The term calcium phosphate refers to a family of materials and minerals containing calcium ions (Ca2+) together with inorganic phosphate anions. Some so-called calcium phosphates contain oxide and hydroxides as well. Calcium phosphates are white solids of nutritional value and are found in many living organisms, e.g., bone mineral and tooth enamel.
In milk, it exists in a colloidal form in micelles bound to casein protein with magnesium, zinc, and citrate–collectively referred to as colloidal calcium phosphate (CCP). Various calcium phosphate minerals, which often are not white owing to impurities, are used in the production of phosphoric acid and fertilizers.
Calcium Phosphate (Ca3(PO4)2): Structure
Chemical Formula and Composition:
- Formula: Ca₃(PO₄)₂
- Composition: Three calcium ions (Ca²⁺) and two phosphate ions (PO₄³⁻) per formula unit, resulting in a neutral compound.
Crystal Structures: Calcium phosphate can form several crystalline structures, but we’ll focus on the most relevant ones:
Hydroxyapatite (HAp):
- Formula: Ca₁₀(PO₄)₆(OH)₂, this is the predominant form in biological systems.
- Crystal System: Hexagonal.
- Structure:
- Hydroxyapatite has a hexagonal lattice in which calcium ions are surrounded by oxygen atoms from the phosphate groups and hydroxyl groups. The basic building blocks are Ca₅(PO₄)₃OH units, which are stacked in layers.
- The calcium ions occupy two different types of sites: one with nine-fold coordination and another with seven-fold coordination to oxygen atoms.
- The hydroxyl ions are positioned along the c-axis of the crystal, creating channels where ions or water molecules can move or be replaced by other anions like fluoride (F⁻) or chloride (Cl⁻), altering the properties of the material.
- Unit Cell: The hexagonal unit cell contains 10 calcium atoms, 6 phosphate groups, and 2 OH⁻ ions.
Whitlockite:
- Formula: Ca₉(Mg,Fe)(PO₄)₇, a magnesium or iron-substituted form of tricalcium phosphate (TCP).
- Crystal System: Rhombohedral.
- Structure: Whitlockite has a structure similar to β-TCP but with some calcium sites substituted by magnesium or iron, which affects the lattice parameters and stability.
Tricalcium Phosphate (TCP):
- Formula: Ca₃(PO₄)₂ exists in two main forms:
- α-TCP: A high-temperature phase, monoclinic or hexagonal depending on conditions.
- β-TCP: The stable phase at room temperature, rhombohedral structure.
- Structure: In β-TCP, calcium ions are coordinated by 7 or 8 oxygen atoms. The structure consists of PO₄ tetrahedra linked by Ca-O bonds, forming a network with large cavities.
Atomic Arrangement:
- Phosphate Tetrahedra: Each phosphorus atom is at the center of a tetrahedron surrounded by four oxygen atoms. These tetrahedra are the basic structural units of calcium phosphates.
- Calcium Coordination: Calcium ions are in various coordination environments with oxygen atoms, which can range from 6 to 9 in hydroxyapatite, creating a versatile and adaptable crystal structure.
Structural Flexibility:
- The structure of calcium phosphate, especially hydroxyapatite, allows for significant ionic substitution, which can modify its chemical and physical properties. For instance, fluoride or carbonate ions can substitute for hydroxyl or phosphate groups, respectively, affecting the material’s solubility, strength, and bioactivity.
Calcium Phosphate (Ca3(PO4)2): Properties
Calcium Phosphate (Ca₃(PO₄)₂): Detailed Properties
Physical Properties:
Appearance:
- Color: White or colorless when pure.
- Form: Powder or crystalline solid.
Density:
- Density: Varies with crystal form; for hydroxyapatite, approximately 3.16 g/cm³.
Melting Point:
- Decomposition: Does not have a distinct melting point; decomposes at about 1670°C.
Solubility:
- In Water: Sparingly soluble at neutral pH (0.002 g/L at 25°C).
- Acidic Environment: Solubility increases dramatically; it acts as a buffer and can dissolve to form calcium dihydrogen phosphate, which is more soluble.
- Effect of Temperature: Solubility generally increases with temperature.
Crystal Structure:
- Polymorphism: Exists in various forms like hydroxyapatite, tricalcium phosphate (α and β forms), and whitlockite, each with different crystal structures (hexagonal, monoclinic, rhombohedral).
Chemical Properties:
Stability:
- Thermal Stability: Stable at room temperature but decomposes at high temperatures.
- Chemical Stability: Stable under normal conditions; however, it reacts with acids to release phosphoric acid and calcium salts.
pH Influence:
- Buffering Capacity: Acts as a buffer in biological systems, helping to maintain pH levels in bone and blood. The solubility product is pH-dependent, making it less soluble as pH increases.
Reactivity:
- Acid-Base Reactions: Reacts with strong acids to form soluble calcium salts: Ca3(PO4)2+6HCl→3CaCl2+2H3PO4
- Ion Exchange: In hydroxyapatite, OH⁻ ions can be replaced by other anions like F⁻, increasing stability and reducing solubility.
Biological Activity:
- Biocompatibility: Highly biocompatible due to its natural occurrence in bone and teeth.
- Osteoconductivity: Encourages bone growth by providing a scaffold for new bone formation.
Mechanical Properties:
Hardness:
- Mohs Hardness: Varies, but hydroxyapatite is relatively hard (5-6 on the Mohs scale).
Compressive Strength:
- When used in bone repair or as coatings on implants, the strength can be tailored by composition and processing methods; pure hydroxyapatite has moderate compressive strength.
Elastic Modulus:
- Similar to bone; hydroxyapatite has an elastic modulus that allows it to mimic bone behavior under stress.
Electrical and Optical Properties:
Dielectric Properties:
- Used in electronic applications due to its dielectric properties in some of its forms.
Optical:
- Generally opaque in bulk form but can be translucent when finely powdered.
Thermal Properties:
Thermal Conductivity:
- Relatively low, which is advantageous for certain applications where heat dissipation is not desired.
Thermal Expansion:
- The coefficient of thermal expansion is low, which is beneficial for applications involving temperature changes.
Additional Properties:
- Magnetic Properties: Not magnetic in its common forms.
- Toxicity: Non-toxic, making it suitable for biomedical applications.
Calcium Phosphate (Ca3(PO4)2): Preparation
Precipitation Method:
- Reactants: Typically involves mixing solutions of a soluble calcium salt (e.g., calcium nitrate, Ca(NO₃)₂, or calcium chloride, CaCl₂) with a phosphate source (such as sodium phosphate, Na₃PO₄, or ammonium phosphate, (NH₄)₃PO₄).
- Procedure:
- Solution Preparation: Prepare solutions of calcium and phosphate salts in deionized water or appropriate solvents.
- pH Control: Adjust the pH of the solution to control the precipitation. Calcium phosphate is less soluble at neutral to slightly alkaline pH, so you might adjust to pH 7-9.
- Mixing: Slowly add the phosphate solution to the calcium solution under constant stirring to ensure uniform precipitation.
- Aging: Allow the precipitate to age for several hours to days to improve crystallinity or particle size distribution.
- Washing: Wash the precipitate thoroughly to remove any by-products (like sodium nitrate if sodium phosphate was used).
- Drying: Dry the precipitate at controlled temperatures (e.g., 60-100°C) to remove moisture without altering the chemical composition.
- Optional Calcination: For some applications, calcining at higher temperatures (e.g., 900-1200°C) can be done to convert the precipitate into a more stable or desired crystalline form like hydroxyapatite or β-TCP.
Hydrothermal Synthesis:
- Reactants: Similar to precipitation but performed under high pressure and temperature to control crystal growth.
- Procedure:
- Solution Preparation: Combine calcium and phosphate salts in water in a sealed autoclave.
- Temperature and Pressure: Heat the mixture to 100-250°C under pressure, which can be as high as the vapor pressure of water at that temperature. This allows for the synthesis of well-crystallized hydroxyapatite or other forms.
- Crystal Growth: The hydrothermal environment promotes the formation of larger and more uniform crystals.
- Cooling: Gradually cool the system to room temperature to avoid thermal shock to the crystals.
- Processing: The product is then washed, filtered, and dried.
Sol-Gel Method:
- Reactants: Uses alkoxides or nitrates of calcium and phosphorus precursors.
- Procedure:
- Hydrolysis and Condensation: Calcium and phosphorus precursors are mixed with water or an alcohol solution, leading to hydrolysis and condensation reactions to form a gel.
- Gelation: The solution turns into a gel, which traps the calcium and phosphate ions in a network.
- Aging: The gel is aged to strengthen the structure.
- Drying: Carefully dry the gel, often supercritically to avoid cracking, yielding an amorphous or poorly crystalline phase.
- Heat Treatment: Subsequent heat treatment at elevated temperatures leads to crystallization into various forms of calcium phosphate.
Solid-State Reaction:
- Reactants: Direct reaction between solid calcium and phosphate compounds (like calcium carbonate and ammonium dihydrogen phosphate).
- Procedure:
- Mixing: Thoroughly mix the reactants in a stoichiometric ratio.
- Heat: Heat the mixture at high temperatures (e.g., above 1000°C) for solid-state diffusion to occur.
- Grinding: After cooling, grind the product to ensure homogeneity.
Chemical Vapor Deposition or Spray Pyrolysis:
- Reactants: Volatile calcium and phosphate sources are used.
- Procedure:
- Vaporization: Precursor vapors are introduced into a reactor where they react or decompose on a substrate at high temperatures.
Calcium Phosphate (Ca3(PO4)2): Preparation
- Bone Substitutes and Bone Grafts: Due to its similarity to natural bone mineral, hydroxyapatite, a form of calcium phosphate, is widely used as a bone substitute in orthopedic and dental surgeries.
- Dental Applications: Used in dental implants, fillings, and as a component in toothpaste to remineralize tooth enamel.
- Calcium Supplements: As a source of calcium for dietary supplements, helping in the prevention and treatment of calcium deficiencies.
- Pharmaceuticals: Acts as an excipient in pharmaceuticals, particularly in tablets where it serves as a filler, binder, or disintegrant.
- Antacids: Some antacids contain calcium phosphate to neutralize stomach acid, providing relief from heartburn and aiding in digestion.
- Food Additive: Known as E341, it’s used in the food industry as an acidity regulator, firming agent, and to prevent caking in powdered foods.
- Animal Feed: Added to animal feeds to supply necessary calcium and phosphorus for bone development and overall health in livestock.
- Fertilizers: In agriculture, calcium phosphate provides both calcium and phosphorus, essential nutrients for plant growth.
- Ceramics: Used in the manufacture of bioceramics for implants or in high-temperature applications where stability is required.
- Water Treatment: Applied in water treatment processes for the removal of heavy metals or phosphates through precipitation.
- Cosmetics: In cosmetics, particularly in toothpastes and some skincare products for its mineralizing or stabilizing effects.
- Gene Delivery Systems: Calcium phosphate nanoparticles can be used as vectors in gene therapy for delivering genetic material into cells without significant toxicity.