Tenacic Acids: A New Class of Tenacious Binders to Metal Oxide Surfaces

Article abstract of DOI:10.1002/chem.201803242

The backbone of 2-hydroxyisophthalic acid was identified as a potential metal oxide anchor because of the perfect alignment of all three of its donor groups for binding to inorganic surfaces. It can therefore be used in the design of organic linkers for m

Full text of DOI:10.1002/chem.201803242

A Journal of
Accepted Article
Title: Tenacic Acids: a New Class of Tenacious Binders to Metal Oxide
Surfaces
Authors: Rajesh Komati, Carl Mitchell, Anastasia LeBeaud, Huy Do,
Galina Z Goloverda, and Vladimir L Kolesnichenko
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10.1002/chem.201803242
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Tenacic Acids: a New Class of Tenacious Binders to Metal Oxide
Surfaces
Rajesh Komati,[b] Carl A. Mitchell,[b] Anastasia LeBeaud,[b] Huy Do,[b] Galina Z. Goloverda*[a] and
Vladimir L. Kolesnichenko*[a]
Abstract: The backbone of 2-hydroxyisophthalic acid was identified
as a potential metal oxide anchor because of the perfect alignment
of all three of its donor groups for binding to inorganic surfaces. It
can therefore be used in the design of organic linkers for metal
oxide-based hybrid materials. Optimized and scalable methods for
the synthesis of 2-hydroxyisophthalic acid (1) and its 5-substituted
derivatives: 5-bromo- (2), 5-sulfooxy- (3), 5-hydroxy- (4), and 5-
designing such a head, an aqueous metal ion complexation
equilibrium would be an advantageous, yet simple, model
system to examine. Stronger ligands might seem to be the
obvious choice for this purpose.
For example, anionic
chelators/complexones such as alpha-hydroxycarboxylic acids
(citric, tartaric, etc.),[11] derivatives of catechol,[12-16] and
phosphonic acids,[17-19] have been found to be effective colloid
stabilizing agents. On the other hand, the complexones often
bind so strongly to a SINGLE metal center that they leach metal
ions from the surface, leading to nanoparticle degradation,[18,20]
PEG600 (5) are presented.
Dynamic Light Scattering (DLS)
demonstrated that (2) inhibits Fe(OH)3 precipitation when FeIII
aqueous solutions are titrated with NaOH, while similar titrations in
the presence of the structurally-related isophthalic and salicylic acids, and in the extreme, to its complete dissolution if enough
both missing the third donor group, show turbidity at pHs as low as
2.3 and 3.5, respectively. The adduct synthesized from 4.5 nm
γ-Fe2O3 nanoparticles and (5) is water-, alcohol- and CH2Cl2-soluble,
and forms stable aqueous colloids in the pH range of 4.4-8.7.
Moreover, at a pH close to neutral these colloids survive at 100ºC,
demonstrating the high practicality of 2-hydroxyisophthalic acid for
nanoparticulate inorganic/organic hybrid material design.
complexone is present. The molecular geometry of an ideal
linker’s coordinating backbone would have its donor atoms
positioned for a MULTIPLE-SITE attachment to metal oxide
surface in a bridging binding mode.
Even though our earlier experience with phthalic and
isophthalic acids showed that they were relatively weak ligands
for iron oxide nanoparticles as compared to citric and tartaric
acids,[11] the aromatic acids were still more appealing due to
their higher propensity for derivatization. We proposed to
strengthen the aromatic linker head’s binding capacity by adding
a phenolic OH-group between the two carboxylates in the
isophthalate metal oxide-coordinating core. The idea was that
the resulting tridentate ligand would preferentially bind in a
bridging mode to at least two neighboring metal ions (η3:μ-
bridging), as shown in Scheme 1a. The ligand presented in this
scheme is 2-hydroxyisophthalic acid, and to the best of our
knowledge, there are no reports in the literature on its surface
and colloidal chemistry.
Introduction
Many areas of modern technology rely on composite materials
with a broad spectrum of chemical and physical properties. For
example, nanoparticulate imaging and delivery agents for
theranostic applications often contain a superparamagnetic iron
oxide core and an organic shell with a targeting peptide,
fluorescent dye, or drug molecule attached.[1-6] Similarly,
materials for photovoltaics are commonly made up of a
semiconductor with an attached dye or quantum dot sensitizer.[7-
10]
Normally, a linker whose structure and composition are
optimized for binding, connects the two components in these
materials. Metal oxides, for instance, can be connected to
organic parts of the material by including oxygen-donor ligands
in the linker. A primary goal of this work was to develop new
linkers with an easily functionalizable structure and
a
coordinating head with optimal binding capacity for metal oxide
surfaces.
Scheme 1. (a) A hypothetical binding mode of 2-hydroxyisophthalic acid to the
solid iron oxide surface; (b) quinol tetracarboxylic acid.
For a biomedical application, it is important that the
nanoparticulate adduct be hydrolytically stable, which can be
secured by the nature of the linker’s coordinating head. When
Our target molecule may be also viewed as a derivative of
salicylic acid, which is known to form moderately strong
complexes with metal ions in aqueous solutions.[21] Considering
the binding mode displayed in Scheme 1a, it appeared
reasonable to expect that an extra carboxyl group added to the
salicylic acid molecule would not contribute to the strength of a
single metal ion complexation. However, the resulting molecule
might be an effective bridging ligand for binding to an inorganic
surface with minimal risk of leaching metal ions out. Since no
derivatives of 2-hydroxyisophthalic acid are commercially
available, one of the aims of this work was its synthesis and
functionalization.
[a]
Drs. G.Z. Goloverda and V.L. Kolesnichenko
Chemistry Department
Xavier University
New Orleans, Louisiana 70125, USA
E-mail: gzgolove@xula.edu; vkolesni@xula.edu
Dr. R. Komati, C.A. Mitchell, A. LeBeaud, H. Do
Chemistry Department
[b]
Xavier University
New Orleans, Louisiana 70125, USA
Supporting information for this article is given via a link at the end of
the document.
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The first report of derivatives of 2-hydroxyisophthalic acid
was made by John U. Nef (1862-1915) as early as in 1888.[22]
Focusing on the synthesis of the carboxylate derivatives of p-
benzoquinone, Nef performed a multiple-step synthesis to obtain
Synthesis of 5-bromo-2-hydroxyisophthalic acid (2) was
completed by Duff formylation[48,49] of 5-bromosalicylic acid
followed by oxidation with sodium chlorite. Synthesis of 2-
hydroxy-5-(sulfooxy)isophthalic acid potassium salt (3) was
accomplished by Elbs persulfate oxidation[50] of (1). This
compound was used as a precursor for the formation of 2,5-
dihydroxyisophthalic acid (4), synthesized through its bromide-
assisted acidic hydrolysis. Synthesis of the 2-hydroxyisophthalic
acid conjugate with polyethylene glycol (PEG-600) (5) was
accomplished in two steps, starting with intermediate (4). In the
first step, PEG-600 was tosylated with tosyl chloride in the
presence of triethylamine. In order to minimize the formation of
the ditosylated derivative, the synthesis was performed with a
large excess of PEG and in a dilute dichloromethane or
chloroform solution. In the second step, nucleophilic substitution
of the tosylated PEG-600 with (4) in basic aqueous solution
yielded the target conjugate, which was freed from the sodium
tosylate by-product and excess PEG by elution through a base-
activated DOWEX-1 resin column.
quinol tetracarboxylic acid.
The structure of quinol
tertacarboxylic acid, with its two identical sets of functional
groups facing in opposite directions (Scheme 1b), might be
advantageous for supramolecular chemistry and photovoltaics.
However, hybrid materials for biomedical applications would
benefit more from a family of “single-faced” ligands that can be
chemically modified at the site of substituent X (Scheme 1a).
There are only four synthetic procedures found in the
literature for the preparation of unsubstituted,[23-27] 4,6-
disubstituted[28-30] and 5-substituted[31-33] derivatives of 2-
hydroxyisophthalic acid. To the extent of our knowledge, the
only attempt to directly functionalize 2-hydroxyisophthalic acid
suffered from low yield and ill characterization.[24] There were
several reports on the coordination chemistry of 2-
hydroxyisophthalic acid with copper(II), where this ligand was
generated in situ by oxidation of isophthalic acid with Cu(II).[34-39]
Relatively scarce studies of 2-hydroxyisophthalic acid and
its derivatives include solution phase beryllium complexation,[27]
structural
coordination
chemistry,[34-41]
luminescence
properties,[41] supramolecular chemistry,[26,42,43] crystal structure
and acid/base properties,[44] and hydrolysis kinetics.[45,46]
Herein we report the synthesis of an unsubstituted acid (1)
and of its 5-substituted derivatives with X = Br (2), OSO3- (3), OH
(4) and PEG600 (5) substituents. Also, we demonstrate a high
affinity of 2-hydroxyisophthalate backbone to metal oxide
surfaces, and the ability of its derivatives to stabilize iron oxide
aqueous colloids via electrostatic and steric mechanisms.
Scheme 2. Synthesis of 2-hydroxyisophthalic acid and its 5-substituted
derivatives.
Results and Discussion
Interaction with metal oxide surfaces. The affinity of 2-
hydroxyisophthalic acid to inorganic oxide surfaces was first
Ligands synthesis and properties Synthesis of the parent 2-
hydroxyisophthalic acid (1) was accomplished by PbO2 oxidation
of 3-methylsalicylic acid in KOH melt[23-25] (Scheme 2). Our
modification of this method helped to reduce the amount of time
needed for the reaction and to eliminate the fire and inhalation
hazards without any loss in yield or quality of the product. This
relatively stable substance can be easily purified by
recrystallization from hot water (from which it crystallizes as a
monohydrate) or by vacuum sublimation at 200oC. Its room-
temperature (22°C) solubility in water was found to be 2.6 g/L.
The substance is a triprotic acid with pKa’s 1.92, 4.57 and 11.1
(details will be reported elsewhere). The monohydrate loses its
crystallization water above 100oC and the anhydrous compound
melts with decomposition at 253-255oC. The substance resists
oxidation by oxygen or lead(IV) oxide, but its benzene ring
undergoes electrophilic aromatic substitution via nitration, azo-
coupling[47] and Elbs persulfate oxidation (details are given
below) reactions, which opens up a variety of pathways for its
derivatization.
evidenced by thin-layer chromatography (TLC).
2-
hydroxyisophthalic acid, 5-hydroxyisophthalic acid, and salicylic
acid were compared side-by-side on normal phase TLC plates
impregnated with UV254 fluorescent indicator. Using an eluent of
8:2 (v/v) ethyl acetate/acetic acid the Rf values were 0.41, 0.75
and 0.78, respectively, indicating a significantly stronger binding
of the named (1) acid to silica, which is a relatively acidic oxide.
The affinity of 2-hydroxyisophthalate moiety to iron oxide
surfaces was then evaluated by testing its ability to inhibit the
precipitation of iron(III) hydroxide from aqueous solutions of FeIII
against the same ability of the structurally related isophthalic and
salicylic acids (which have only two coordinating groups on the
ring). Three aqueous solutions containing iron(III) and one of
the above acids were prepared and titrated with a NaOH
solution while monitoring by Dynamic Light Scattering (DLS).
Solution (a) contained 5-bromo-2-hydroxyisophthalic acid (2)
(Fe:L = 2:3); solutions (b) and (c) contained salicylic and 5-
hydroxyisophthalic acids (Fe:L = 1:3), respectively. The acid (2)
was superior to the reference salicylic and 5-hydroxyisophthalic
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acids, as it was the only one able to inhibit precipitation of iron
hydroxide under neutral and basic conditions (Fig.1).
this agent can also facilitate solubility of the nanoparticulate
adduct in different solvents. For example a spacer composed of
hydrocarbon chains can make the inorganic/organic adduct
lipophilic while a polyether-like spacer can make it amphiphilic.
In this study we have chosen PEG600 as a suitable spacer and
conjugated it with 2-hydroxyisophthalate moiety to produce (5).
This choice was justified for very small iron oxide nanoparticles
used in this study. [15,51,52]
The 4.5 nm maghemite (γ-Fe2O3) nanoparticles were
synthesized in
a form of a surfactant-free non-aqueous
(diethylene glycol) colloid. This was accomplished by high-
temperature hydrolysis of chelated iron(II,III) alkoxide complexes,
followed by room-temperature oxygenation. Minor modification
of our earlier reported method[11,53] simplified the procedure and
permitted more accurate control over the total concentration of
iron in the resulting colloids. As we have shown,[11,53] the
reaction conditions used for these syntheses are sufficient for
converting all iron precursors into non-aggregated nanoparticles
in quantitative yield (TEM image and XRD are shown in Fig.
Figure 1. Light scattering as a function of pH in the DLS-monitored titration of
iron(III) aqueous solutions containing 5-bromo-2-hydroxyisophthalate (solution
a, green curve), salicylate (solution b, red curve), and isophthalate (solution c,
blue curve). Note: higher light scattering intensity is due to a greater
aggregation. The former effectively inhibits precipitation of hydrated iron(III)
oxide in the reference reaction Fe3+ + 3OH- → Fe(OH)3.
S25).
Diethylene glycol colloids of the obtained 4.5 nm
nanoparticles were reacted with (1) or (5) producing the surface-
coated nanoparticulate adducts. The added amount of ligand
was based on the known nanoparticles’ concentration and size.
The reaction stoichiometry was calculated so that each ligand
molecule bound to two metal atoms on the nanoparticle’s
surface[11] (see p. S27 in SI file for details).
Based on visual evidence - ligand-free (except for H2O and
Cl-) FeIII solutions turn from yellow to deep red-purple upon
addition of (1) or (2) – and UV-Vis data (Fig.S24), it can be
concluded that the solution (a) at low pH contained iron in a form
of coordination complex. This observation is in line with the
known property of iron(III) to complex salicylic acid,[21] but not
isophthalic acid, which did not cause any notable color change.
As the pH was raised during titration, the characteristic colors in
(a) and (b) rapidly faded, resulting in a clear orange solution with
(a) and turbid orange one with (b); the originally clear yellow
isophthalate-containing solution (c) rapidly turned turbid orange
at a pH as low as 2.5. The DLS and UV-Vis data (Fig.S24)
evidenced that the most likely form of iron in (a) above pH 5 was
colloidal iron(III) hydroxide. It is our hypothesis that the original
(pH 2) iron 2-hydroxyisophthalate complex in this solution is not
particularly strong and the equilibrium shifts significantly towards
its dissociation as the pH is raised. Thus, the complex
undergoes partial dissociation, hydroxylation, and condensation,
resulting in the formation of very small iron (hydr)oxide
nanoparticles with (2) coating the surface – likely with the same
binding mode as in the original complex (Scheme 1a). This also
The DLS-monitored pH titrations were performed on
aqueous Fe2O3 colloids (1.0 g of stock diethylene glycol colloid
per 10 mL total volume) with the initial FeIII concentration of
0.005M (Fig 2). A ligand-free Fe2O3 colloid (control) could be
kept peptized only at pH values of 5.5 and lower (red curve in
Fig.2). Colloids containing particles coated with the parent acid
(1) showed the opposite behavior: at low pH the colloids
aggregated; stable aqueous colloids formed in the pH range of
5.2 to 8.2 (blue curve in Fig. 2). This observation was in line
with the expected electrostatic colloid stabilization mechanism,
which is pH-dependent.
correlates
with
2-hydroxyisophthalate
complexation
stoichiometry with Be and complex stability trends for Be, Al, Cr,
Fe, Cu, Zn, Cd and Pb ions.[27]
Figure 2. Light scattering as a function of pH in Fe2O3 (4.5 nm) aqueous
colloids: the original ligand-free colloid (red), a colloid with nanoparticles
coated with 2-hydroxyisophthalic acid (blue), and a colloid containing particles
coated with 2-hydroxyisophthalic acid-PEG600 conjugate (green). Note:
higher light scattering intensity is due to a greater aggregation.
2-hydroxyisophthalate-coated Fe2O3 nanoparticles Inorganic
nanoparticles, coated with common small-molecule ligands,
usually form aqueous colloids stabilized by an electrostatic
mechanism (electrical double-layers). It is likely that this
scenario is in place in a solution (a), Figure 1, at higher pHs.
Generally, the stability of such colloids is affected by the pH and
ionic strength of the medium. The same complexing agent, but
chemically modified with a spacer attached to its backbone, can
stabilize the nanoparticles’ colloid through a steric mechanism,
which is pH-insensitive. Depending on the nature of the spacer,
In order to obtain pH-insensitive colloids, we used (5) as
an amphiphilic steric stabilizing agent. Nanoparticulate adduct
of 4.5 nm Fe2O3 with (5), isolated in solid form, was found to be
water-, methanol-, ethanol- and dichloromethane-soluble.
According to DLS, it has formed stable aqueous colloids in the
studied range of pHs from 4.4 to 8.7 (green curve in Fig. 2) and
contained particles with a hydrodynamic diameter of 12 nm.
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NaOH and HCl. The elemental analyses were performed by Galbraith,
Inc. Powder X-ray diffractogram was obtained using Rigaku MiniFlex II
diffractometer. TEM images were obtained on JEOL JEM 2010
transmission electron microscope. FT-IR spectra were obtained on
Thermo Nicolet 380 spectrometer.
Moreover, these colloids remained unchanged at neutral pH
even after heating to 100ºC.
Further evidence of binding of the 2-hydroxyisophthalate
moiety to Fe2O3 nanoparticles was obtained from FT-IR spectra
of both adducts: with (1) and (5) (isolated in pure form) and from
the combustion analysis for the adduct with (1). The IR spectra
showed expected vibrational bands of the coordinated aromatic
carboxylate ligand (Fig. S26); spectrum of the adduct with (5)
showed additional vibrational bands corresponding to oligo-
ethylene oxide side substituent. Combustion analysis for Fe2O3
adduct with (1) detected that the content of Fe2O3 was 79.8%.
Calculation (see p. S27 in SI file for details), based on
assumption that 2-hydroxyisophthalate ligand is doubly-
deprotonated and bound to two surface iron atoms on the 4.5
nm nanoparticle, gave the Fe2O3 content of 80.28%.
2-hydroxyisophthalic acid (1). A 250-mL stainless steel beaker was
charged with 120 g of the granular KOH.H2O and 25 mL of water. After
cooling for 5 minutes, 20.0 g of 3-methyl salicylic acid were added to the
solution gradually while stirring with nickel spatula, followed by 120 g of
PbO2. The resulting mixture was flame-heated while intensive stirring
with a Bunsen burner. During 10-15 minutes heating session, the
mixture turned thicker first, and then softened, then liquefied, briefly
boiled, and changed its color from black to red. Heating was continued
until the melt became free-flowing and Pb3O4 formed as red crystals. The
reaction mixture was allowed to cool; the solidifying melt was loosened
by stirring. After cooling, the solid was treated with 300 mL of deionized
water and stirred until KOH melt dissolved and Pb3O4 separated from the
solution.
The crystalline red Pb3O4 fraction was separated by
decantation, and the yellow-orange microcrystalline fraction was
separated by a brief centrifuging. The precipitates were washed with
additional 2×50 mL of water, and all aqueous solutions were combined.
The resulting solution was acidified with the solution of sulfuric acid: 51
mL of a concentrated H2SO4 in 100 mL of water. Addition of sulfuric acid
was continued until the pH dropped to 7-8; the precipitation of PbSO4 at
this point was complete. The precipitated lead sulfate was separated by
centrifuging, and rinsed with water to improve the yield of the product.
The separated supernatant solution was further acidified with the
remaining sulfuric acid; this caused precipitation of the target product (1).
After cooling in an ice bath, the solid was filtered off on a medium glass
frit, washed with 0.1M HCl until a drop test with BaCl2 solution was
negative, then with icy water, and finally transferred in a dish and air-
dried. Yield of an off-white powder was 20.4 g (85%). No further
purification was needed for most purposes, however if desired, the
substance can be recrystallized from hot water. All lead-containing by-
products were washed with water, dried and recycled. Anal. Calc’d for
Conclusions
In conclusion, our hypothesis that 2-hydroxyisophthalic acid has
its two carboxyl groups and phenolic -OH ideally aligned for
strong binding to inorganic surfaces was supported. This moiety
would be a good precursor for an adjustable linker’s synthesis.
Because this acid and its derivatives are not commercially
available, the parent acid and its 5-substituted derivatives with X
-
= Br, OSO3 , OH and a conjugate with PEG600 have been
synthesized. The 2-hydroxyisophthalic acid derivatives inhibit
precipitation of iron(III) hydroxide from neutral and alkaline
aqueous solutions. The 5-(PEG600) derivative makes 4.5 nm γ-
Fe2O3 nanoparticles not only water-, ethanol- and
dichloromethane-soluble, but also capable of forming heat-
resistant aqueous colloids at neutral pH, and stable colloids at
room temperature in the studied pH range of 4.4-8.7.
.
C8H6O5 H2O: C, 48.00; H, 4.04. Found: C, 48.35; H, 4.02. HRMS (ESI)
calc’d. for C8H6O5 [M - H] 181.0142, found 181.0139. 1H NMR (400 MHz,
DMSO-d6) δ 7.93 (d, J = 7.6 Hz, 2H), 6.85 (t, J = 7.6 Hz, 1H).
The described findings, great potential for simple
derivatization and high stability open up a variety of applications
for 2-hydroxyisophthalic acid as a precursor in the synthesis of
linkers for organic/inorganic composite materials for biomedical
and solar energy uses. We define this acid and its derivatives
as being tenacious to metal oxide surfaces and propose to name
them “tenacic acids”.
5-bromo-2-hydroxyisophthalic acid (2)
The solution of 5-
bromosalicylic acid (1.74 g, 8 mmol) and hexamethylenetetramine (4.48
g, 32 mmol) in 20 mL of trifloroacetic acid was stirred at 90˚C for 12 h.
After completion and cooling to room temperature, 100 mL of 1 M HCl
were added and the reaction mixture was stirred for 6 h. The organic
product was extracted with ethyl acetate (3×100 mL). Combined organic
layers were washed with water and dried over sodium sulfate. Ethyl
acetate was removed under reduced pressure to get the 1.49 g of 5-
bromo-3-formylsalicyclic acid (a) with a 76 % yield.
Experimental Section
To a solution of (a) (0.74 g, 3 mmol) in 6 mL of DMSO, sodium
dihydrogenphosphate (0.094 g, 0.783 mmol) solution in 2 mL of water
was added. To this stirring solution, sodium chlorite (0.577 g, 6.38 mmol)
in 20 mL of water was added dropwise and the reaction mixture was
stirred at room temperature about 3 h. After completion, the pH was
lowered to 2 by addition of sulfuric acid and the solution was cooled to
~10°C. After 3 hours, the precipitate was filtered off and dried under
vacuum to get 0.519 g of the pure product with 62% yield.
General
All reagents and solvents were of the reagent grade
purchased from ACROS or Aldrich. NMR spectra were recorded on
Agilent 400MR spectrometer. Routine electrospray mass-spectra were
obtained on a Thermo Finnigan TSQ Ultra instrument. High-resolution
mass spectra were obtained on Thermo Q-Exactive LC/MS/MS System
and on Agilent Technologies 6530 Accurate Mass QTofLC/MS (at the
University of Texas at Austin mass-spectrometry facility). Dynamic light
scattering (DLS) experiments were performed with a Malvern Zetasizer
Nano ZS instrument combined with a MPT-2 automatic titrator. The initial
concentrations were: FeIII - 1.5 mmol/L, (2) – 2.25 mmol/L, salicylic and
5-hydroxyisophthalic acids – 4.5 mmol/L, NaOH (titrant) – 0.25M. In the
experiments with Fe2O3 nanoparticles and (1) and (5), the initial [FeIII]
was 5×10-3M, [L] was 5.5×10-4M, and titrations were done with 0.01M
Anal. Calc’d for C8H5O5Br.H2O: C, 34.43; H, 2.53. Found: C, 34.92; H,
2.43. HRMS (ESI) calc’d. for C8H5O5Br [M - H] 258.9248, found 258.9240.
1H NMR (400 MHz, DMSO-d6) δ 7.95 (s).
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2-hydroxy-5-(sulfooxy)isophthalic acid, K salt (3) (a) Ten mmol (2.00
g) of the recrystallized (1) was suspended in 20 mL of water; 17.0 mL of
5.0M aqueous NaOH was added, resulting in a complete dissolution of
the acid. The solution was chilled on ice. A solution of 10 mmol of
Na2S2O8 (2.38 g) in 10 mL of water was added dropwise under stirring.
Rate of the addition was adjusted so that the temperature did not exceed
10°C. The reaction solution was sealed and left at room temperature for
~8 hours.
solution was evaporated in vacuum at 60°C to dryness; the oily residue
was dissolved in chloroform, the leftovers of tosic acid were extracted
with water, and the organic layer was dried with drierite and evaporated
yielding 50 mg of the product (not optimized). 1H NMR (400 MHz, CDCl3)
δ 7.83 (s, 2H); 3.65 (s, 80H). ESI-MS [M-H], found: cluster of peaks
505.40-1077.44 spaced by m/z 44.0 (CH2CH2O), with maximum at m/z
769.3490.
Calcd
for
C8H5O6(CH2CH2O)13
H
(-H):
769.3489.
Fragmentation of every ion from this cluster gave the same pattern
typical for all 2,5-dihydroxyisophthalic acid derivatives: m/z = 108, 152
and 196.
(b) The ice-chilled reaction solution was acidified with 1M HCl to pH ~1.
Unreacted 2-hydroxyisophthalic acid (1) was quickly extracted with four
portions of 25 mL of MTBE/CH2Cl2 (2:1) mixture (the organic solution
was rotary-evaporated and the unreacted (1) (0.6 g) was recovered and
reused in the next sulfatation procedure. A solution of potassium
bisulfate (20 mmol, 2.7 g) in 10 mL of water was added to the reaction
solution with agitation, and the solution was left at ~10°C overnight. A
crystalline product was isolated by filtration and washing with
concentrated KHSO4 solution before it was used for synthesis of (4). For
the analytical purposes, a pure substance was obtained by washing with
10 mL of chilled 0.1M HCl, then with MTBE and dried under open air at
ambient temperature and then at 105°C. The yield of the off-white
powder was 1.50 g (70%). For analysis, the sample was dried at 110°C
overnight followed by combustion at 800°C; the residue was identified as
K2SO4. Calcd: 27.5%. Found: 26.9%. 1H NMR (400 MHz, DMSO-d6) δ
7.71 (s). ESI-MS calc’d. for C8H6SO9 [M-H] 277, found 277; [½M-H] 138,
found 138. Fragmentation of these peaks followed the expected path in
MS-MS runs.
Diethylene glycol γ-Fe2O3 colloid. All reagents were used in the form
of stock solutions in diethylene glycol: FeCl3 and FeCl2 - 0.5 mol/kg each;
H2O - 1 mol/kg; and NaHdeg - 1.3 mol/kg (obtained by reacting Na metal
with diethylene glycol). All manipulations (except for oxygenation) were
done in the nitrogen atmosphere of a glovebox. In a typical procedure,
solutions of FeCl3, FeCl2, H2O and NaHdeg were mixed in the following
proportion*: 6 g (3 mmols) + 3 g (1.5 mmols) + 7 g (7 mmols) + 10 g (13
mmols). The obtained green-brown solution was mixed with 64 g of
diethylene glycol and the temperature was raised from 25 to 180°C in 20
min. Heating at this temperature was continued for ~2 hours, and then at
220°C for ~1 hour. The resulting colloid was completely homogeneous,
so no purification was necessary. Overall iron concentration in the
obtained this way Fe3O4 colloids was [Fe] = 0.050 mol/kg.
*Note: special care should be taken when these solutions are transferred
and mixed, as their high viscosity can cause serious deviations from the
desired reaction stoichiometry, what in turn, can alter the properties of
the resulting colloid.
2,5-dihydroxyisophthalic acid (4) A suspension of (3) (1.10 g, 3.48
mmol) in 20 mL of water was mixed with 6 mL 25% HCl and 0.2 g of
NaBr. The reaction mixture was brought to 80°C and stirred for about 2
hours. As reaction progressed, the solution turned clear and by the end
of the reaction, a white crystalline precipitate formed. The reaction
mixture was cooled down to a room temperature and a white precipitate
was filtered, washed with 0.1 M chilled HCl and dried to produce 2,5-
dihydroxyisophthalic acid (4) (0.65 g) as a white powder with an isolated
Colloids of γ-iron(III) oxide (maghemite) were obtained by room
temperature oxygenation of the magnetite colloids with dry O2 for 1 week.
Vigorous stirring helped to speed up the process. During oxygenation,
the color of the solutions changed from brown-black to deep orange-
brown.
.
yield of 86%. Anal. Calc’d for C8H6O6 H2O: C, 44.45; H, 3.74. Found: C,
γ-Fe2O3 nanoparticulate adduct with (1). A 10 mL aliquote of 0.010M
aqueous monobasic sodium 2-hydroxyisophthalate was added to 20 g of
diethylene glycol γ-Fe2O3 colloid (0.050 mol/kg) under intensive stirring.
After 1 hour at room temperature, the resulting homogeneous solution
was heated at 100°C for 1 hour, cooled and mixed with 10 mL of water.
No visible change was noted: the colloid was transparent deep red. This
colloid was acidified with 0.1M hydrochloric acid to pH ~3. This caused
coagulation. The solid was separated from solution using magnet,
washed with water (3×50 mL) and dried under open air at ~40°C and
finally at 105°C for 1 hour. The isolated yield of dark brown solid was 78
mg. The samples for combustion analysis were dried at 150°C until
constant weight.
44.55; H, 3.49. 1H NMR (400 MHz, DMSO-d6) δ 7.36 (s). ESI-MS calc’d.
for C8H6O6 [M-H] 197.0092, found 197.0086.
2-hydroxy-5-(PEG600)isophthalic acid (5) (a) PEG600 tosylation. A
solution of 6.0 g (10 mmol) of PEG600 in 10 mL of dichloromethane was
mixed with 0.382 g (2 mmol) of tosyl chloride dissolved in 2 mL of
dichloromethane. A 1.4 mL portion of trimethylamine (10 mmol) was
added to the resulting solution dropwise while stirring. After 12 hours of
aging at ambient conditions, the resulting colorless solution was rotary
evaporated, and the residue was redissolved in 10 mL of toluene. The
byproduct triethylammonium chloride, crystallized out as colorless
needles, was filtered off, washed with toluene, and the combined toluene
solution was rotary-evaporated and then dried at 60°C and 80 mbar
pressure yielding 6.24 g of oily colorless product.
γ-Fe2O3 nanoparticulate adduct with (5). A 0.5 mL aliquote of 0.011M
methanol solution of 5-(PEG600)-2-hydroxyisophthalic acid was added to
1.0 g of diethylene glycol γ-Fe2O3 colloid (0.050 mol/kg) under intensive
stirring. After 1 hour at room temperature, the resulting homogeneous
solution was heated at 100°C for 1 hour, cooled, mixed with 1 mL of
water, heated again for 1 hour at 100°C and finally at 60°C overnight. No
visible change was noted: the colloid was transparent deep red. The
solvent was evaporated under high vacuum at 50°C yielding dark red-
brown solid. This solid was dissolved in ethanol and dichloromethane
(1:1), the solution was centrifuged and decanted to remove the by-
product NaCl and evaporated. Solid residue was washed with MTBE and
dried to yield 9.6 mg of the product.
(b) A 55 mg (0.25 mmol) portion of (4) was dissolved in 5.0 mL of 0.10M
aqueous NaOH under nitrogen blanket and pH of the solution was
adjusted to 10. Tosylated PEG600 (1.0 g of 20% reagent) was added
with intensive stirring. The reaction solution was heated overnight at
96°C under nitrogen protection. After cooling, new 1
g portion of
tosylated PEG600 was added and heating was resumed for another 12
hours. After cooling, the solution was diluted with equal volume of water
and acidified with 0.1M HCl to pH 1. The reaction solution was treated
with base-activated DOWEX-1 resin on the column, which caused
adsorption of the product, unreacted dihydroxyisophthalic acid and tosic
acid. The unreacted PEG600 was removed by flushing the column with
water, followed by 0.1M HCl to isolate the product. The resulting aqueous
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10.1002/chem.201803242
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FULL PAPER
Synergistic effect of the three donor
groups in 2-hydroxyisophthalic acid
secures its strong covalent binding to
metal oxide surfaces. Herein we have
demonstrated its ability to form stable
adducts with iron oxide at a wide
range of pHs, drastically improving
their practicality in functional hybrid
materials’ design.
Rajesh Komati, Carl A. Mitchell,
Anastasia LaBeaud, Huy Do, Galina Z.
Goloverda* and Vladimir L.
Kolesnichenko*
Page No. – Page No.
Tenacic Acids: a New Class of
Tenacious Binders to Metal Oxide
Surfaces
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