A simple chemical model for clathrate hydrate inhibition by polyvinylcaprolactam

Article abstract of DOI:10.1039/c1cc13556b

A dimeric model compound gives structural insight into the mode of interaction of low dosage hydrate inhibitors with water.

Full text of DOI:10.1039/c1cc13556b

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COMMUNICATION
A simple chemical model for clathrate hydrate inhibition by
polyvinylcaprolactamw
John R. Davenport,a Osama M. Musa,*b Martin J. Paterson,c Marc-Oliver M. Piepenbrock,a
Katharina Fuckea and Jonathan W. Steed*a
Received 15th June 2011, Accepted 15th July 2011
DOI: 10.1039/c1cc13556b
A dimeric model compound gives structural insight into the mode
of interaction of low dosage hydrate inhibitors with water.
crystalline methane structure I hydrate resulted in hydrate
melting.16 A two-step mechanism of KHI action has been
proposed involving (a) disruption of local water order in liquid
water by KHIs and (b) inhibitor binding to the growing crystal
surface.15,16 Other work conflicts with step ‘b’ and suggests
that PVP increases interfacial surface energy without surface
binding.17 A further hypothesis emphasises kinetic factors.16
We now report the synthesis of a small molecule model for
PVCap containing two monomer repeat units, and present
experimental, structural and DFT studies on its interaction
with water. We show that this simple compound represents an
appropriate model for commercial KHIs.
Gas clathrate hydrates present a very real challenge to the
petrochemical industry, because in uninhibited systems they
can agglomerate to form plugs within transport pipelines with
consequent severe financial and safety implications.1 This
problem is increasingly successfully obviated using kinetic
hydrate inhibitors (KHIs) which inhibit clathrate hydrate
formation at concentrations as low as 0.5 wt%, significantly
reducing the inhibition costs.2 Generally the most successful
kinetic hydrate inhibitors are polymers that contain small
cyclic amides, particularly based on 5-membered (pyrrolidone)
or 7-membered (caprolactam) rings (Scheme 1), either in the
form of polyvinylcaprolactam (PVCap) and polyvinylpyrroli-
dinone (PVP) or copolymers such as poly(VP/VCap), VC-713
and VIMA (N-methyl-N-vinylacetamide-vinylcaprolactam).2–4
The global market for KHIs is substantial and includes major
brands such as International Specialty Products (ISP) ‘Inhibex’
range of co-polymers based on vinyl caprolactam. Novel
acryloyl pyrrolidine and isopropylacrylamide (IP) polymers
have also recently been reported.5 While there have been
extensive studies on clathrate hydrate nucleation6 and the
mechanism of inhibition of hydrate formation by KHIs7–13
including molecular dynamics studies based on VCap monomer14,15
the process is not yet well understood. Vinyl caprolactam
monomer, simulations suggest that the 7-membered ring
backbone is included within the open face of a partially
formed hexakaidecahedral cavity in the growing hydrate
crystal.15 Monomer-based studies, however, cannot directly
address the effect of polymer steric requirements and coopera-
tivity between adjacent lactam units. A recent MD simulation
involving an 8-monomer PVP oligomer suggests significant
interaction between the polar amide oxygen atoms and bulk
water, although simulations of polymer in the presence of
Reaction of VCap with trifluoroacetic acid under conditions
reported18 to dimerise the analogous VP results in the clean
isolation of unsaturated dimer 1 in quantitative yield. Reduction
to the saturated 2 can be achieved quantitatively using a
ThalesNano H-Cubes Continuous-flow hydrogenation reactor.
Both compounds have been reported previously in the patent
literature with 2 used as a ‘‘solvent’’ for pharmaceutical or cosmetic
compositions, although few details are given.19Compound 1 is
crystalline and was characterised by X-ray crystallography.w
The crystal packing was examined by Hirshfeld surface analysis20
which showed the intermolecular interactions are dominated by
CHÁ Á ÁO hydrogen bonds to the polar carbonyl oxygen atom
(Fig. 1a) which is expected to possess a significant partial
negative charge in cyclic amides of this type (ca. À0.421).
In contrast, 2 is isolated as a viscous oil. Rigorous drying of
the compound under high vacuum does result in its crystal-
lisation as a plastic solid (see the ESIw) however it is highly
water soluble and on dissolution in water the oil re-forms. This
high affinity of 2 for water may be linked to the behaviour of
PVCap as a KHI and is likely to arise from the lack of strong
a Department of Chemistry, Durham University, South Road, Durham,
DH1 3LE, UK. E-mail: jon.steed@durham.ac.uk
b International Specialty Products, 1361 Alps Road, Wayne,
NJ 07470, USA. E-mail: omusa@ispcorp.com
c Department of Chemistry, School of Engineering and Physical
Sciences Heriot-Watt University, Edinburgh, EH14 4AS
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c1cc13556b
Scheme 1 Parent monomers, KHIs and model compounds.
Chem. Commun., 2011, 47, 9891–9893 9891
c
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because the OH bending mode in water obscures the carbonyl
region of the IR spectra. In dry acetonitrile the CQO stretch
in 2 occurs at 1638 cmÀ1 suggesting stronger hydrogen bonding
to the carbonyl group in the neat film than in aprotic solution,
consistent with the CHÁ Á ÁO hydrogen bonding observed in the
structure of 1. As D2O is added in solution in aliquots up to 500
molar equivalents the CQO band broadens and shifts to
1614 cmÀ1 (see the ESIw). In pure D2O the band occurs at
1609 cmÀ1. This data closely parallels the behaviour of
commercial PVCap (1637 cmÀ1 shifting to 1614 cmÀ1). Analogous
titration of 1 results in a shift and broadening of the two
carbonyl bands from 1651 and 1632 cmÀ1 to 1636 (shoulder)
and 1612 cmÀ1. This data show that both PVCap and the
model compounds interact strongly with water, with hydrogen
bonding to the polar carbonyl oxygen atom resulting in a
weakening of the CQO bond. The behaviour of compound 2
in particular closely parallels the commercial polymer. Analogous
titration with VP and PVP showed similar changes, which are
summarised in Table 1.
Fig. 1 (a) X-Ray structure of 1 showing one of the strong CHÁ Á ÁO
interactions, (b) X-ray molecular structure of 2.
hydrogen bond donor groups in 2 to match the strongly
hydrogen bond basic oxygen atom. Crystalline 2 was characterised
by synchrotron X-ray crystallography using beamline I19 at
Diamond. The structure has a remarkably low density of
1.162 g cmÀ1 even at À123 1C, in contrast to 1 (1.231 g cmÀ1
)
that seems linked to the very much weaker intermolecular
interactions which comprise only very long CHÁ Á ÁO contacts
(Fig. 2) reflecting the low hydrogen bond acidity of the
C(sp3)H groups. It is likely that this feature explains the highly
hydrophilic nature of 2, and hence PVCap.
Quantitative information regarding D2O binding by VP,
VCap and compounds 1 and 2 was obtained by 1H NMR
spectroscopic titration in dry acetonitrile-d3. The resulting
titration isotherms fit a combined 1 : 1 and 1 : 2 stoichiometric
model for 1 and 2 while a 1 : 1 model was adopted for the
monomers. Equilibrium constants were obtained by non-
linear least squares regression using the program HypNMR.
The resulting binding constants are given in Table 2. Overall,
the binding constants are relatively weak. Compounds 1 and
particularly 2 proved to bind a single water molecule some-
what more strongly than the monomers, although binding of
the second water molecule is weak and shows no enhancement
relative to the monomers. This data suggests that the dimeric
model compounds may posses complementary water binding
pockets. Binding constants for 2 may be underestimated due
to the compound’s hygroscopicity.
The interaction of both 1 and 2 with water in comparison
with a sample of commercial PVCap, and VCap and VP
monomers was examined using IR and NMR spectroscopy.
Previous IR spectroscopic studies on PVCap and PVP show
that the frequency of the amide I band in a dry film of PVCap
decreases on addition of up to 7 water molecules per monomer
unit.21,22 The amide I CQO stretching frequency for VP is
significantly higher than VCap (1701 vs. 1659 cmÀ1) indicating
more carbonyl double bond character in VP as a result of
strain in the 5-membered ring. For VCap the less strained
7-membered ring results in a significantly greater contribution
of the enolate resonance form and hence the VCap oxygen
atom is expected to be a particularly good hydrogen bond
acceptor. This difference is also reflected in data for PVP and
PVCap, 1685 vs. 1640 cmÀ1
.
The structure of the stable solution monohydrate complex
of 2 was probed by DFT calculations. The M06-2X functional
from the Truhlar family was used, in conjunction with the
6-311(d,p) basis augmented by an extra set of diffuse s and p
functions on the atoms involved in hydrogen bonding. Analytical
Hessians were computed to confirm minima. The calculated
structure of 2ÁH2O is shown in Fig. 3 and reveals that 2 adopts
a conformation that is highly complementary to water binding
with the water guest molecule forming two, strong,
IR spectroscopic measurements on 2 as a neat film show
that the CQO stretch occurs at 1628 cmÀ1 close to the value
for PVCap. The unsymmetrical 1 shows two CQO bands at
1639 and 1622 cmÀ1 in addition to an absorption at 1667 cmÀ1
assigned to the CQC stretching mode. The interaction of 1, 2,
VP, VCap, PVCap and PVP with water was monitored by
titration of D2O into a dry acetonitrile solution of the compounds.
Acetonitrile was chosen because it possesses only weak hydrogen
bond donor properties, while D2O was used instead of H2O
Table 1 IR spectroscopic titration data for the amide I band in VP,
VCap, 1, 2, PVP and PVCap with D2O (up to 500 molar equivalents)
in dry acetonitrile solution
n(CQO), cmÀ1
Neat
MeCN
MeCN + D2O
Compound
VP
Vcap
1
1701
1659
1639
1704
1662
1651
1632
1638
1682
1637
1667
1645
1636
1612
1614
1654
1614
1622
2
1628/1625a
1674/1685b
1621/1640b
PVP
PVCap
Fig. 2 Hirshfeld surface fingerprint plots20 (a) compound 1 showing
CHÁ Á ÁO interactions (arrows), (b) compound 2 in which the CHÁ Á ÁO
interactions are less pronounced.
a
b
1628–1630 cmÀ1 as an oil, 1625 cmÀ1 as a crystalline solid. Data
from ref. 21 and 22.
c
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Table 2 Water binding constants determined by 1H NMR spectro-
scopic titration
the development of water-water hydrogen bonded clusters
spanning the gap between carbonyl pairs (see the ESIw). This
bound water is likely to correlate with some of the ca. 6.5
molecules of non-freezable bound water per monomer unit in
PVCap.23
Compound
VCap
VP
1
2
Logb11
À1.16(3)
À1.30(3)
À0.44(7)
0.36
0.24(3)
1.74
K11/MÀ1
Logb12
0.07
0.05
In conclusion, IR data indicate that 2 behaves similarly to
PVCap in its mode of interaction with water. The interaction is
via OHÁ Á ÁO and CHÁ Á ÁO hydrogen bonding with 2 binding
more strongly to water as a result of a unique complementary
pocket that is likely to be a feature of commercial PVCap
KHI. Structural studies reveal a very low density for 2
suggesting a lack of self-complementarity results in its very
high hydrophilicity. The mode of action of PVCap as a KHI
via hydrogen bond acceptance at the oxygen atoms may be
related to the presence of ester carbonyls in acid impurities in
non-plugging oils.24
À1.45(9)
À1.06(3)
K12/MÀ1
0.09
0.05
We thank Diamond Light Source for synchrotron beam
time allocated to the regional team of Newcastle and Durham
Universities.
Fig. 3 DFT calculated structure of (a) 2ÁH2O showing pairwise
OHÁ Á ÁO and CHÁ Á ÁO hydrogen bonds and (b) 1ÁH2O.
symmetrical OHÁ Á ÁO interactions to the carbonyl groups while
accepting CHÁ Á ÁO hydrogen bonds from the methylene groups
of the VCap dimer receptor. The calculated structure of the
monohydrate of 1 shows that the water molecule adopts a
similar position in which it hydrogen bonds to both amide
oxygen atoms, although the shape of 1 is less complementary
to water and does not allow the formation of additional
CHÁ Á ÁO interactions in the minimum energy geometry.
Notes and references
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DFT calculations on dihydrates of 2 result in two structures
of very similar energy, one involving the same motif as that
shown in Fig. 3a with the second water molecule binding on
the opposite side of one of the carbonyl groups. The other
involves a directly waterÁ Á Áwater hydrogen bonded pair each
forming only one OHÁ Á ÁO interaction to the inhibitor mimic.
In each case complexation of the second water molecule would
be expected to be less energetically favourable than the first.
In order to test whether such water-binding motifs are
possible in PVCap, DFT calculations were carried out on
short segments of syndiotactic polymer with 6–8 repeat units
in the presence of varying numbers of water molecules. Water
molecules were found to hydrogen bond between pairs of
carbonyl oxygen atoms in a similar way to the model systems
shown in Fig. 3. In the presence of a small number of water
molecules each carbonyl group interacts with a single water
molecule to give water situated between alternating VCap
pairs. As the number of water molecules is increased the
unoccupied sites are filled to give a water between every
carbonyl pair (Fig. 4). Increasing the number of water molecules
beyond the number of sites in between carbonyl pairs results in
17 C. Moon, R. W. Hawtin and P. M. Rodger, Faraday Discuss.,
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Fig. 4 DFT calculated structure of a 8-monomer segment of PVCap
in the presence of six water molecules.
c
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Chem. Commun., 2011, 47, 9891–9893 9893