Calcium carbonates of altered crystal habit or morphology and methods for producing same

Methods are disclosed in which first and second reactant salts and, optionally, a complexing agent are added to a non-aqueous reaction solvent to form a reaction system. The reactant salts, which are substantially soluble and reactive with each other in water to form a first crystallite of calcium carbonate, are present in the reaction solvent in relative amounts that are sufficient to form a desired amount of the calcium carbonate in the reaction system. The complexing agent, if present, is a crown ether or other cyclic or acyclic polydentate chelating agent that, in the reaction solvent, forms chelation complexes with at least one of the reactant salts. Reaction of the first and second reactant salts in the reaction solvent forms a second crystallite precipitate comprising crystals of calcium carbonate having a different habit or morphology from calcium carbonate crystals in the first crystallite that would otherwise be formable in water by reaction of similar amounts of the first and second reactant salts.

FIELD OF THE INVENTION 
This invention pertains to new crystalline forms of calcium carbonate 
compounds and methods for their preparation. 
BACKGROUND OF THE INVENTION 
Interest in crystallization, and in various ways for altering the shapes 
and structures of crystals, has a long history because an extraordinary 
range of physical and chemical properties of crystalline solid-state 
materials is dictated to a large extent by their crystal form and size. 
Efforts to modify crystallization processes so as to generate new 
crystalline forms of substances continue to be of considerable importance 
for various reasons including, for example, improvement of mass-handling 
characteristics of particulate materials, production of materials that are 
stronger or more durable than existing materials, and production of 
materials having improved physical characteristics such as light 
transmissivity. 
Conventional ways of altering the shape (i.e., the "habit") or the crystal 
lattice (i.e., the "morphology") of a crystalline material include: (1) 
using additives (Weissbuch et al., Science 253:637, 1991; Addadi et al., 
Topics in Stereochem. 16:1, 1986; Addadi et al., Angew. Chem. mnt. Ed. 
Engl. 24:466, 1985; and Addadi et al., Nature 296:21, 1982); and (2) 
changing the crystallization solvent (including crystallization from the 
gas phase) used to dissolve the crystallization solute. Unfortunately, 
these methods are not universally applicable and frequently do not produce 
the desired form of a compound. 
U.S. Pat. No. 5,545,394 to Doxsee, incorporated herein by reference, is 
directed, inter alia, to methods for forming crystallite products by 
chemical reaction. A representative method involves a reaction between a 
first and a second reactant salt in an organic solvent in the presence of 
a complexing agent. The first reactant salt is substantially soluble in 
water but is poorly soluble to insoluble in the organic solvent. The 
second reactant salt is reactive with the first reactant salt in water to 
form a first crystallite of a product compound. The complexing agent is 
soluble in the organic solvent and can form chelation complexes with the 
first reactant salt so as to facilitate, for example, dissolution of the 
first reactant salt in the organic solvent. The reaction results in 
formation of a second crystallite, substantially insoluble in the organic 
solvent, comprising crystals of the product compound that have a different 
habit or morphology from crystals of the product compound in the first 
crystallite that otherwise would be formable in water by reaction of the 
first and second reactant salts without the complexing agent. 
Many salts that are substantially soluble in water are poorly soluble to 
insoluble in many organic solvents. Solvent effects on the alteration of 
crystal growth of such salts have not been explored to any great extent 
simply because one must dissolve the salt before it can be crystallized 
from solution. Calcium carbonate is second only to silica in the mineral 
kingdom in terms of natural abundance. Berry et al., Mineralogy, 2d ed., 
ch. 12, Freeman, San Francisco, 1983. It represents an important 
commercial product, particularly in the paper and plastics industries, 
where it serves as a filler, and in the pharmaceutical industry, where it 
often serves as a binder. Carr et al., in Howe-Grant (ed.), Kirk-Othmer 
Encyclopedia of Chemical Technology, 4th ed., pp. 796-801, Wiley, New 
York, 1992. Calcium carbonate also occupies a position of prominence as 
the most common biomineral, serving as a primary structural component in 
23 of the 31 phyla of organisms that use biominerals. Lowenstam et al., On 
Biomineralization, ch. 1, Oxford Univ. Press, New York, 1989. 
Three anhydrous phases of calcium carbonate are known: calcite, aragonite, 
and vaterite (Eriksson, Rocks and Minerals 70:217-231, 1995; and Deer et 
al., An Introduction to the Rock-Forming Minerals, pt. 5, ch. 5, Wiley, 
New York, 1966), and development of control over and understanding of the 
formation of these phases, as well as over crystal habit (form) remain 
important issues both in industry and in the research area of 
biomineralization. 
The crystallization of calcium carbonate has been heavily studied. Sabbides 
et al., J. Crystal Growth 133:13-22, 1993; Brown et al., J. Colloid 
Interface Sci. 160:372-379, 1993; Wakita et al., J. Crystal Growth 
71:807-809, 1985; and Henisch, Crystals in Gels and Liesegang Rings, 
Cambridge Univ. Press, 1988. Nevertheless, there remains an urgent need 
for other forms of calcium carbonate. 
Therefore, there is a need for methods for producing, via 
reaction-crystallization, calcium carbonates comprising crystals that are 
different in habit and/or morphology from calcium carbonates produced by 
simple crystallization from aqueous solution. There is also a need for 
calcium carbonates having altered habit and/or morphology. 
SUMMARY OF THE INVENTION 
The foregoing needs are met by the present invention that provides, inter 
alia, methods and reaction systems for forming calcium carbonate 
crystallites having altered habit and/or morphology. Also provided are 
calcium carbonate crystallites formed by such methods. 
In a general method according to the present invention, first and second 
reactant salts are added to a non-aqueous reaction solvent to form a 
reaction system. The reactant salts are substantially soluble and reactive 
with each other in water to form a first crystallite of calcium carbonate, 
and are added to the reaction solvent in relative amounts that are 
sufficient for reaction of the first and second reactant salts with each 
other in the reaction system to form a desired amount of the calcium 
carbonate. 
A complexing agent can also be added to the reaction solvent along with the 
first and second reactant salts. The complexing agent, if present, is 
soluble in the reaction solvent and is selected from a group consisting of 
crown ethers and other cyclic and acyclic polydentate chelating agents. 
Also, the complexing agent, if present, is capable of forming chelation 
complexes with at least one of the reactant salts in the reaction solvent. 
In the reaction system, the first and second reactant salts are allowed to 
react with each other to form a second crystallite precipitate. The second 
crystallite comprises crystals of calcium carbonate that have a different 
habit or morphology from calcium carbonate crystals in the calcium 
carbonate in the first crystallite that would otherwise be formable in 
water by reaction of similar amounts of the first and second reactant 
salts. 
The foregoing and other features and advantages of the present invention 
readily can be ascertained from the following description and accompanying 
drawings.

DETAILED DESCRIPTION 
"Complexation-mediated crystallization" is discussed in Doxsee et al., J. 
Inclus. Phenom. & Molec. Recog. in Chem. 9:327-336 (1990), incorporated 
herein by reference. In such methods, a complexing agent (e.g., a crown 
ether that is soluble in a non-aqueous solvent) is used to facilitate 
dissolution of a salt, freely soluble in water, in the non-aqueous 
solvent, wherein the salt is subsequently crystallized from the 
non-aqueous solvent. During the dissolution step, molecules of the 
complexing agent form complexes with one or more of the constituent ions 
of the salt, thereby enabling the salt to "dissolve" (while still 
complexed with the crown ether) in the non-aqueous solvent. Subsequent 
evaporation of the solvent results in crystallization of the salt. With 
respect to an example involving sodium acetate, rather than a typical 
hexagonal plate habit characteristic of sodium acetate trihydrate crystals 
formed from aqueous solution, the crystals formed in the non-aqueous 
solvent have a needle shape but have the same lattice parameters as 
hexagonal plate crystals of sodium acetate. The non-aqueous solvent 
apparently exerts a pronounced salvation effect on the relatively 
non-polar lateral crystal faces (on which van der Waals contacts between 
methyl groups of the acetates apparently predominate) but comparatively 
little salvation effect on the relatively polar axial faces (built up of 
alternating layers of Na.sup.+ ions, water molecules, and acetate 
carboxylates). Thus, the axial faces are caused to grow more rapidly than 
the lateral faces. 
The present invention provides a way to produce crystalline calcium 
carbonates (i.e., "crystallites" of calcium carbonate) by chemical 
reaction, not merely by recrystallization from a solution. In a reaction 
according to the present invention, product calcium carbonate crystals are 
formed that have an altered crystal shape (crystal habit) and/or crystal 
lattice structure (crystal morphology) compared to calcium carbonate 
crystals formed by conventional methods. 
A "reaction system" for forming calcium carbonates according to the present 
invention comprises: (1) reactant salts capable of forming calcium 
carbonate by chemical reaction, and (2) a non-aqueous solvent (termed 
herein the "reaction solvent") in which one or more of the reactant salts 
are to be dissolved (but in which one or more of the reactant salts may 
not be freely soluble). Especially if at least one of the reactant salts 
is poorly soluble to insoluble in the reaction solvent, a "complexing 
agent" suitable for effecting dissolution of at least one of the reactant 
salts in the non-aqueous solvent can be included in the reaction system. 
(Even if the reactant salts are adequately soluble in the reaction 
solvent, a complexing agent can be included in the reaction system to 
effect a change in crystal habit or morphology relative to a reaction 
solvent without a complexing agent and/or relative to a control reaction 
involving the same reactant salts but performed in an aqueous solvent.) 
The reactant salts, reaction solvent, and complexing agent are discussed 
in further detail below. 
A chemical reaction according to the present invention involves molecules 
and/or ions of at least two reactant salts that are presented to each 
other for reaction while in a dissolved condition. Interaction of the 
reactant salts can occur by interdiffusion which can occur in a completely 
liquid medium or in a supported medium such as a gel. (Examples of growth 
of calcium carbonate in a gel can be found in Examples 45 and 46 of U.S. 
Pat. No. 5,545,394, incorporated herein by reference, in which the calcium 
source was calcium chloride, the carbonate source was ammonium carbonate, 
and the gel was a poly(vinylchloride) gel in dimethylsulfoxide.) 
Whenever dissolution of a reactant salt in the reaction solvent is 
facilitated by use of a complexing agent, it is not necessary that all the 
reactant salt be dissolved before the onset of reaction. The complexing 
agent is typically not consumed during the reaction and can therefore 
serve as a "dissolution catalyst" for the corresponding reactant salt. As 
molecules or ions of the reactant salt dissociate from molecules of the 
complexing agent and become incorporated into the calcium carbonate 
product, the liberated molecules of the completing agent become free to 
facilitate dissolution of more of the remaining unreacted reactant salt. 
Thus, the complexing agent can be present in a "catalytic" (i.e., 
sub-stoichiometric) amount in the reaction system. 
As the reaction progresses, the calcium carbonate product forms as one or 
more crystalline masses (crystallites) that precipitate and are thus 
readily separable from the reaction solvent using conventional separation 
techniques. The crystallite can be comprised of visually discernable 
crystals or of crystals that are so small that the crystallite appears to 
be amorphous. 
A key factor in determining whether or not a reactant salt will dissolve in 
a particular reaction solvent is the polarity of the molecules or ions of 
the reactant salt relative to molecules of the reaction solvent. In 
general, reactant salts having polar moieties have a higher solubility in 
polar solvents compared to reactant salts having mostly substantially 
non-polar moieties. Thus, at a given temperature, a greater amount of a 
polar reactant salt will dissolve in a polar solvent than in a relatively 
less polar solvent. The complexing agent, by bonding to the reactant salt, 
can substantially alter the polarity of the reactant salt, usually by 
making the molecules (or constituent ions) of the reactant salt less 
polar. 
Most reactant salts usable for producing calcium carbonate are normally 
soluble in water and have either limited solubility or substantial 
insolubility in less polar solvents. 
As used herein, a "non-aqueous reaction solvent" is a solvent other than 
substantially pure water. In order to dissolve a reactant salt in such a 
solvent sufficiently for the desired reaction to occur between reactant 
salts, a complexing agent can be used that is soluble in the non-aqueous 
reaction solvent and that can form a complex with the reactant salt to be 
dissolved in the non-aqueous reaction solvent. 
It is possible for a first reactant salt to be soluble in the reaction 
solvent and a second reactant salt to have limited solubility in the 
reaction solvent. In such an instance, a complexing agent can be used to 
facilitate dissolution of the second reactant salt in the reaction 
solvent. 
It is also possible for both reactant salts to be soluble in the reaction 
solvent. In such an instance, the complexing agent can be used to alter 
the habit and/or morphology of the crystallite product. 
Reaction systems according to the present invention also encompass systems 
in which both the first and second reactant salts require complexing 
agents for dissolution. The complexing agents can be the same or 
different. In a representative example of such a system, a first solution 
containing a first complexed reactant salt is layered atop a second 
solution containing a second complexed reactant salt, wherein the reaction 
occurs at the interface of the first and second solutions. Additional 
"phases" are also possible. 
It is not necessary that the reaction system comprise a phase interface at 
all. "Single-phase" reactions in a single reaction solvent comprising all 
the reactant salts are within the scope of the present invention. 
The complexing agent performs at least one of the following roles: (a) 
solubilizing a reactant salt in the reaction solvent; and (b) influencing 
the habit and/or morphology of the crystalline calcium carbonate product 
formed in the reaction solvent, presumably by affecting the differential 
rates of growth of certain crystal faces relative to other crystal faces. 
In reaction systems in which both reactant salts, in the absence of the 
complexing agent, are insoluble in the reaction solvent, the complexing 
agent generally performs both roles. In reaction systems in which one 
reactant salt is insoluble in the reaction solvent and requires 
complexation with the complexing agent in order to be dissolved in the 
reaction solvent, but the other reactant salt is soluble in the reaction 
solvent, the complexing agent again performs both roles. In reaction 
systems in which both reactant salts are sufficiently soluble in the 
reaction solvent for the reaction to occur, the complexing agent serves 
mainly the second role. 
A molecule of the complexing agent can facilitate dissolution of a molecule 
or ion of a reactant salt by forming a chelation complex with the molecule 
or ion. Due largely to the solubility of the complexing agent in the 
reaction solvent, the resulting complex is also soluble in the reaction 
solvent. Such complex formation can be exemplified by envisioning 
formation of a chelate, as known in the art, comprising a molecule of the 
complexing agent (serving as a chelating agent) interacting with a 
molecule or ion of the reactant salt in a non-covalent way (i.e., by 
dative bonding) so as to form a coordination compound. In such a 
coordination compound, a molecule or ion of the reactant salt is attached 
by multiple coordination links to two or more usually non-metal atoms in 
the complexing-agent molecule. Complexing agents offering two groups for 
attachment to the ion are termed "bidentate;" complexing agents offering 
three groups are termed "tridentate," and so on. The chemical groups on 
the complexing agent that participate in bonding of the reactant salt are 
typically electron-donors. Complexing agents are also termed "ligands" in 
the art. 
As can be surmised from the foregoing, since molecules of complexing agents 
typically have bonding groups that are electron donors, the regions of the 
corresponding molecules or ions from the reactant salt that become bonded 
to such complexing agents are electron acceptors. For example, 
reactant-salt ions typically are cationic, and can be actual polyatomic or 
monoatomic cations. It is also possible for molecules or ions of the 
reactant salt(s) to interact with the complexing agent by other bonding 
mechanisms such as hydrogen bonding. 
The complexing agent can also interact with a reactant salt in other ways 
to facilitate dissolution of the reactant salt. For example, a complexing 
agent may interact with non-polar regions of ions or molecules of reactant 
salts by, for example, "hydrophobic" bonds. 
The bonding of an ion or molecule of the reactant salt to the complexing 
agent must not be so strong that, during the crystallite-forming reaction, 
the ion or molecule cannot dissociate from the complexing agent. Release 
of the reactant-salt ion or molecule from the complexing-agent molecule to 
form the calcium carbonate product must be energetically favorable. 
Especially preferred complexing agents are any of various crown ethers 
(i.e., any of various cyclic polyethers in which the ether groups are 
connected by methylene or silicon linkages and the ether oxygen atoms 
serve as electron donors). Representative crown ethers include, but are 
not limited to, 12-crown-4, 15-crown-5, 18-crown-6, 
dicyclohexyl-18-crown-6, and dibenzo-18-crown-6. Each crown ether binds a 
particular range of cations, depending upon the size of the central cavity 
of the crown ether molecule. Other possible complexing agents are 
discussed in U.S. Pat. No. 5,545,394, incorporated herein by reference. 
Other cyclic and acyclic polydentate complexing agents can be used, 
including, but not limited to, crown ether analogs containing other donor 
atoms in addition to or in place of oxygen atoms, such as 
1,4,7,10-tetraazacyclododecane ("cyclen"), 
1,4,8,11-tetraazacyclotetradecane ("cyclam"), and 
1,4,7,10,13,16-hexathiacyclooctadecane; and acyclic chelating agents such 
as tris2-2-methoxyethoxy)ethyl!amine, poly(ethylene glycols), and glymes. 
The maximal amount of complexing agent to employ in a desired reaction 
system would be, for economic reasons, no greater than a stoichiometric 
amount relative to the amount of the corresponding reactant salt. Of 
course, if the complexing agent works "catalytically," substantially less 
than a stoichiometric amount would suffice. 
In any event, a person of ordinary skill in the relevant art would be 
familiar with various complexing agents and how to go about selecting an 
appropriate complexing agent for a particular reactant salt and reaction 
solvent. Many candidate complexing agents are commercially available and 
can be tested for efficacy in a given reaction by a simple test-tube 
experiment. I.e., bench-top experiments to test the efficacy of a 
particular complexing agent are within the skill of persons of ordinary 
skill in the relevant art. 
It is also comprehended that many complexing agents, such as (but not 
limited to) crown ethers, can be made more soluble in certain hydrophobic 
solvents by chemically attaching lipophilic moieties to molecules of the 
agents. 
As stated above, reactant salts for forming calcium carbonate according to 
the present invention are normally soluble in water. Reaction solvents for 
use in reaction systems according to the present invention include any of 
various organic solvents that are less polar than water, particularly 
relatively non-polar organic solvents. Such reaction solvents include 
hydrophobic solvents and solvents that have some degree of hydrophilicity 
(normally less than water), and can comprise mixtures of organic solvents 
including such mixtures with water. 
Representative reaction solvents, not intended to be limiting in any way, 
include polar aprotic solvents such as dimethylsulfoxide (DMSO) and 
dimethylformamide (DMF); ethereal solvents such as tetrahydrofuran (THF) 
and diethyl ether; alkanes, olefins, alkyl halides, alcohols, and ketones 
of up to 20 carbons; and aromatic, heteroaromatic, and aryl halide 
solvents of up to 20 carbons such as toluene, nitrobenzene, pyridine, and 
quinoline. These specific solvents, representing various types of organic 
solvents, indicate that any of a wide variety of organic solvents can be 
utilized, and that useful solvents are not limited to a particular class 
of solvents. 
Since the reaction solvent is preferably a liquid under reaction 
conditions, this places a limit on the number of carbons, for example, 
molecules of the reaction solvent can have. Solvent compounds having a 
greater number of carbon atoms (greater than about 20) tend either not to 
be liquids or to be too viscous under reaction conditions to be of 
practical utility. 
Choosing a reaction solvent can be somewhat empirical. Basically, if a 
reactant salt cannot be made to dissolve in the reaction solvent, even 
after attempting to facilitate dissolution using any of various complexing 
agents, a different reaction solvent should be selected. Sometimes, 
difficulties with a reaction solvent can be solved by simply using a 
different complexing agent. If dissolution of the reactant salt is too 
slow, agitation can be helpful, including use of an ultrasonicator. 
The reaction system can include a gel support. Representative gels that are 
relatively polar include, but are not limited to, polyvinylacetate (PVAc) 
and poly(vinylalcohol) (PVA). In the usual instance where the reaction 
solvent is non-polar, any of various non-polar gels can be used, including 
any of various solvent-swollen organic polymer gels such as, but not 
limited to, poly(ethylene) gel, poly(styrene) gel, and poly(vinylchloride) 
(PVC) gel. For example, dissolution of 7-9% (w/w) of poly(vinylchloride) 
in DMSO at elevated temperature (ca. 80.degree. C.), followed by cooling 
to room temperature, affords a suitable solvent-swollen polymer gel. A 
comparable gel is obtained with ca. 18% (w/w) of poly(vinylchloride) in 
DMF. A gel can facilitate the formation of large crystals. Also, use of a 
gel can have particular utility in two-phase reactions (i.e., reactions 
involving one solution layered atop another wherein the reaction occurs at 
the layer interface) according to the present invention, wherein the gel 
can serve to slow the rate of reaction and can simplify setting up the 
phases prior to onset of the reaction. 
Inducing formation of the calcium carbonate product in a reaction system 
according to the present invention can be, and usually is, spontaneous. 
However, crystallization can be triggered by introducing a seed crystal or 
other nucleation aid to the system. A variety of conventional nucleation 
aids are available. Other nucleation aids include anion and cation 
exchange resins. 
Other methods of inducing crystal formation include thermal shock, physical 
shock, and methods that achieve at least localized supersaturation. 
"Double-jet precipitation" has also been used successfully, wherein first 
and second solutions of reactant salts are added simultaneously to a 
stirred crystallizer. 
The products of reactions according to the present invention are 
crystalline forms (i.e., "crystallites") of calcium carbonate. The 
crystallites can comprise an assemblage of individual calcium carbonate 
crystals that are microscopic in size. Generally, the faster the reaction, 
the smaller the crystals of the product. 
The calcium carbonate crystallite products are not necessarily comprised of 
crystals larger than products of corresponding reactions performed 
according to the prior art. Rather, calcium carbonate crystallites formed 
according to the present invention comprise crystals that exhibit an 
altered habit and/or morphology compared to crystals formed according to 
the prior art. In the case of reactions according to the present invention 
forming calcium carbonate products consisting of smaller crystals, such 
crystallites can have unusual physical properties compared to crystallites 
consisting of larger crystals. 
Preferred reactant salts capable of forming calcium carbonate products 
according to the present invention include, but are not limited to, the 
following: 
Representative Calcium Sources 
Calcium fluoride (CaF.sub.2) 
Calcium chloride (CaCl.sub.2) 
Calcium bromide (CaBr.sub.2) 
Calcium iodide (CaI.sub.2) 
Calcium perchlorate (Ca(ClO.sub.4).sub.2) 
Calcium tetrafluoroborate (Ca(BF.sub.4).sub.2) 
Calcium hydroxide (Ca(OH).sub.2) 
Calcium nitrate (Ca(NO.sub.3).sub.2) 
Calcium sulfate (CaSo.sub.4) 
Calcium chlorate (Ca(ClO.sub.3).sub.2) 
Calcium bromate (Ca(BrO.sub.3).sub.2) 
Calcium iodate (Ca(IO.sub.3).sub.2) 
Calcium salts of monobasic acids: (RCO.sub.2).sub.2 Ca, 
wherein RCO.sub.2 =acetate, propanoate, butyrate, valerate, lactate, 
benzoate, salicylate, cinnamate, laurate, linoleate, oleate, palmate, 
stearate, etc. 
Calcium salts of dibasic acids, 
e.g., oxalate, fumarate, maleate, malonate, succinate, tartrate, etc. 
Calcium 2,4-pentanedionate (Ca(CH.sub.3 COCHCOCH.sub.3).sub.2) 
Calcium hexafluoro-2,4-pentanedionate (Ca(CF.sub.3 COFHCOCF.sub.3).sub.2) 
Representative Carbonate Sources 
M.sub.2 CO.sub.3 (M=Li, Na, K, Rb, Cs, NH.sub.4) 
MM'CO.sub.3 (M, M'=Li, Na, K, Rb, Cs, NH.sub.4, 
wherein M and M' are different) 
MHCO.sub.3 (M=Li, Na, K, Rb, Cs, NH.sub.4) 
CO.sub.2 +MOH (M=Li, Na, K, Rb, Cs, NH.sub.4) 
Any reactant salt can be either anhydrous or any of the various hydrates 
thereof. 
The following examples are provided: 
EXAMPLES 1-250 
Although calcium chloride displays appreciable solubility in methanol 
(Hooper et al., in Pamplin (ed.), Crystal Growth, 2d ed., p.395, Pergamon, 
New York, 1980), sodium bicarbonate is virtually insoluble in this 
solvent. However, sodium bicarbonate is readily solubilized in methanol by 
one equivalent of 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6), 
which efficiently chelates sodium ion (Li et al., J. Am. Chem. Soc. 
116:3087-3096, 1994), and 0.13M solutions in methanol are easily obtained 
in this way. 
These examples constitute an investigation into the production of novel 
calcium carbonate morphologies by solvent-solvent interdiffusion. 
For each of examples 1-125, 10 mL of a methanolic sodium 
bicarbonate/18-crown-6 stock solution (0.13M in each component) was placed 
in a 30-mL glass test tube (pre-soaked in a 0.5M solution of EDTA for 12 
hours to eliminate any metal ion contamination, then rinsed three times 
with deionized water and dried). In each tube, a glass-fiber filter paper 
(2.5 cm diameter; Whatman) was carefully placed on the surface of the 
solution Five mL of pure methanol was layered on the filter paper, then a 
second filter paper was placed on the surface of the methanol. Finally, 10 
mL of a 0.13-0.15M solution of CaCl.sub.2 in methanol was layered on the 
second filter paper. (Omission of the reaction-solvent layer (i.e., in 
this instance, the layer of methanol between the filter papers) can result 
in some instantaneous crystallization at the solution/solution interface.) 
Each tube was sealed with a latex septum and waterproof tape, then 
incubated at a constant temperature (8.degree., 21.degree., 38.degree., 
50.degree., or 60.degree. C.) for a specific reaction time (4, 12, 20, 28, 
or 36 days). To ensure reproducibility, five separate tubes were prepared 
for each combination of temperature and reaction time, yielding a total of 
125 tubes. 
For controls (Examples 126-250), a set of similar reactions were run in 
aqueous solution (i.e., no methanol or complexing agent). A total of 125 
control tubes were run, with five tubes for each combination of 
temperature and reaction time. 
After the respective incubation periods, precipitated calcium carbonate was 
isolated from each tube by filtration on 0.05-.mu.m nylon filters, dried, 
and analyzed by X-ray powder diffraction (to assay phase) and scanning 
electron microscopy (to ascertain crystal habit). Energy-dispersive X-ray 
(EDX) analysis was also performed to probe for any crystal contamination 
by reactants. Selected Examples were also assayed by transmission electron 
microscopy (TEM) with selected area diffraction. 
With respect to the controls (Examples 126-250), crystallization of calcium 
carbonate from aqueous solution at higher temperatures yielded calcite, 
generally as well-formed rhombohedral crystals and needles (FIG. 1). 
Longer reaction times at lower temperatures produced somewhat truncated 
analogs of rhombohedral and needle habits. At the highest temperature 
studied (60.degree. C.), traces of aragonite were also observed. 
With respect to Examples 1-125, crystallization from methanol at lower 
temperatures (8.degree. and 21.degree. C.) for relatively short periods of 
time (4 and 12 days) produced mostly calcite (FIG. 2), as verified by 
X-ray powder diffraction and TEM with selected area diffraction. However, 
in contrast to the well-formed crystals obtained in the corresponding 
controls, crystallization from methanol generally produced roughly 
spherical aggregates of much smaller and more poorly formed rhombohedral 
crystallites (FIG. 3). Higher temperatures and/or longer reaction times 
resulted in the selective formation of the vaterite phase generally in the 
form of spherical aggregates (FIG. 4; closeup shown in FIG. 5) displaying 
much lower crystallinity (as evidenced by broad X-ray diffraction lines) 
than the calcite spheres. After long growth periods (e.g., 28days) at 
21.degree. C., a completely new fibrous habit was seen (FIG. 6). Growth at 
8.degree. C., which produced pure calcite after short reaction times, 
produced a ca. 1:1 mixture of calcite and vaterite after 20 days, and pure 
vaterite after a 36-day growth period, all as verified using X-ray powder 
diffraction. Growth at 38.degree. C. produced pure vaterite within 4 days 
and thereafter. 
Formation of vaterite in Examples 1-125 appeared to arise from 
transformation of the initially formed calcite to vaterite rather than by 
initial formation of a pulse of calcite followed by slower precipitation 
of vaterite. Thus, for example, growth at 21.degree. C. for 12 days 
produced an average of 0.036 g of pure calcite, while growth for 36 days 
produced an average of 0.047 g of pure vaterite. 
Also with respect to Examples 1-125, crystallization from methanol at 
50.degree. C. produced both vaterite, again as spherical aggregates, and 
aragonite in needle-like habits. At these higher temperatures, aragonite 
was observed even at the shorter reaction periods, and phase 
interconversion was not clearly indicated in these preparations. 
The substantial reduction in calcite crystallite size observed after 
reaction in methanol probably represents, inter alia, a proportionate 
increase in nucleation versus growth rate in this non-aqueous solvent. 
This may be due to the lower viscosity of methanol versus water (affording 
higher diffusion rates) and the anticipated higher degree of 
supersaturation achieved in methanol (an intrinsically poorer solvent for 
these materials). With respect to the formation of vaterite at the expense 
of calcite, published CaCO.sub.3 phase diagrams (Albright, Amer. Miner. 
56:620-624, 1971) are somewhat sketchy about the stability regime for 
vaterite, and often omit this phase entirely (Liu et al., Amer. Miner. 
75:801-806, 1990; Alam et al., J. Am Ceram. Soc. 73:733-735, 1990; 
Carlson, Amer. Miner. 65:1252-1262, 1980; Salje et al., Contrib. Mineral. 
Petrol. 55:55-67, 1976; Goldsmith et al., Am. J. Sci. 167A:160-190, 1969; 
Crawford et al., Science 144:1569-1570, 1964; Bell et al., Carnegie Inst. 
Washington Yearb. 63:177-179, 1963/1964; Simmons et al., Science 
139:1197-1198, 1963; Clark, Amer. Miner. 42:564-565, 1957; Jamieson, J. 
Geol. 65:334-343, 1957; MacDonald, J. Amer. Miner. 41:744-751, 1956;and 
Jamieson, J. Chem. Phys. 21:1385-1390, 1953). Nevertheless, calcite is the 
thermodynamically favored bulk phase under ambient conditions (i.e., 1 atm 
pressure, near room temperature). 
Therefore, surface effects (e.g., solvent-surface and/or crown 
ether-surface interactions) appear to be responsible for vaterite 
formation in the foregoing Examples, with very small vaterite crystallite 
size allowing surface-energy terms to overcome the intrinsic bulk 
thermodynamic stability of calcite. This conversion is aided by the 
initial formation of microcrystalline calcite; macroscopic calcite 
crystals, in contrast, in which bulk energy terms overwhelm surface energy 
terms, do not convert to vaterite even after prolonged contact with 
methanol/18-crown-6. 
The foregoing studies highlight the ability of complexation-mediated 
crystallization to exploit simple solvent effects for the alteration of 
the crystal habit or morphology of calcium carbonate. These observations 
bear direct relevance to biomineralization. The foregoing studies 
demonstrate that even a comparatively simple change in solvent from water 
to methanol can exert a dramatic influence on calcium carbonate phase 
preference. 
Whereas the present invention has been described in connection with 
preferred embodiments and numerous examples, it will be understood that 
the invention is not limited to those embodiments or examples. On the 
contrary, the invention is intended to encompass all alternatives, 
modifications, and equivalents as may be included within the spirit and 
scope of the invention as defined by the appended claims.