  1.6.3. Chemistry of Phosphorus and Sulfur Compounds  1.6.4. Organosilicon chemistry  1.6.5. Noble Gas Chemistry
  2. Organic chemistry  2.1. Reaction mechanism  2.1.1. Nucleophilic substitution reactions  2.1.2. Electrophilic addition and substitution reactions  2.1.3. Elimination reactions  2.1.4. Rearrangement reactions  2.1.5. Radical reactions  2.1.6. Pericyclic Reactions  2.1.7. Photochemical reactions  2.2. Stereoscopic  2.2.1. Chirality and optical activity  2.2.2. Structural analysis  2.2.3. Stereoelectronic effects  2.2.4. Asymmetric synthesis  2.2.5. Dynamic Stereochemistry  2.3. Organometallic Chemistry in Organic Synthesis  2.3.1. Organolithium and organomagnesium reagents  2.3.2. Transition metal catalyzed coupling reactions  2.3.3. Palladium-catalyzed reactions  2.3.4. Olefin Metathesis  2.3.5. Gold and silver catalysis  2.4. Natural products chemistry  2.4.1. Alkaloids and terpenoids  2.4.2. Steroids and Flavonoids  2.4.3. Total synthesis of natural products  2.4.4. Biosynthesis of natural products  2.5. Supramolecular Chemistry  2.5.1. Host-Guest Chemistry  2.5.2. Self-assembly and molecular recognition  2.5.3. Supramolecular Catalysis  2.5.4. Molecular Machines
  3. Physical Chemistry  3.1. Thermodynamics  3.1.1. Laws of Thermodynamics  3.1.2. Chemical Potential and Equilibrium  3.1.3. Statistical thermodynamics  3.1.4. Non-equilibrium thermodynamics  3.2. Quantum Chemistry  3.2.1. Schrödinger equation and its applications  3.2.2. Molecular orbital theory  3.2.3. Density functional theory  3.2.4. Post-Hartree–Fock methods  3.3. Chemical kinetics  3.3.1. Reaction rate theory  3.3.2. Mechanism and rate laws  3.3.3. Catalysis and enzyme kinetics  3.3.4. Reaction dynamics  3.4. Spectroscopy and molecular structure  3.4.1. Infrared Spectroscopy  3.4.2. UV-visible spectroscopy  3.4.3. Nuclear Magnetic Resonance Spectroscopy  3.4.4. Mass Spectrometry  3.4.5. Raman Spectroscopy  3.5. Surface and Colloid Chemistry  3.5.1. Absorption and Catalysis  3.5.2. Surfactants and micelles  3.5.3. Colloidal Stability  3.5.4. Nanomaterials and Interfaces
  4. Analytical chemistry  4.1. Chromatography  4.1.1. Gas Chromatography  4.1.2. High Performance Liquid Chromatography  4.1.3. Thin Layer Chromatography  4.1.4. Ion Chromatography  4.2. Electroanalytical techniques  4.2.1. Voltammetry and Polarography  4.2.2. Conductometry and potentiometry  4.2.3. Colometry  4.3. Spectroscopic Methods  4.3.1. Atomic absorption spectroscopy  4.3.2. Fluorescence Spectroscopy  4.3.3. X-ray diffraction  4.3.4. Electron paramagnetic resonance spectroscopy  4.4. Chemometrics  4.4.1. Data processing and statistical methods  4.4.2. Multidisciplinary analysis  4.4.3. Machine Learning in Analytical Chemistry
  5. Theoretical and Computational Chemistry  5.1. Molecular dynamics simulation  5.2. Quantum chemistry methods  5.3. Computational drug design  5.4. Machine Learning in Chemistry  5.5. Ab initio molecular dynamics
  6. Biophysics and Medicinal Chemistry  6.1. Drug discovery and design  6.2. Enzyme kinetics and inhibition  6.3. Chemical biology approach  6.4. Protein-ligand interactions  6.5. Bioorthogonal chemistry
  7. Materials chemistry  7.1. Polymer chemistry  7.1.1. Polymerization mechanism  7.1.2. Functional Polymers  7.1.3. Biodegradable Polymer  7.1.4. Conducting and semiconducting polymers  7.2. Nano Chemistry  7.2.1. Nanoparticles and nanostructures  7.2.2. Carbon-based nanomaterials  7.2.3. Quantum dots  7.3. Energy and Environmental Chemistry  7.3.1. Battery and Fuel Cell Chemistry  7.3.2. Green chemistry and sustainable materials  7.3.3. Photocatalysis

PHD → Inorganic chemistry → Bio-inorganic chemistry ↓


Metal Complexes in Medical Science


Understanding metal complexes

Metal complexes are unique compounds that form when metal ions combine with ligands – molecules or ions that can donate a pair of electrons to the metal. This coordination gives metal complexes unique physical and chemical properties that are used in a variety of applications, including medicine. In the field of medicine, metal complexes have inspired significant advances, especially in the treatment and management of diseases.

Metal ions Ligands

Metal complexes can have various geometries, such as octahedral, tetrahedral or square planar, depending on the number and arrangement of ligands around the central metal ion. Here is a simplified representation of an octahedral complex, which typically consists of six ligands around a central metal ion.

Historical perspective and biological significance

Traditionally, metals were often considered toxic in biological systems. However, the discovery of the anti-cancer properties of the platinum complex cisplatin highlighted the potential of metal complexes in medicinal chemistry. This compound had profound inhibitory effects on cancer cells, leading to its acceptance for the treatment of various cancers.

Pt(NH₃)₂Cl₂ - Cisplatin

The significance of this discovery inspired further research into other metal complexes with potential therapeutic benefits. The unique properties of metals, such as variable oxidation states and the ability to form stable, yet reversible, interactions, give them distinct advantages in biological systems.

Methodology

One of the most fascinating aspects of metal complexes in medical science is their mechanism of action. These mechanisms vary depending on the metal ion and the ligand involved. Metal complexes can perform the following functions:

  • Interact with DNA and inhibit replication and transcription processes.
  • Generate reactive oxygen species that produce oxidative stress and damage cellular components.
  • Act as enzyme inhibitors, modifying metabolic pathways.
  • Mimicking endogenous metals in enzymes, acting as cofactors for essential biological processes.

DNA binding and dissociation

Many metal complexes exert their therapeutic effects by interacting with DNA. For example, cisplatin works by forming covalent bonds with DNA bases, primarily adenine and guanine. This interaction results in the twisting of the DNA helix, thereby inhibiting replication and transcription.

DNA helix Cisplatin

Enzyme inhibition and metal replacement

Metal complexes can also inhibit or mimic enzymes important for disease progression. Enzymes often require metal ions as cofactors. Introducing metal complexes can inhibit enzyme activity or replace the native metal in the enzyme, altering its function and affecting pathogen survival.

Applications of metal complexes in medicine

Apart from cancer treatment, metal complexes are also used in various medical fields. Their potential role extends to antimicrobial, anti-inflammatory and diagnostic applications. Here are some prominent examples:

Cancer therapy

Following the success of cisplatin, other platinum-based complexes such as carboplatin and oxaliplatin have been developed. These compounds address the limitations of cisplatin, such as fewer side effects and greater efficacy against resistant cancer cells. 

Carboplatin: [Pt(NH₃)₂(CBDCA)]
Oxaliplatin: [Pt(DACH)(oxalate)]

Antimicrobial activity

Metal alloys have proven effective against a wide variety of microorganisms. For example, alloys of silver and copper have significant antibacterial properties. These alloys can destroy microbial cell membranes, affecting cell integrity and function. Additionally, gold alloys have shown promise in fighting resistant strains of bacteria, demonstrating greater stability and lower toxicity than conventional antibiotics.

Challenges and future prospects

Despite their efficacy, deploying metal complexes in therapy comes with challenges. Issues such as metal toxicity, selectivity, potential for resistance development, and bioavailability need to be addressed. Ongoing research is focused on developing complexes with enhanced specificity, minimizing undue side effects while enhancing therapeutic benefits. Nanotechnology plays a key role in devising new delivery mechanisms for metal complexes, reducing systemic exposure, and optimizing therapeutic effects. Innovations in ligand design are equally imperative. By optimizing the ligand structure, researchers can modify the release rates of metal ions, improve complex stability, and ameliorate cytotoxicity.

In conclusion, metal complexes represent a frontier in therapeutics. Their unique mechanisms and versatility open new avenues for treating challenging diseases. With advances in our understanding of bio-inorganic chemistry and sophisticated design strategies, the future of metal complexes in therapeutics looks promising and is poised for transformative effects in medicine.


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