Di- tert-butylphosphate Derived Thermolabile Calcium Organophosphates: Precursors for Ca(H2PO4)2, Ca(HPO4), α-/β-Ca(PO3)2, and Nanocrystalline Ca10(PO4)6(OH)2

Article abstract of DOI:10.1021/acs.inorgchem.0c01591

Thermally and hydrolytically unstable di-tert-butyl phosphate (dtbp-H) has been used as synthon to prepare discrete and polymeric calcium phosphates that are convenient single-source precursors for a range of calcium phosphate ceramic biomaterials. The reactivity of dtbp-H toward two different calcium sources has been found to vary significantly, e.g., the reaction of Ca(OMe)2 with dtbp-H in a 1:6 molar ratio in petroleum ether forms a mononuclear calcium hexa-phosphate complex [Ca(dtbp)2(dtbp-H)4] (1), whereas the change of calcium source to CaH2, in a 1:2 molar ratio under otherwise similar reaction conditions, yields the calcium phosphate polymer, [Ca(μ-dtbp)2(H2O)2·H2O]n(2). Compounds 1 and 2 have been extensively characterized by various spectroscopic and analytical techniques. The solid-state structures of both 1 and 2 have been determined by single-crystal X-ray diffraction studies. In discrete molecule 1, the central calcium ion is surrounded by two anionic dtbp and four neutral dtbp-H ligands in an octahedral coordination environment. Compound 2 is a one-dimensional polymer in which adjacent calcium ions are connected through double dtbp bridges. Solid-state thermolysis of bulk 1 in air leads to the exclusive formation of calcium metaphosphate β-Ca(PO3)2 in the entire temperature range of 400-800 °C. Thermal decomposition of polymer 2, however, can be fine-tuned to produce either α-Ca(PO3)2 or β-Ca(PO3)2 depending on the thermolysis conditions employed. Although the sample sintered at 600 °C produces exclusively α-form of Ca(PO3)2, the sample annealed at 800 °C or above produces β-form. Both α- and β-forms can also be successively formed one after other by a slow heating of a freshly prepared 2 on the powder diffractometer sample holder. Additional forms of ceramic phosphates have been prepared by solvothermal conditions because of the highly labile nature of the tert-butoxy groups of dtbp in 1 and 2. Solution decomposition of either 1 or 2 in boiling toluene at 140 °C in a sealed tube produces calcium dihydrogen phosphate [Ca(H2PO4)2·H2O] as the only product in the form of single crystals. Solution thermolysis of 2 in protic solvents such as water and methanol can be biased to produce other calcium phosphate biomaterials such as hydroxyapatite [Ca10(PO4)6(OH)2]and calcium monohydrogen phosphate [Ca(HPO4)] in the presence of additional calcium precursors such as CaO and Ca(OMe)2, respectively.

Full text of DOI:10.1021/acs.inorgchem.0c01591

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Di-tert-butylphosphate Derived Thermolabile Calcium
Organophosphates: Precursors for Ca(H2PO4)2, Ca(HPO4), α‑/β-
Ca(PO3)2, and Nanocrystalline Ca10(PO4)6(OH)2
Sonam Verma and Ramaswamy Murugavel*
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ABSTRACT: Thermally and hydrolytically unstable di-tert-butyl
phosphate (dtbp-H) has been used as synthon to prepare discrete
and polymeric calcium phosphates that are convenient single-source
precursors for a range of calcium phosphate ceramic biomaterials.
The reactivity of dtbp-H toward two different calcium sources has
been found to vary significantly, e.g., the reaction of Ca(OMe)2 with
dtbp-H in a 1:6 molar ratio in petroleum ether forms a mononuclear
calcium hexa-phosphate complex [Ca(dtbp)2(dtbp-H)4] (1),
whereas the change of calcium source to CaH2, in a 1:2 molar
ratio under otherwise similar reaction conditions, yields the calcium
phosphate polymer, [Ca(μ-dtbp)2(H2O)2·H2O]n(2). Compounds 1
and 2 have been extensively characterized by various spectroscopic
and analytical techniques. The solid-state structures of both 1 and 2 have been determined by single-crystal X-ray diffraction studies.
In discrete molecule 1, the central calcium ion is surrounded by two anionic dtbp and four neutral dtbp-H ligands in an octahedral
coordination environment. Compound 2 is a one-dimensional polymer in which adjacent calcium ions are connected through
double dtbp bridges. Solid-state thermolysis of bulk 1 in air leads to the exclusive formation of calcium metaphosphate β-Ca(PO3)2
in the entire temperature range of 400−800 °C. Thermal decomposition of polymer 2, however, can be fine-tuned to produce either
α-Ca(PO3)2 or β-Ca(PO3)2 depending on the thermolysis conditions employed. Although the sample sintered at 600 °C produces
exclusively α-form of Ca(PO3)2, the sample annealed at 800 °C or above produces β-form. Both α- and β-forms can also be
successively formed one after other by a slow heating of a freshly prepared 2 on the powder diffractometer sample holder. Additional
forms of ceramic phosphates have been prepared by solvothermal conditions because of the highly labile nature of the tert-butoxy
groups of dtbp in 1 and 2. Solution decomposition of either 1 or 2 in boiling toluene at 140 °C in a sealed tube produces calcium
dihydrogen phosphate [Ca(H2PO4)2·H2O] as the only product in the form of single crystals. Solution thermolysis of 2 in protic
solvents such as water and methanol can be biased to produce other calcium phosphate biomaterials such as hydroxyapatite
[Ca10(PO4)6(OH)2]and calcium monohydrogen phosphate [Ca(HPO4)] in the presence of additional calcium precursors such as
CaO and Ca(OMe)2, respectively.
stable and biocompatibile and exhibit bone regeneration and
tissue repairing properties.8−11 However, synthetic HA is not
as advantageous for bone substitution as natural HA because of
the modulus mismatch and limited bioresorption. Therefore,
combinations of β-Ca3(PO4)2 (tricalcium phosphate, β-TCP)
and HA are commonly used as bioactive implants in human
bone surgery.9,12−18 TCP and HA can be synthesized by using
various CP precursors such as Ca(H2PO4)2·H2O and Ca-
(HPO4).19,20 Alternative sources of calcium phosphates such
INTRODUCTION
■
Sustained interest in the chemistry of calcium phosphates
(CPs), which exist in a number of compositional variations,
can be easily traced to diverse applications of these materials in
a number of fields (for a nonexhaustive list of CPs, see Table
S1). For instance, calcium phosphates are used as bone
substitutes in biomedical industry because of their biocompat-
ibility, low density, and redox inactivity, apart from their
compositional similarity with the mineral phases of bone.1−4
Materials such as polymers, metals, and carbon-based
ceramics5 used in clinical applications suffer from their low
biocompatibility and poor adhesion to tissues.6 These issues
are often resolved by calcium phosphate-based ceramics, which
are abundant in native human bone and have begun to emerge
as suitable biomaterials.7,8 These (bio)materials, such as
Ca10(PO4)6(OH)2 (hydroxyapatite, HA), are biologically
Received: May 31, 2020
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Scheme 1. Synthesis of Calcium Di-tert-butylphosphates 1 and 2
as Ca(PO3)2 have also shown potential applications in bone
substitution because of their very high bioresorption and
osteoconductivity.21−24 They also find use as drug delivery
systems25−27 and ceramic−polymer composite biomateri-
als.28−30 More recently, research on calcium phosphates and
their coatings has dealt with preventing implant corrosion and
increasing bioactivity,31,32 controlling pore size and improving
mechanical strength,33 and minimizing foreign body re-
sponse.34,35
Human bone is mainly composed of inorganic nanosized
crystalline HA (nHA) and organic collagen fibrils.36,37 The
nHA, a highly crystalline material that exists as rods or needles
(∼40−60 nm length),38 is one of the most significant materials
in human implant and tissue engineering because of its
osteoconductive, osteoinductive, biocompatible, bioactive, and
mechanical properties.39−44 Its ability to quickly fix with
neighboring bones makes nHA a more useful material for bone
repair or artificial bone grafts.45,46 Moreover, the high surface
area of nHA significantly increases osteoblast adhesion on
nanophase compared to micrometer-sized HA ceramic materi-
al.47,48
solution during the course of the reaction. Hence it has been
envisaged that the use of Ca(OMe)2 or CaH2 as alternate
starting materials would produce only MeOH or H2 as
byproducts, respectively. Further, these precursors would also
offer the possibility of carrying out reactions in nonprotic
solvents.
Accordingly, the reaction of calcium methoxide Ca(OMe)2
with dtbp-H was carried out in a 1:2 ratio by stirring the
reactants in petroleum ether under ambient conditions. This
reaction proceeded smoothly and produced mononuclear
calcium hexaphosphate complex [Ca(dtbp)2(dtbp-H)4] (1)
as the major product (42%); however, small quantities of
[Ca(μ-dtbp)2(H2O)2·H2O]n (2) (16%) were also produced as
the second minor product (Scheme 1). These two can be
separated from one another by exploiting their solubility
difference. Formation of 1 as the major product is surprising
because only 2 equiv. of dtbp-H was originally used in the
reaction. The formation of 2, however, was suppressed and the
yield of 1 significantly increased to 68% by employing 6 equiv.
of dtbp-H for 1 equiv. of Ca(OMe)2. In complex 1, among the
six phosphate ligands coordinated to the metal, two are anionic
(dtbp−), whereas the other four are neutral (dtbp-H) ligands
coordinated through the phosphoryl oxygen.
Exclusive formation of calcium phosphate polymer 2 was
subsequently achieved by changing the starting material from
calcium methoxide to calcium hydride. Thus, stirring of a
slurry of CaH2 and 2 equiv. of dtbp-H in petroleum ether for
24 h produced a white precipitate, which on crystallization
from commercial grade methanol yielded single crystals of
[Ca(μ-dtbp)2(H2O)2·H2O]n (2) as the only product in 72%
yield.
Research work carried out over last two decades by us49−54
and Tilley and co-workers55−58 has established the power of di-
tert-butylphosphate ((tBuO)2PO2H; dtbp-H) to prepare
several organic soluble p-block and transition-metal molecular
phosphates that undergo clean thermolysis at temperatures
below 200−350 °C to produce corresponding metal phosphate
ceramics.50−53,55−57 However, these advantages of di-tert-
butylphosphate within the vast area of calcium phosphate
̀
chemistry outlined above, vis-a-vis the use of phosphoric acid
or its sodium salts as the source of phosphate anions, has not
yet been explored. Hence, the primary motivation for the
present work is to take advantage of the solubility of dtbp-H in
organic solvents to produce CP materials in nonaqueous
medium. In line with this objective, we have explored in the
present study the reactivity of calcium precursors such as
Ca(OMe)2 and CaH2 with dtbp-H for the first time to produce
discrete and 1D polymeric calcium organophosphates. Solid-
state or solution decomposition of these species produces a
large number of ceramic phases under relatively milder
conditions. The details are described in this contribution.
Spectral Characterization of 1 and 2. Calcium
phosphates 1 and 2 have been characterized by both
spectroscopic (IR, NMR, and ESI-MS) and analytical methods.
Their molecular structures have also been established by
single-crystal X-ray diffraction studies. Mononuclear com-
pound 1 was found to be more freely soluble in organic
solvents than the polymer 2, which was found to be soluble
only in solvents such as methanol. The broad stretching band
observed in the range 3600−3200 cm−1 attributed to hydroxyl
group of P−OH and H2O groups of 1 and 2 in the FT-IR
spectrum. The bands observed in the range 3000−2900 cm−1
of 1 and 2 correspond to the C−H stretching of the alkyl
groups. The absorption bands appearing at 1217, 1108, and
1087 for 1 and 1217, 1182, and 1040 cm−1 for 2 are assigned
to PO and P−O−M stretching (antisymmetric and
symmetric) vibrations, respectively (Figure S1).
RESULTS AND DISCUSSION
■
Synthesis. In an effort to produce organic soluble calcium
compounds of dtbp-H in varying stoichiometries, we initially
performed reactions of commonly available calcium starting
materials such as its acetate, chloride, and carbonate with
either dtbp-H or its potassium salt dtbp-K. Although these
reactions led to the formation of different types of calcium-
dtbp complexes, several additional byproducts also formed,
probably due to the release of acetic acid or HCl to the
The 1H NMR spectra obtained for 1 and 2 (Figures S2 and
S3) are consistent with their molecular structures obtained
from single-crystal X-ray diffraction studies described below. In
1
the H NMR spectrum of 1, the singlet appearing at δ 1.44
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Figure 1. (a) Molecular and (b) core structure of 1 (H atoms have been omitted for clarity). Selected bond lengths and angles: Ca1−O8 =
2.322(3) Å, Ca1−O3 = 2.334(3) Å, and Ca1−O9 = 2.346(3) Å and ∠O9−Ca1−O3 = 89.7(1)°, ∠O3−Ca1−O9 = 90.2(1)°, ∠O8−Ca1−O3
87.9(1)°, and ∠O8−Ca1−O9 90.8(1)°.
Figure 2. (a) Structure of polymer 2. (b) Arrangement of the polymeric chain in the lattice (H atoms have been omitted for clarity). Selected bond
lengths and angles: Ca1−O5 = 2.278(2), Ca1−O1 = 2.294(2), Ca1−O9 = 2.434(2), and Ca1−O10 = 2.346(2) Å and ∠O1Ca1O5 = 90.4(1)°,
∠O3Ca1O8 = 82.7(1)°, ∠O10Ca1O5 = 90.9(1)°, and ∠O5Ca1O9) = 95.2(1)°. (c) Hydrogen bonding interactions.
ppm corresponds to the methyl proton of tBu group. Similarly,
the singlet for the methyl and water protons of 2 resonate at δ
1.43 ppm and at δ 4.91 ppm, respectively. Further evidence for
the isolation of 1 and 2 in pure form is evident through the
presence of a single resonance in their 31P NMR spectrum at δ
−9.3 ppm and −8.33 ppm, respectively (Figures S4 and S5).
Compounds 1 and 2 have further been characterized by 13C
NMR spectroscopy, which is also consistent with the molecular
structures shown in Scheme 1 (Figures S6 and S7).
Calcium hexaphosphate 1 was found to be stable under
electrospray ionization mass spectrometry (ESI-MS) con-
ditions, yielding a signal for the [M + K]+ ion at m/z 1337 with
the expected isotopic pattern (Figure S8). Similarly, mass
spectrum of 2 exhibits peaks for the monomeric species plus
lithium ion [(Ca(dtbp)2(H2O)2)+Li]+ at m/z 501, whose
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Figure 3. TGA of compounds 1 (left) and 2 (right) along with the sequence of decomposition and assignment of each weight loss.
simulated and experimental isotopic pattern are in good
agreement (Figure S9).
Molecular Structure of [Ca(dtbp)2(dtbp-H)4] (1).
Colorless single crystals of 1 suitable for X-ray diffraction
studies were obtained from petroleum ether solution under
ambient conditions through slow evaporation of the solvent
over 4 days. Diffraction studies reveal that 1 is a
resulting in the composition of [Ca(μ-dtbp)2(H2O)2·H2O]n
for 2. The lattice water molecule forms two hydrogen bonds
with coordinated water molecules (O10−H10···O11 2.853(3)
Å and 129.8°; O10−H10′···O11 2.770(3) Å and 173.0°) and
two H-bonds with phosphate ligands (O11−H11···O3
2.872(3) Å and 139.2°; O11−H11···O8 2.831(3) Å and
167.9°). Further, H-bonding is also observed between the
coordinated water molecule and the phosphate ligand (O9−
H9B···O6 = 2.896(3)Å, 154.5°), all contributing to the
stability of the polymer (Figure 2c).
Thermogravimetric Analysis. One of the main reasons
why the tert-butyl diester of phosphoric acid has gained a lot of
prominence in materials chemistry is due to the fact that
M(dtbp)n systems cleanly eliminate iso-butene through β-
hydride elimination to produce [M(O2P(OH)2)]n, which itself
being metastable would further eliminate water molecules to
produce metal phosphate materials.50−53 To test the
applicability of this approach for calcium phosphates 1 and
2, their TGA analysis was carried out under a flow of N2 at a
heating rate of 10 °C/min (Figure 3).
Calcium hexaphosphate [Ca(dtbp)2(dtbp-H)4] (1) under-
goes a two-stage thermal decomposition as shown in Figure 3
(left). The first weight loss occurring in the temperature range
90−120 °C corresponds to the removal 12 molecules of iso-
butene gas from dtbp and dtbp-H ligands, amounting to a loss
of 51.7% of the mass, to produce [Ca(H2PO4)2(H3PO4)4].
This species on further heating loses about 8 equiv. of water
molecules to produce Ca(PO3)2·P4O10 composite, which
amounts to 37.1% of the ceramic yield.
Compound 2 with a metal to phosphate ratio of 1:2 shows a
straightforward thermal decomposition behavior (Figure 3
(right)). The first weight loss that occurs in the temperature
range 40−80 °C, corresponding to a weight loss of ∼10%, is
due to removal of lattice (one) and coordinated water (two)
molecules in two stages leaving Ca(dtbp)2 at this stage in the
thermal balance. Increasing the temperature to 100 °C leads to
the rapid loss of isobutene gas (weight loss ∼43.8%) from the
tert-butoxy groups to form Ca(H2PO4)2. Upon increasing the
temperature further, the P−OH groups condense through loss
of water molecules (in the range of 200−400 °C) to form
ceramic calcium phosphate Ca(PO3)2 in ∼39% ceramic yield.
A bulk thermolysis of both 1 and 2 carried out under a variety
of decomposition conditions throw further light into the
phases produced and transformations involved.
̅
centrosymmetric molecule crystallizing in triclinic P1 space
group with one-half of the molecule occupying the asymmetric
part of the unit cell. The molecular structure of 1 is composed
of one calcium ion and six di-tert-butyl phosphate ligands
(Figure 1a). Coordination around the calcium ion is provided
by six oxygen atoms from six di-tert-butyl phosphate ligands,
completing a near ideal octahedral coordination geometry
around the divalent calcium (Figure 1b). The fact that this
molecule is neutral and that the dtbp ligand is monoanionic
leads to the conclusion that out of six phosphate ligands, only
two are deprotonated, whereas the other four are coordinated
to the metal in the neutral form. Accordingly, the calcium to
monoanionic phosphate distance is marginally shorter (Ca1−
O8 = 2.322(3) Å) than the other calcium−neutral phosphate
bonds (Ca1−O3 2.334(3) and Ca1−O9 2.346(3) Å).
Consequently, strong intramolecular H-bonding occurs
between the uncoordinated P−OH group of neutral phosphate
and the phosphoryl oxygen of monoanionic phosphate (O11−
H11···O6 2.43(3) Å and 166.1°), contributing to further
stability of the complex in the solid state.
Molecular Structure of [Ca(μ-dtbp)2(H2O)2·H2O]n (2).
Although compound 2 is synthesized from a petroleum ether
solution, single crystals of 2 could be obtained only from a
methanol solution at 25 °C after 4 days. The crystallization
from wet methanol under ambient conditions also serves as the
source of coordinated and lattice water molecules found in the
structure of 2 (Figure 2a−c). X-ray diffraction studies reveal
that compound 2 is a one-dimensional polymer crystallizing in
monoclinic P21/n space group, and polymer 2 is composed of
a continuum of Ca2P2O4 single-4-rings (spiro) that are
connected at the calcium centers (Figure 2). In other words,
the adjacent calcium ions of the polymeric chain are connected
through double dtbp bridges on either side producing a rod-
like polymer shown in Figure 2a. Apart from being bound by
two bridging dtbp ligands, two water molecules are
coordinated to each calcium ion in a trans fashion to complete
the octahedral geometry around calcium ion (Figure 2b). A
lattice water molecule is also found in each repeating unit,
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Bulk Solid-State Thermolysis. Thermal decomposition of
1 was carried out in steps by heating the sample at 200, 400,
600, and 800 °C in a muffle furnace. The ceramic material
obtained after each decomposition was analyzed by powder X-
ray diffraction (PXRD) studies (Figure 4). Consistent with the
Figure 5. Stack plot of PXRD pattern of as-synthesized 2 along with
the decomposition products obtained after bulk pyrolysis at 200, 400,
600, 700, and 800 °C; the ICSD data for calcium phosphate ceramic
materials for α-and β-Ca(PO3)2 are also shown.
Figure 4. PXRD pattern of as-synthesized 1 and the decomposition
products obtained after pyrolysis at 200, 400, 600, and 800 °C, along
with the ICSD data for β-Ca(PO3)2.
are pictorially shown in Figure 6. It is interesting to note that if
the sample is heated at 20 °C/min in the temperature range
25−800 °C, with a hold of 2 min at each measurement, only β-
Ca(PO3)2 is obtained as the final ceramic product (Figure 6;
left). Conversely, if the same sample is heated at a slower rate
(10 °C/min) and the sample was held at each measurement
temperature for 30 min, the final ceramic product obtained was
α-Ca(PO3)2 (Figure 6; right). Thus, it turns out that the final
ceramic material formed during thermolysis can be influenced
to either of the two crystalline phases of calcium
metaphosphate (α or β) just by tuning the decomposition
temperature and/or the heating rate.
Solvothermal Decomposition Studies. The formation
of Ca(PO3)2 starting from 2 should have preceded via the
formation of Ca(H2PO4)2 as suggested from the TGA (Figure
3 (right)). Although this product forms at around 100 °C, it
readily self-condenses during solid-state thermolysis to
produce the final metaphosphate product. To isolate Ca-
(H2PO4)2, we resorted to milder thermal decomposition in
solution under solvothermal conditions. Accordingly, polymer
2 was dispersed in toluene inside a sealed Pyrex tube and
heated at 140 °C for 2 days in an oven. Cooling the resultant
solution produced single crystals of monocalcium phosphate
monohydrate (MCPM) [Ca(H2PO4)2·H2O], which has been
thoroughly characterized including a bulk purity test by PXRD
studies (Figure S22; left). It should be noted that a new
calcium phosphate cement system was recently formed via
mixing of MCPM and β-TCP as a bone graft material, which
shows good cohesion, compressive strength, and mechanical
properties in fast bone regeneration.61,62
TGA trace, heating the bulk sample of 1 (Figure 4; trace a) to
200 °C leads to marked change in the PXRD where all low-
angle peaks have disappeared with the production of a less
crystalline material (trace b). The sample heated to 400 °C
(trace c) is quite amorphous, although the positions of the
broad peaks correspond to the well-resolved peaks of the
sample heated to even higher temperatures of 600 and 800 °C
(traces d and e, corresponding to calcium metaphosphate β-
Ca(PO3)2) (trace f is from ICSD-60117).
As evident from Figure 5, bulk thermolysis of polymer
[Ca(μ-dtbp)2(H2O)2]n (2) produces more interesting results,
which include a phase transition. The metal−organic polymer
2 (Figure 5; trace a) on heating 200 °C loses the lattice and
coordinated water molecules and iso-butene from tert-butoxy
groups of the phosphate ligands to produce an amorphous
material (trace b). Incidentally the sample heated at 400 °C
also produces a predominantly amorphous material (trace c).
However, when the thermolysis temperature was raised to 600
°C (trace d), the material produces a crystalline XRD pattern
that matches well with the expected diffraction pattern of α-
Ca(PO3)2 (trace e; ICSD-417710). Raising the thermolysis
temperature to 700 °C results in a phase change as well as
partial loss of crystallinity, as can be seen from trace f in Figure
5. The sample again becomes crystalline at 800 °C (trace g),
whose PXRD pattern matches well with that of β-Ca(PO3)2
(trace h; ICSD- 60117). Thus, solid-state thermolysis can be
controlled to yield either amorphous (200−400 °C), α-
Ca(PO3)2 (600 °C), or β-Ca(PO3)2 (>700 °C). The 31P MAS
NMR of samples calcined at 600 and 800 °C (Figures S14;
vide infra) clearly show that these samples correspond to the
composition α-Ca(PO3)2 and β-Ca(PO3)2, respectively.59,60
Production of two different crystalline phases of calcium
metaphosphate during bulk thermolysis prompted further
studies through in situ decomposition of 2 directly on the
sample holder of a powder diffractometer. The results obtained
As precursor compound 2 contains a calcium to phosphate
ratio of 1:2, the ceramic phosphates derived also retain the
same Ca:P ratio (vide supra). Because the biologically relevant
calcium phosphates exhibit other Ca:P compositions, often
with less phosphate and more calcium (Table S1), a solution-
phase cothermolysis was envisaged by adding another calcium
precursor along with 2 during decomposition. For example,
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Figure 6. Variable-temperature PXRD of 2 producing two different phases at two different heating rates: (left) the heating rate was 20 °C/min and
the sample was held at each temperature for 2 min, and the XRD was recorded over 20 min; (right) the heating rate was 10 °C/min and the sample
was held at each temperature for 30 min before the XRD was recorded over 20 min.
Figure 7. (a) SEM image of HA at 100 nm, (b) diffraction pattern of HA crystals, and (c) Bright field HRTEM image of HA and plane assignment
in inset.
mixing 2 with Ca(OMe)2 in a 1:1 ratio in MeOH and
subjecting the resulting solution in a sealed tube to
solvothermal conditions at 150 °C for 2 days produced
dicalcium phosphate Ca(HPO4), which is one of the rare
calcium phosphates that has an M:P ratio of 1:1 (Figure S22;
right). Interestingly, Sheikh et al. have shown that Ca(HPO4)·
2H2O cement grafts transformed to monetite Ca(HPO4)-
based biomaterials and demonstrated complete graft resorption
and more bone formation than brushite.63
Hydrothermal Decomposition Studies. Although solid-
state and solution thermolysis of 2 can be exploited for the
preparation of calcium phosphates Ca(H2PO4)2·H2O, Ca-
(HPO4) and α-/β-Ca(PO3)2, the possibility of employing most
attractive of all CPs, viz. hydroxyapatite (HA), has remained
elusive. This is particularly important because shape, size,
purity, and homogeneity of HA play a crucial role in many of
its applications and functionality. Recent studies have provided
various solutions to produce regular-shaped HA nanosize
structures by using different methods and starting materials.
Hydroxyapatite is generally synthesized by methods such as
wet precipitation, sol−gel approach, solid-state methods,
hydrothermal techniques, multiple emulsion techniques, and
biomimetic deposition.64−72
Inspired by the cothermolysis of 2 with Ca(OMe)2
producing Ca(HPO4), we investigated the cothermolysis of
these two starting materials once again in a 3:7 ratio (which
3−
matches the requirement of HA in terms of Ca2+ and PO4
content), expecting facile formation of HA. However, the
cothermolysis of these two calcium sources, regardless of the
ratio employed, did not produce any HA. However, when CaO
was used as the alternative source along with 2 in the desired
ratio in water, formation of HA takes place under hydro-
thermal conditions under neutral conditions, although the
same product can be obtained even under basic conditions
(pH 10). The crystalline product obtained from solution
displays the typical PXRD pattern of HA (ICSD- 26205), also
revealing the absence of any other CP phases in bulk (Figure
S23). Further, the SEM and TEM images of HA produced by
the present synthetic methodology reveals needle-shape
morphology for the product (length of 50−500 nm and
width of 20−50 nm) (Figure 7a and Figure S25). The selected
area diffraction (SAED pattern) shows diffused pattern, which
further confirms the crystallinity of HA (Figure 7b, c).
Apart from the PXRD studies detailed above, the formation
of all the ceramic materials (CMs) obtained by decomposition
of 1 and 2 have been further confirmed by relevant
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Figure 8. 31P CP-MAS NMR spectra of decomposed products of 2: (a) 2−800 (β-Ca(PO3)2), (b) 2-Ca10(PO4)6(OH)2, (c) 2-Ca(H2PO4)2·H2O,
and (d) 2-Ca(HPO4); comparison with corresponding reported compounds in the insets. For details, see text.
spectroscopic (IR, DR-UV−vis, and 31P CP-MAS NMR),
microscopic (SEM and TEM), and BET surface area
measurement studies. The FT-IR spectra of all CMs are
devoid of C−H stretching vibrations of the alkyl groups in the
range 3000−2800 cm−1, confirming complete and clean loss of
tertiary butyl groups early on in the decomposition process.
The absorption bands appearing at 1190−1020 cm−1 are
assigned to PO and those appearing at 1005−930 cm−1 to
P−O−Ca stretching (antisymmetric and symmetric) vibra-
tions, respectively (Figures S12, S13, and S20).
of all ceramic materials reveal that these condensed-phase
materials have BET surface areas in the range of 8.63−117.12
m2/g (details in Figures S18, S19, and S27).
Mechanistic Insights into Decomposition of [Ca(μ-
dtbp)2(H2O)2·H2O]n (2). The ability of organocalcium
polymer 2 to form a number of inorganic calcium phosphate
phases prompts a mechanistic understanding of the various
transformations. Scheme 2 (along with Scheme S1) summa-
rizes the possible reaction pathways through which these
transformations would have taken place. As shown in Scheme
2, the initial response for a solid-state or solution thermolysis
of polymer 2 is the decomplexation of coordinated water
molecules. Extended thermolysis of the dtbp complex at
temperatures above 100 °C results in facile β-hydride
elimination, producing Ca(H2PO4)2, very much akin to the
formation of Co(H2PO4)2 from Co(dtbp)2.54 The Ca-
(H2PO4)2 thus formed is the central intermediate for all
other transformations that occur through pathways a−c shown
in Scheme 2.
When the thermolysis is carried out in the presence of 1
equiv. of Ca(OMe)2, a facile condensation between Ca(OMe)2
and the intermediate Ca(H2PO4)2 through the elimination of 2
equiv. of methanol (also see Scheme S1). The solution
cothermolysis of 2 with CaO in a 3:7 stoichiometry (path b),
on the other hand, results in a dehydration reaction where each
unit of Ca(H2PO4)2 combines with two equivalents of CaO to
eliminate two equivalents of water to produce the well-known
oxyapatite Ca10(PO4)6(O), which picks up a water molecule
and gets converted to hydroxyapatite, Ca10(PO4)6(OH)2. Path
c in Scheme 2 shows how further heating of Ca(H2PO4)2 in
The31P CP-MAS NMR spectra of a selection of these
ceramic materials (along with the spectra of authentic samples
as inset) are shown in Figure 8 (also see Figure S14).59,60,73−76
The 31P CP-MAS NMR of β-Ca(PO3)2 obtained by
decomposing 2 at 800 °C presents four peaks in the range
−30.39 to −34.97 ppm (Figure 8a), whereas a single resonance
is observed at 3.4 ppm for the nanocrystalline HA (Figure 8b).
Two resonances appear at −3.01 and −7.61 ppm for
Ca(H2PO4)2·H2O obtained by solvothermal treatment of 2
(Figure 8c), whereas one broad unresolved resonance is
observed for Ca(HPO4) appearing in the range δ 5 to −2 ppm
(Figure 8d).
DR UV−vis absorption spectra for all compounds recorded
under ambient conditions exhibit absorption bands in the
range 200−300 nm attributable to n−π* electronic transitions
(Figures S16, S17, and S26). The SEM studies reveal that most
of these materials obtained were micrometer-sized crystals
(Figures S15 and S24a−c), whereas that of hydroxyapatite was
obtained as nanocrystals (Figure 7a and Figure S24d).
Nitrogen adsorption−desorption isotherms measured at 77 K
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the solid-state leads to self-condensation to eliminate 2 equiv.
of water to produce either α- or β-forms of Ca(PO3)2,
depending on the decomposition temperature and heating rate,
as described above. Thus, polymer 2 transforms to Ca-
(H2PO4)2, Ca(H2PO4)2·H2O, Ca(HPO4), Ca10(PO4)6(O),
Ca10(PO4)6(OH)2, and finally Ca(PO3)2, according to reaction
sequences indicated in Scheme 2 and Scheme S1.
Scheme 2. Proposed Mechanism for the Formation of
Various CP Phases from Organocalcium Phosphate
Polymer 2 )
a
CONCLUSIONS
■
We have successfully demonstrated in this contribution the
capability of di-tert-butylphosphate as a starting point for
preparing an organic-soluble calcium organophosphates, [Ca-
(dtbp)2(dtbp-H)4] (1) and [Ca(μ-dtbp)2(H2O)2·H2O]n (2).
Although 1 is a molecular compound with a phosphate excess
construct (Ca:P = 1:6), the 1D polymer 2 has proven to be a
useful thermolabile precursor for the preparation of a variety of
ceramic CPs in an extremely pure form. As summarized in
Scheme 3, decomposition of 2 can be carried out under a
variety of conditions to produce a number of calcium ceramic
phosphates, which are useful biomaterials as themselves or as
their precursors. This study also brings to light the importance
of controlling the rate and temperature of decomposition to
switch between the phases of a given ceramic material. It has
been demonstrated that the α- and β-forms of Ca(PO3)2 can
be selectively prepared by performing bulk thermolysis at 600
and 800 °C, respectively. This selective formation of phases
has also been adequately supported by in situ decomposition
of 2 on a PXRD machine at two different heating rates.
Although rapid heating of the sample leads to exclusive and
clean formation of β-Ca(PO3)2, slow heating leads to the
formation of predominately α-Ca(PO3)2 phase. This work has
further shown that, apart from bulk solid-state thermolysis,
solution thermolysis (both solvo- and hydrothermal) can also
be employed to prepare additional CP phases. Although stand-
alone thermolysis of 2 in boiling toluene exclusively forms
single crystals of Ca(H2PO4)2·H2O, cothermolysis with
equimolar quantities of Ca(OMe)2 produced Ca(HPO4).
Significantly, the cothermolysis route can also be biased to
exclusively yield hydroxyapatite, an important CP phase in
treating many bone and dentistry related ailments. Although
the present work has made significant inroads into
a
Pathways a−c are further expanded in Scheme S1.
Scheme 3. Summary of Thermal Decomposition Studies of Polymer 2
H
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(CH3) and 78.34 ppm (CMe3). ESI-MS Calcd For C16H40CaO10P2
(Mr = 494.51):501.04 (M+Li)+ (calcd m/z 501.19).
decomposition landscape precursor 2, several further possibil-
ities exist in generating new materials, viz. CP-organic polymer
and CP-silica type hybrid materials. Our future work will
unravel these possibilities and further showcase the importance
of di-tert-butylphosphate-based metal complexes in materials
science.
Solid-State Thermolysis. Compound 1 (150 mg) was taken in
an alumina crucible and heated at 200, 400, 600, or 800 °C at an
heating rate of 10 °C/min for 8 h followed by slow cooling to result in
calcium metaphosphate materials 1-200, 1-400, 1-600, 1-700, and 1-
800 (β-Ca(PO3)2), respectively. Yield: 15−20 mg (65−85%). FT-IR
(as KBr pellets, cm−1): 3289(br), 1141(s), 911(s), 744(s), 545(s) for
1−200; 1236(s), 1126(s), 1089(s), 958(s), 568(s), 496 for 1−400;
1258(s), 1122(s), 1051(s), 939(s), 791(s), 550, 565 for 1−600;.
1275(s), 1131(s), 1087(s), 942(s), 710(s), 527 for 1-800.
Following a similar procedure, compound 2 (100 mg) was also
thermolyzed at 200, 400, 600, 700, or 800 °C at an heating rate of 10
°C/min for 8 h followed by slow cooling to result in calcium meta
phosphate materials 2-200, 2-400, 2-600 (α-Ca(PO3)2), 2-700, and 2-
800 (β-Ca(PO3)2), respectively. Yield: 25−30 mg (65−80%). 31P CP-
MAS NMR (202.47 MHz): δ −26.95, −28.58, −30.41, −33.67,
−35.56, −37.3 ppm for 2−600 (α-Ca(PO3)2; δ 30.39, −32.94,
−33.43, −34.97 ppm for 2−800 (β-Ca(PO3)2). FT-IR (as KBr pellets,
cm−1): 3404(br), 1115(s), 992(s), 913(s), 547(s) for 2−200;
1236(s), 1124(s), 1089(s), 958(s), 666(s), 496 for 2−400; 1259(s),
1128(s), 1082(s), 945(s), 792(s), 515(s) for 2−600; 1250(s),
1062(s), 960(s), 786(s), 567(s), 518 for 2−700; 1276(s), 1131(s),
1087(s), 942(s), 711(s), 528 for 2−800.
Solvothermal/Hydrothermal Decomposition. Synthesis of
Ca(H2PO4)2·H2O. Compound 1 (150 mg) in toluene (10 mL) (as
heterogeneous solvent) was taken in a Pyrex tube of dimensions 10 ×
8 mm (o. d. × i. d.). The tube was frozen at 77 K (liquid nitrogen
bath) by three freeze−pump−thaw cycles and flame-sealed under a
vacuum. The sealed tube was placed in an oven at 140 °C (heating
rate 10 °C/min) for 2 days to yield highly crystalline Ca(H2PO4)2·
H2O. The compound was isolated by filtration and the byproduct
H3PO4 washed with methanol. Yield: 21 mg (72%). FT-IR (as KBr
pellets, cm−1): 3170(br), 1127(s), 1063(s), 995(s), 892(s), 579(s),
562(s).
EXPERIMENTAL SECTION
■
Methods and Materials. Syntheses of 1 and 2 were carried out
under nitrogen using Schlenk techniques. Solvents were purified
according to standard procedures prior to their use. Commercially
available chemicals such as CaH2 (Spectrochem), Ca(OAc)2 (s.d.
Fine), Ca(OMe)2 (Sigma-Aldrich), and CaO (Spectrochem) were
purchased and used as received. Di-tert-butyl phosphate was
synthesized by following an earlier reported procedure.77 Infrared
spectra were obtained on a Perkin−Elmer Spectrum One FT-IR
spectrometer as KBr diluted discs. Elemental analyses were performed
on a Thermo Finnigan (FLASH EA 1112) microanalyzer. NMR
studies were performed on Bruker Avance DPX-400 and 500 MHz
spectrometers. Thermogravimetric analyses were carried out on a
Perkin−Elmer Pyris thermal analysis system under a stream of
nitrogen gas at the heating rate of 10 °C/min. The ESI MS studies
were carried out on a Bruker MaXis impact mass spectrometer.
Powder X-ray diffraction (including variable-temperature studies)
were recorded on a Rigaku (SmartLab SE) diffractometer using Cu
Kα radiation (λ = 1.54190 Å).
Bulk thermolysis studies were carried out under air in a muffle
furnace. The microstructure and morphology of CP ceramic materials
were investigated using high-resolution transmission electron micro-
scope (Tecnai G2, F30) equipped with a field-emission source
operating at 300 keV to image the nanocrystals on carbon coated
copper TEM grids. The samples were dispersed in isopropanol and
drop-casted on the TEM grids. The morphologies of decomposition
products were studied using FEG-SEM on a JEOL model JSM-7600F
field-emission gun-scanning electron microscope operating at an
accelerating voltage of 0.1 to 30 kV. The samples were prepared by
drop-casting the powdered samples onto the carbon substrate. The
samples were sputtered with platinum prior to imaging.
Compound 2 (100 mg) was thermolyzed in toluene solution as
described above for 1 to form Ca(H2PO4)2.H2O. Yield: 33 mg (67%).
31P CP-MAS NMR (202.47 MHz): δ −3.01, −7.61 ppm. FT-IR (as
KBr pellets, cm−1): 3254(br), 1127(s), 1067(s), 889(s), 579(s),
562(s).
Synthesis of [Ca(dtbp)2(dtbp-H)4] (1). To a dispersion of
Ca(OMe)2(0.5 mmol, 51 mg) in petroleum ether (20 mL) taken in a
Schlenk flask was added a solution of dtbp-H(3 mmol, 630 mg) in
petroleum ether (20 mL) with stirring for 48 h at room temperature.
After removal of solvent from resultant mixture under vacuum,
compound 1 were extracted from hot petroleum ether, leaving out a
small amount of 2 as solid. Analytically pure product was obtained as
colorless cubelike crystals of 1 from petroleum ether solution over a
period of 2 days. Yield: 441 mg (68%). Mp > 200 °C. Anal. Calcd For
C48H112CaO24P6 (Mr = 1299.27) Found (Calcd): C, 43.93 (44.37);
H, 8.71 (8.69). FT-IR (KBr pellet, cm−1): 3494(br), 2978(s),
2933(s), 1651(s), 1367(s), 1255(s), 1217(vs), 1087(vs), 1006(s),
Synthesis of Ca(HPO4) from 2. A solution of 2 (0.195 mmol, 100
mg) in methanol (5 mL) was added to a suspension of Ca(OMe)2
(0.195 mmol, 20 mg) in methanol solution (5 mL) taken in a
autoclave. The autoclave was placed in an oven at 150 °C (at a
heating rate of 10 °C/min) for 2 days followed by slow cooling to
yield crystalline Ca(HPO4), which was isolated by filtration and
washed with methanol. Yield: (24 mg, 45%). 31P CP-MAS NMR
(202.47 MHz): δ −4.61 ppm. FT-IR (as KBr pellets, cm−1):
3388(br), 1471(s), 1131(s), 1064(s), 874(s), 580(s).
Synthesis of Ca10(PO4)6(OH)2 from 2. CaO (0.455 mmol, 25.5 mg)
and 2 (0.195 mmol, 100 mg) were taken in a molar ratio of 7:3 in a
mortar and finely ground for 30 min. The resultant solid was digested
in distilled water (8 mL) and transferred to a hydrothermal vessel.
The autoclave was placed in an oven and heated to 140 °C at a
heating rate of 10 °C/min and held at this temperature for 2 days.
Cooling down the autoclave over 7−8 h yielded a white precipitate.
The precipitate was washed with methanol and dried under a vacuum
for 2 h to afford nanocrystalline HA. Yield: (46 mg, 70%). 31P CP-
MAS NMR (202.47 MHz): δ 3.43 ppm. FT-IR (as KBr pellets,
cm−1): 3434(br), 1098(s), 1032(s), 633(s), 602(s), 563(s).
Single-Crystal X-ray Diffraction Studies. X-ray diffraction data
were collected on a Rigaku Saturn 724+ CCD diffractometer fitted
with a microfocus Mo−Kα (λ = 0.7107 Å) radiation source. Data
collection, data integration and indexing were performed with the
CrysAlisPro software78 suite. All calculations were carried out using
the programs in the WinGX module79 and Olex 2.180 software by
direct methods (SIR-97).81 The final structure refinement was carried
out using full least-squares methods on F2 using SHELXL-2014.82 All
atoms were refined anisotropically. Crystal data and structure
refinement details for 1 and 2 are given in Table 1. Because the
1
971(vs), 825(s) cm−1. H NMR (CDCl3,400 MHz): δ 1.44 ppm (s,
36C). 31P NMR (CDCl3,162 MHz): δ −9.30 ppm. 13C NMR
(CDCl3,100 MHz): δ 30.03 (CH3) and 79.87 ppm (CMe3). ESI-MS
Calcd For C48H112CaO24P6 (Mr = 1299.27): 1337.61 (M+K)+ (calcd.
m/z 1337.52).
Synthesis of [Ca(μ-dtbp)2(H2O)2·H2O]n (2). A solution of dtbp-
H(2 mmol, 420 mg) in petroleum ether (20 mL) was added to a
dispersion of CaH2 (1 mmol, 42 mg) in petroleum ether (10 mL)
taken in a Schlenk flask. The resultant mixture was stirred for 24 h at
room temperature to yield 2 as a white precipitate that was separated
by filtration. Analytically pure product was obtained as colorless
fiberlike crystals of 2 from a methanol solution of the above
precipitate left undisturbed on a benchtop for over 4 days. Yield: 368
mg (72%), Mp > 200 °C. Anal. Calcd For C16H40CaO10P2 (Mr =
494.51) Found (Calcd): C, 38.61 (38.86); H, 8.03 (8.15). FT-IR (as
KBr pellets, cm−1): 3480(br), 2976(s), 2932(s), 1367(s), 1254(s),
1
1217(s), 1088(s), 1007(s), 975(s) cm−1. H NMR (CD3OD, 400
MHz): δ 1.43 ppm (s, 36H), 4.91 ppm (s, 4H). 31P NMR (CD3OD,
162 MHz): δ −8.33 ppm. 13C NMR (CD3OD, 100 MHz,): δ 30.64
I
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Notes
Table 1. Crystallographic Details of Compounds 1 and 2
The authors declare no competing financial interest.
1
2
identification code
empirical formula
FW
temp (K)
cryst syst
wavelength (Å)
space group
a (Å)
b (Å)
c (Å)
α (deg)
β (deg)
SV-16-7
SV-248
C16H42CaO11P2
512.51
ACKNOWLEDGMENTS
■
C48H112CaO24P6
1299.27
293(2)
triclinic
0.7107 (MoKα)
P-1
13.0633(5)
13.1898(6)
13.3720(8)
116.768(5)
105.923(4)
99.979(4)
1856.19(18)
1
1.162
0.278
2.422−25.0
33051
6529
1.061
0.0887
0.2286
This work was supported by an EMR grant of SERB, New
Delhi (EMR/2017/002767), and a J. C. Bose Fellowship grant
(SB/S2/JCB-85/2014). S.V. acknowledges the University
Grants Commission, New Delhi, for a research fellowship.
The authors thank SAIF, IIT Bombay, and RIFC funded
central facilities for access to various instruments used in this
work.
293(2)
monoclinic
0.7107 (MoKα)
P 21/n
5.7851(2)
17.9405(7)
26.3074(8)
90
90.499(3)
90
2730.28(16)
4
1.247
0.392
2.270−25.0
20477
4802
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
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sı
Synthesis, crystallographic details, additional figures, and
spectral characterization (PDF)
Accession Codes
CCDC 2005743−2005744 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
■
Ramaswamy Murugavel − Department of Chemistry, Indian
Institute of Technology Bombay, Powai, Mumbai 400076,
India; orcid.org/0000-0002-1816-3225; Email: rmv@
chem.iitb.ac.in
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Sonam Verma − Department of Chemistry, Indian Institute of
Technology Bombay, Powai, Mumbai 400076, India;
orcid.org/0000-0003-1497-3420
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