In
materials science, polymorphism describes the existence of a solid material in more than one form or
crystal structure
In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric patterns t ...
. Polymorphism is a form of
isomerism
In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers.
Iso ...
. Any crystalline material can exhibit the phenomenon.
Allotropy
Allotropy or allotropism () is the property of some chemical elements to exist in two or more different forms, in the same physical state, known as allotropes of the elements. Allotropes are different structural modifications of an element: the ...
refers to polymorphism for
chemical element
A chemical element is a species of atoms that have a given number of protons in their nuclei, including the pure substance consisting only of that species. Unlike chemical compounds, chemical elements cannot be broken down into simpler sub ...
s. Polymorphism is of practical relevance to
pharmaceutical
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
s,
agrochemical
An agrochemical or agrichemical, a contraction of ''agricultural chemical'', is a chemical product used in industrial agriculture. Agrichemical refers to biocides (pesticides including insecticides, herbicides, fungicides and nematicides) an ...
s,
pigment
A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic comp ...
s,
dyestuffs,
food
Food is any substance consumed by an organism for nutritional support. Food is usually of plant, animal, or fungal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals. The substance is ...
s, and
explosive
An explosive (or explosive material) is a reactive substance that contains a great amount of potential energy that can produce an explosion if released suddenly, usually accompanied by the production of light, heat, sound, and pressure. An exp ...
s. According to
IUPAC
The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...
, a polymorphic transition is "A reversible transition of a solid crystalline phase at a certain temperature and pressure (the inversion point) to another phase of the same chemical composition with a different crystal structure." According to
McCrone, polymorphs are "different in crystal structure but identical in the liquid or vapor states."
Materials with two polymorphs are called dimorphic, with three polymorphs, trimorphic, etc.
Examples
Many compounds exhibit polymorphism. It has been claimed that "every compound has different polymorphic forms, and that, in general, the number of forms known for a given compound is proportional to the time and money spent in research on that compound."
[
]
Organic compounds
Benzamide
The phenomenon was discovered in 1832 by Friedrich Wöhler
Friedrich Wöhler () FRS(For) HonFRSE (31 July 180023 September 1882) was a German chemist known for his work in inorganic chemistry, being the first to isolate the chemical elements beryllium and yttrium in pure metallic form. He was the first ...
and Justus von Liebig
Justus Freiherr von Liebig (12 May 1803 – 20 April 1873) was a German scientist who made major contributions to agricultural and biology, biological chemistry, and is considered one of the principal founders of organic chemistry. As a profess ...
. They observed that the silky needles of freshly crystallized benzamide
Benzamide is a organic compound with the chemical formula of C6H5C(O)NH2. It is the simplest amide derivative of benzoic acid. In powdered form, it appears as a white solid, while in crystalline form, it appears as colourless crystals. It is slig ...
slowly converted to rhombic crystals. Present-day analysis identifies three polymorphs for benzamide: the least stable one, formed by flash cooling is the orthorhombic
In crystallography, the orthorhombic crystal system is one of the 7 crystal systems. Orthorhombic lattices result from stretching a cubic lattice along two of its orthogonal pairs by two different factors, resulting in a rectangular prism with ...
form II. This type is followed by the monoclinic
In crystallography, the monoclinic crystal system is one of the seven crystal systems. A crystal system is described by three vectors. In the monoclinic system, the crystal is described by vectors of unequal lengths, as in the orthorhombic ...
form III (observed by Wöhler/Liebig). The most stable form is monoclinic
In crystallography, the monoclinic crystal system is one of the seven crystal systems. A crystal system is described by three vectors. In the monoclinic system, the crystal is described by vectors of unequal lengths, as in the orthorhombic ...
form I. The hydrogen bonding mechanisms are the same for all three phases; however, they differ strongly in their pi-pi interactions.
Maleic acid
In 2006 a new polymorph of maleic acid was discovered, fully 124 years after the first crystal form was studied. Maleic acid is manufactured on an industrial scale in the chemical industry. It forms salt found in medicine. The new crystal type is produced when a co-crystal of caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine t ...
and maleic acid (2:1) is dissolved in chloroform
Chloroform, or trichloromethane, is an organic compound with formula C H Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE. It is also a precursor to various re ...
and when the solvent is allowed to evaporate slowly. Whereas form I has monoclinic
In crystallography, the monoclinic crystal system is one of the seven crystal systems. A crystal system is described by three vectors. In the monoclinic system, the crystal is described by vectors of unequal lengths, as in the orthorhombic ...
space group
In mathematics, physics and chemistry, a space group is the symmetry group of an object in space, usually in three dimensions. The elements of a space group (its symmetry operations) are the rigid transformations of an object that leave it ...
''P''21/''c'', the new form has space group ''Pc''. Both polymorphs consist of sheets of molecules connected through hydrogen bond
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing ...
ing of the carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyl ...
groups; but, in form I, the sheets alternate with respect of the net dipole moment, whereas, in form II, the sheets are oriented in the same direction.
1,3,5-Trinitrobenzene
After 125 years of study, 1,3,5-trinitrobenzene yielded a second polymorph. The usual form has the space group ''Pbca'', but in 2004, a second polymorph was obtained in the space group ''Pca''21 when the compound was crystallised in the presence of an additive, trisindane. This experiment shows that additives can induce the appearance of polymorphic forms.
Other organic compounds
Acridine has been obtained as eight polymorphs and aripiprazole has nine. The record for the largest number of well-characterised polymorphs is held by a compound known as ROY. Glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
crystallizes as both monoclinic
In crystallography, the monoclinic crystal system is one of the seven crystal systems. A crystal system is described by three vectors. In the monoclinic system, the crystal is described by vectors of unequal lengths, as in the orthorhombic ...
and hexagonal crystals. Polymorphism in organic compounds is often the result of conformational polymorphism.
Inorganic compounds
Binary metal oxides
Polymorphism in binary metal oxides has attracted much attention because these materials are of significant economic value. One set of famous examples have the composition SiO2, which form many polymorphs. Important ones include: α-quartz, β-quartz, tridymite
Tridymite is a high-temperature polymorph of silica and usually occurs as minute tabular white or colorless pseudo-hexagonal crystals, or scales, in cavities in felsic volcanic rocks. Its chemical formula is Si O2. Tridymite was first described ...
, cristobalite
Cristobalite is a mineral polymorph of silica that is formed at very high temperatures. It has the same chemical formula as quartz, SiO2, but a distinct crystal structure. Both quartz and cristobalite are polymorphs with all the members of the q ...
, moganite
Moganite is an oxide mineral with the chemical formula Si O2 (silicon dioxide) that was discovered in 1976. It was initially described as a new form of silica from specimens found in the Barranco de Medio Almud, in the municipality of Mogán on ...
, coesite, and stishovite.
["Polymorphism in nanocrystalline binary metal oxides", S. Sood, P.Gouma, Nanomaterials and Energy, 2(NME2), 1-15(2013).]
sweater
Other inorganic materials
Classical examples of polymorphism are the pair of minerals calcite
Calcite is a carbonate mineral and the most stable polymorph of calcium carbonate (CaCO3). It is a very common mineral, particularly as a component of limestone. Calcite defines hardness 3 on the Mohs scale of mineral hardness, based on scra ...
and aragonite
Aragonite is a carbonate mineral, one of the three most common naturally occurring crystal forms of calcium carbonate, (the other forms being the minerals calcite and vaterite). It is formed by biological and physical processes, including pre ...
, both forms of calcium carbonate. Perhaps the most famous example is that of the polymorphs of carbon: graphite and diamond.
β-HgS precipitates as a black solid when Hg(II) salts are treated with H2S. With gentle heating of the slurry, the black polymorph converts to the red form.
Factors affecting polymorphism
According to Ostwald's rule, usually less stable polymorphs crystallize before the stable form. The concept hinges on the idea that unstable polymorphs more closely resemble the state in solution, and thus are kinetically advantaged. The founding case of fibrous vs rhombic benzamide illustrates the case. Another example is provided by two polymorphs of titanium dioxide
Titanium dioxide, also known as titanium(IV) oxide or titania , is the inorganic compound with the chemical formula . When used as a pigment, it is called titanium white, Pigment White 6 (PW6), or CI 77891. It is a white solid that is insoluble ...
.[Anatase to Rutile Transformation](_blank)
ART) summarized in the Journal of Materials Science 2011
Polymorphs have disparate stabilities. Some convert rapidly at room (or any) temperature. Most polymorphs of organic molecules only differ by a few kJ/mol in lattice energy. Approximately 50% of known polymorph pairs differ by less than 2 kJ/mol and stability differences of more than 10 kJ/mol are rare.
Polymorphism is affected by the details of crystallisation. The solvent in all respects affects the nature of the polymorph, including concentration, other components of the solvent, i.e., species that inhibiting or promote certain growth patterns. A decisive factor is often the temperature of the solvent from which crystallisation is carried out.
Metastable polymorphs are not always reproducibly obtained, leading to cases of "disappearing polymorphs
In materials science, disappearing polymorphs (or perverse polymorphism) describes a phenomenon in which a seemingly stable crystal structure is suddenly unable to be produced, instead transforming into a polymorph, or differing crystal structur ...
".[Crystal Engineering: The Design and Application of Functional Solids, Volume 539, Kenneth Richard Seddon, Michael Zaworotk 1999]
In pharmaceuticals
Drugs
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalat ...
receive regulatory approval for only a single polymorph. In a classic patent
A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an sufficiency of disclosure, enabling disclo ...
dispute, the GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British Multinational corporation, multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a Mergers and acquisitions, merger of Gl ...
defended its patent for the polymorph type II of the active ingredient in Zantac against competitors while that of the polymorph type I had already expired. Polymorphism in drugs can also have direct medical implications since dissolution rates depend on the polymorph. Polymorphic purity of drug samples can be checked using techniques such as powder X-ray diffraction, IR/Raman
spectroscopy, and utilizing the differences in their optical properties in some cases.
Case studies
Ritonavir
The antiviral drug ritonavir exists as two polymorphs, which differ greatly in efficacy. Such issues were solved by reformulating the medicine into gelcaps and tablets, rather than the original capsules.
Acetylsalicylic acid
A second polymorph of acetylsalicylic acid was reported only in 2005. A new crystal type was found after attempted co-crystallization of aspirin and levetiracetam from hot acetonitrile. In form I, pairs of aspirin molecules form centrosymmetric dimers through the acetyl
In organic chemistry, acetyl is a functional group with the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, acetyl is called ethanoyl ...
groups with the (acidic) methyl proton to carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containin ...
hydrogen bond
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing ...
s. In form II, each aspirin molecule forms the same hydrogen bonds, but with two neighbouring molecules instead of one. With respect to the hydrogen bonds formed by the carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyl ...
groups, both polymorphs form identical dimer structures. The aspirin polymorphs contain identical 2-dimensional sections and are therefore more precisely described as polytypes.
Paracetamol
Paracetamol
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferi ...
powder has poor compression properties, which poses difficulty in making tablets. A second polymorph was found with more suitable compressive properties.
Cortisone acetate
Cortisone
Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug; it is not synthesized in the adrenal glands. Cortisol is converted by the action of the ...
acetate exists in at least five different polymorphs, four of which are unstable in water and change to a stable form.
Carbamazepine
Carbamazepine
Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medi ...
, estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal a ...
, paroxetine, and chloramphenicol
Chloramphenicol is an antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medica ...
also show polymorphism.
Polytypism
Polytypes are a special case of polymorphs, where multiple close-packed crystal structures differ in one dimension only. Polytypes have identical close-packed planes, but differ in the stacking sequence in the third dimension perpendicular to these planes. Silicon carbide (SiC) has more than 170 known polytypes, although most are rare. All the polytypes of SiC have virtually the same density and Gibbs free energy
In thermodynamics, the Gibbs free energy (or Gibbs energy; symbol G) is a thermodynamic potential that can be used to calculate the maximum amount of work (physics), work that may be performed by a closed system, thermodynamically closed system a ...
. The most common SiC polytypes are shown in Table 1.
Table 1: Some polytypes of SiC.
A second group of materials with different polytypes are the transition metal dichalcogenides :image:Cadmium sulfide.jpg, 220px, Cadmium sulfide, a prototypical metal chalcogenide, is used as a yellow pigment.
A chalcogenide is a chemical compound consisting of at least one chalcogen anion and at least one more electropositive element. Altho ...
, layered materials such as molybdenum disulfide (MoS2). For these materials the polytypes have more distinct effects on material properties, e.g. for MoS2, the 1T polytype is metallic in character, while the 2H form is more semiconducting.
Another example is tantalum disulfide, where the common 1T as well as 2H polytypes occur, but also more complex 'mixed coordination' types such as 4Hb and 6R, where the trigonal prismatic and the octahedral geometry layers are mixed. Here, the 1T polytype exhibits a charge density wave, with distinct influence on the conductivity as a function of temperature, while the 2H polytype exhibits superconductivity
Superconductivity is a set of physical properties observed in certain materials where electrical resistance vanishes and magnetic flux fields are expelled from the material. Any material exhibiting these properties is a superconductor. Unlik ...
.
ZnS and CdI2 are also polytypical. It has been suggested that this type of polymorphism is due to kinetics where screw dislocations rapidly reproduce partly disordered sequences in a periodic fashion.
Theory
In terms of thermodynamics
Thermodynamics is a branch of physics that deals with heat, work, and temperature, and their relation to energy, entropy, and the physical properties of matter and radiation. The behavior of these quantities is governed by the four laws o ...
, two types of polymorphic behaviour are recognized. For a monotropic system, plots of the free energies of the various polymorphs against temperature do not cross before all polymorphs melt. As a result any transition from one polymorph to another below the melting point will be irreversible. For an enantiotropic system, a plot of the free energy against temperature shows a crossing point before the various melting points. It may also be possible to convert interchangeably between the two polymorphs by heating or cooling, or through physical contact with a lower energy polymorph.
]
See also
* Isomorphism (crystallography)
* Dimorphism (Wiktionary)
* Polyamorphism
References
External links
"Small Molecule Crystallization"
( PDF) at Illinois Institute of Technology
Illinois Institute of Technology (IIT) is a private research university in Chicago, Illinois. Tracing its history to 1890, the present name was adopted upon the merger of the Armour Institute and Lewis Institute in 1940. The university has pro ...
website
"SiC and Polytpism"
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Mineralogy
Gemology
Crystallography