Monodisperse oligo(δ-valerolactones) and oligo(ε-caprolactones) with docosyl (C22) end-groups

José E. Báez *a, Kenneth J. Shea b, Philip R. Dennison b, Armando Obregón-Herrera c and José Bonilla-Cruz d
aDepartment of Chemistry, Division of Natural and Exact Sciences, University of Guanajuato (UG), Noria Alta S/N 36050, Guanajuato, Gto. Mexico. E-mail: jebaez@ugto.mx
bDepartment of Chemistry, University of California, Irvine, (UCI), Irvine, California, 92697-2025, USA
cDepartment of Biology, Division of Natural and Exact Sciences, University of Guanajuato (UG), Noria Alta S/N 36050, Guanajuato, Gto. Mexico
dCentro de Investigación en Materiales Avanzados S.C. (CIMAV-Unidad Monterrey), Av. Alianza Norte 202, PIIT, Autopista Monterrey-Aeropuerto Km 10, Apodaca, N.L., 66628 Mexico

Received 20th April 2020 , Accepted 17th June 2020

First published on 18th June 2020


Linear aliphatic oligoesters derived from δ-valerolactone (VL) and ε-caprolactone (CL) were synthesised by ring-opening polymerisation (ROP) using 1-docosanol (C22H45OH, C22OH) and aluminum isopropoxide [Al(OiPr)3] as initiator and catalyst, respectively. Monodisperse species such as monomers, dimers, trimers, and tetramers with terminal groups α-hydroxyl-ω-docosyl (C22)-(C22VL and C22CL) were isolated by flash column chromatography (FCC). Characterisation by MALDI-TOF and 1H NMR spectroscopy corroborated the chemical nature of the samples. This work represents the first time in the literature that monodisperse species derived from VL are isolated. The thermal properties of C22VL and C22VL showed a pattern suggesting that the crystallinity was proportional to the length of the chain. The presence of C22 groups promoted the nucleation of the crystalline domain in the monomers (C22VL1 and C22CL1), increasing their respective melting temperatures (Tm) relative to those of their non-monodisperse oligomers (C22PVL or C22PCL). Finally, monodisperse species and non-monodisperse oligomers were analysed by POM.


Introduction

Biodegradable polymers are of great contemporary interest due to their diverse potential applications, for example as environmentally friendly materials used in the substitution and reduction of non-biodegradable plastics or in the field of biomedicine.1 Poly(δ-valerolactone) (PVL) and poly(ε-caprolactone) (PCL) are two linear aliphatic polyesters of high value in this regard due to their biodegradable and biocompatible properties.2–4 A large number of studies have been dedicated to the chemical synthesis of PVL and PCL materials with a wide range of different number-average molecular weights (Mn) from oligomers to long chain polymers [Mn = 810– 232[thin space (1/6-em)]000].5–9 In this sense, oligomers derived from PVL or PCL are chemical species of major importance to polymer science, for example in the synthesis of diblock or triblock copolymers10,11 or macrodiols used as precursors of polyurethanes.11–14

Oligomeric species represent an interesting research topic that holds the key to understanding the effects of growth of the main chain of a macromolecule in terms of its structure–property relationships; in recent years oligomers such as oligo(ethylene glycol)15 and oligo(meth)acrylates16 have been isolated as monodisperse species. In the last lustrum, a series of contributions to separate oligomers with a lower dispersity, quasi-monodisperse, or monodisperse species by chromatography techniques such as flash column chromatography (FCC) has been reported.16–21 Besides, two different scientific groups led by Hawker19,20 and Junkers16–18 have published the use of automated FCC as a powerful instrument in the isolation of oligomers. It is particularly noteworthy that, although a large number of studies have been reported on the synthesis and characterisation of PVL and PCL,5–14 only a single report exists of the isolation of monodisperse species derived from PCL oligomers, namely a study from Hawker et al.22 whereby a series of monodisperse oligomers derived from poly(ε-caprolactone) (PCL) were synthesised using 6-hydroxycaproic acid as starting material and using tert-butyldimethylsilyl ether and benzyl ester protecting groups. The authors found that the lamellae thickness of PCL corresponded to 16 caprolactone units. On the other hand, no monodisperse oligomeric species derived from PVL have been reported.

PVL and PCL have an ester group and four and five methylene groups as part of their repeat units, respectively (Scheme 1). Usually, the synthesis of PVL and PCL proceeds by ring-opening polymerisation (ROP) of the corresponding lactone (δ-valerolactone (VL) or ε-caprolactone (CL), respectively).9,23,24 Existing literature reports are significantly (ca. 14-fold) more abundant for PCL than PVL.25 This can probably be attributed to the cost of the precursor monomers, as CL is roughly one-sixth the price of VL.26 Additionally, VL is more labile to be polymerised at room temperature by impurities with respect to CL, this is the reason that the VL is sold as technical grade (with a blend of oligomers) and CL as reagent grade (and easy to be stored at room temperature).26 PVL is more hydrophilic than PCL, Schacht and coworkers demonstrated that an essential parameter in the rate of degradation of polyesters depends on the chemical structure, where PVL was disintegrated more rapidly than PCL under an enzymatic degradability.27 Typically, the ROP of lactones involves the use of a metal-containing catalyst and an aliphatic alcohol or diol initiator.28,29 In previous work, Báez et al. studied the effect of different aliphatic substituents using aliphatic alcohols as initiators in the ROP of CL, and found that the impact of the linear alkyl end group on the crystallinity of PCL oligomers with a degree of polymerisation (DP) of 10–20 was negligible.30


image file: d0py00576b-s1.tif
Scheme 1 Synthesis of oligo(δ-valerolactone) (C22PVL) (top) and oligo(ε-caprolactone) (C22PCL) (bottom) with docosyl (C22) end-group catalysed by aluminum triisopropoxide [Al(OiPr3)] and 1-docosanol as initiator (C22OH).

In this work, we present the synthesis, isolation, and characterisation of monodisperse oligomeric species derived from VL and CL with a linear aliphatic terminal group, namely docosyl (C22). Oligomeric species from monomers to tetramers were isolated by simple FCC and then analysed by a range of techniques to understand the effect that the degree of polymerisation and the C22 groups have on the physical properties of the oligomer.

Experimental section

Materials

Anhydrous solvents were used in all reactions described herein. δ-Valerolactone (VL) and ε-caprolactone (CL) were supplied by Alfa Aesar and Aldrich, respectively. CL and VL were dried over calcium hydride (CaH2) for 24 h and distilled under reduced pressure before use. Aluminum triisopropoxide [Al(OiPr)3] was provided by Aldrich and used without purification. All polymerisation reactions were performed under an atmosphere of N2 using a Schlenk line. 1-Docosanol (C22OH) was supplied by Acros Organics. Deuterated solvents such as chloroform-d (CDCl3), benzene-d6 (C6D6), and toluene-d8 (C7D8) were provided by Cambridge Isotope Laboratories, Inc. and dried by molecular sieves before use or using sealed glass ampules. Thin-layer chromatography (TLC) was performed on percolated silica gel plates and using a Seebach staining reagent. Flash column chromatography (FCC) was conducted using 230–400 mesh silica gel. Toluene and ethyl acetate were used as the mobile phase during FCC.

Instruments

Nuclear magnetic resonance (NMR) spectroscopy. Solution state 1H and 13C spectra were recorded at room temperature or above on a Bruker DRX500 (1H: 500 MHz; 13C: 125 MHz) or AVANCE 600 (1H: 600 MHz 1H; 13C: 150 MHz) spectrometer, both with cryoprobes. Chloroform-d (CDCl3), benzene-d6, and toluene-d8 were used as solvents. Spectra were referenced to the residual solvent protons at 7.26, 7.16, and 7.09 ppm for CDCl3, benzene-d6, and toluene-d8, respectively, in the 1H NMR spectrum and the remaining solvent carbon nuclei at 77.0, 128.39, and 137.86 ppm for CDCl3, benzene-d6, and toluene-d8, respectively, in 13C NMR spectra. Fourier-transform infrared spectroscopy (FT-IR). FT-IR spectra were obtained with the attenuated total reflectance spectroscopy (ATR) technique on powder deposited over a diamond on zinc selenide (ZnSe) crystal in a PerkinElmer Spectrum One spectrometer. Differential scanning calorimetric (DSC). DSC was performed in a TA Instruments Q2000 apparatus. These scans (25–120 °C, 120 to −30 °C, and −30 to 120 °C) were performed by using a heating rate of 10 °C min−1 and cooling the instrument between runs under a nitrogen purge. The melting points (Tm) are given as the minimum of the endothermic transition, and the data presented are taken from the second heating scan. The degree of crystallinity (xi) for PCL was calculated from the endothermic peak area (ΔHPCL) by image file: d0py00576b-t1.tif, where image file: d0py00576b-t2.tif is the heat of fusion for perfectly crystalline PCL (135.3 J g−1).31 For most of the C22PVL or C22PCL samples, both docosyl and polyester segments are overlapping in the same endothermic band. Size exclusion chromatography (SEC). All polyester samples were dissolved in THF (5 mg/5 mL) heating at 37 °C for one hour and filtered with an 0.45 μm acrodisc®. The SEC instrument (Agilent) was equipped with a refractive index detector. Measurements were determined using a single column PLgel 5 μm Mixed-D (Agilent) at a flow rate of 1.0 mL min−1 with HPLC-grade THF. Polystyrene standards (Polymer Laboratories) were used for calibration. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) spectrometry. MALDI-TOF spectra were recorded in the reflectron mode by using an AB SCIEX TOF/TOF 5800 SYSTEM equipped with a nitrogen laser emitting at λ = 349 nm, an input bandwidth of = 1000 MHz with a 3 ns pulse width, and working in positive mode and with delayed extraction. 2,5-Dihydroxybenzoic acid (DHB) was used as matrix. For each type of matrix solution, a concentration of 10 mg mL−1 in THF as a solvent was used. C22PCL or C22PVL samples (3 mg mL−1) were dissolved in THF at room temperature, and then 10 μL of sample solution was mixed with 10 μL of the matrix solution (50/50, vol/vol) in an Eppendorf tube and mixed in a vortex. Different aliquots were placed on a stainless-steel plate, and the solvent was evaporated to make the film start the acquisition. Polarised optical microscopy (POM). POM micrographs were obtained using a Carl Zeiss optical microscope; photographs were taken using an iPhone SE. 1-Docosanol (C22OH) and oligomers were mounted on glass slides as thin films melted at 130 °C using a hot plate and applying manual pressure between the two slides containing the sample and a cover glass. The samples were cooled at room temperature before analysis. All samples were collected with a magnification of 40×.

Synthesis of α-hydroxyl-ω-docosyl poly(δ-valerolactone) C22-PVL (DPtheo = 6)

Inside a glovebox, 52.0 mg (0.2546 mmol) of aluminum isopropoxide Al(OiPr)3 (catalyst) was placed in a 50 mL Schlenk flask and adapted to a distillation system under an argon atmosphere. Next, the entire system was connected to nitrogen using a Schlenk line (N2/vacuum). Previously, 1-docosanol (initiator, C22OH, 653.2 mg, 2 mmol) was dissolved in 25 mL of THF and degassed, and then it was injected into the Schlenk flask containing Al(OiPr)3. The solution was stirred and distilled to favor the displacement of isopropanol from Al(OiPr3) by a transfer reaction32 with an excess of C22OH and produce a new aluminum alkoxide [Al(OC22)3] in situ. After the first distillation, a new volume of toluene (6 mL) was added and distilled as part of an azeotropic distillation between isopropanol and toluene; this step was repeated three times. Next, 25 mL of THF (solvent) was added under stirring until dissolution, and then 1.11 mL (12 mmol) of δ-valerolactone (VL, monomer, previously degassed) was injected into the solution (VL/C22OH molar ratio = 6). After 17 h at room temperature, the reaction was quenched and precipitated with an excess volume of cold methanol, stirred, filtered, and the powder was dried under vacuum overnight. A white powder was obtained (yield = 85%). Isolation of oligomers by flash column chromatography: 500 mg of C22PVL (DPtheo = 6) was dissolved in the minimum volume of toluene (5 mL) and added to a silica gel column with toluene used as mobile phase. Gradually, the fraction of toluene/ethyl acetate was increased to 90/10, 80/20 and 75/25. All of the fractions were analysed by thin-layer chromatography (TLC, mobile phase: toluene/ethyl acetate = 80/20) and visualising the spots using the Seebach staining reagent. The fractions were collected in test tubes, the solvent was evaporated by a rotary evaporator, and the resulting solid was dried overnight under vacuum oven. Fractions of unreacted C22OH [43 mg, wt% = 20.58%, mol% = 35.6% (mol%C22OH = 100%)], monomer C22VL1 [6 mg, wt% = 2.88%, mol% = 3.73%, (mol%C22OH = 50%, mol%CL = 50%], dimer C22VL2 [18 mg, wt% = 8.61%, mol% = 9.09%, (mol%C22OH = 33.33%, mol%CL = 66.66%)], trimer C22VL3 [45 mg, wt% = 21.53%, mol% = 19.12%, (mol%C22OH = 25%, mol%CL = 75%)], tetramer C22VL4 [40 mg, wt% = 19.13%, mol% = 14.65% (mol%C22OH = 20%, mol%CL = 80%)], and pentamer C22VL5 [57 mg, wt% = 27.27%, mol% = 18.35% (mol%C22OH = 16.6%, mol%CL = 83.3%)] were isolated. Additionally, the remaining product of the fractions of oligomer blends was collected (189 mg). NMR data at 40 °C: 1H NMR (500 MHz, C6D6, ppm). C22VL1 (Fig. 3a and Fig. S1): δ 4.04 (t, 2H, [e, –CH2–O–], C22), 3.26 (t, 2H, [a, –CH2–OH], VL1), 2.13 (t, 2H, [d, –CH2–CO–], VL1), 1.60 (quintet, 2H, [f, –CH2–CH2–O–], C22), 1.49 (quintet, 2H, [b, –CH2–CH2–OH], VL1), 1.36 (quintet, 2H, [c, –CH2–CH2–CH2–OH], VL1), 1.36 (m, 2H, [g, –CH2–], C22), 0.92 (t, 3H, [h, –CH3], C22). C22VL2 (Fig. 3b): δ 4.03 (t, 2H, [e, –CH2–O–], C22), 3.94 (t, 2H, [i, –CH2–CO], VL2), 3.30 (t, 2H, [a, –CH2–OH], VL2), 2.10 (t, 2H, [d, –CH2–CO–], VL2), 1.57 (quintet, 2H, [f, –CH2–CH2–O–], C22), 1.49 (quintet, 2H, [b, –CH2–CH2–OH], VL2), 1.40 (quintet, 2H, [c, –CH2–CH2–CH2–OH], VL2), 1.36 (m, 2H, [g, –CH2–], C22), 0.92 (t, 3H, [h, –CH3], C22). 13C NMR (125 MHz, C6D6, ppm): C22VL1 (Fig. S3). FT-IR: C22VL1 (Fig. S5).

Synthesis of α-hydroxyl-ω-docosyl poly(ε-caprolactone) C22-PCL (DPtheo = 2)

Inside a glovebox, 52.0 mg (0.2546 mmol) of aluminum isopropoxide Al(OiPr)3 (catalyst) was placed in a 50 mL Schlenk flask and adapted to a distillation system under an argon atmosphere. Next, the entire system was connected to nitrogen using a Schlenk line (N2/vacuum). Previously, 1-docosanol (initiator, 653.2 mg, 2 mmol) was dissolved in 25 mL of THF and degassed, and this was injected into the Schlenk flask containing Al(OiPr)3. The solution was stirred and distilled to favor the displacement of isopropanol from Al(OiPr3) by a transfer reaction32 with an excess of C22OH and produce a new aluminum alkoxide [Al(OC22)3] in situ. After the first distillation, more toluene (6 mL) was added and distilled as part of an azeotropic distillation between isopropanol and toluene; this step was repeated three times. Next, 25 mL of THF (solvent) was added under stirring until dissolution, and then 0.44 mL (4 mmol) of ε-caprolactone (CL, monomer, previously degassed) was injected into the solution (CL/C22OH molar ratio = 2). After 17 h at room temperature, the reaction was quenched and precipitated with an excess volume of cold methanol, stirred, filtered, and the powder was dried under vacuum overnight. A white powder was obtained (yield = 82%). Isolation of oligomers by flash column chromatography: 430 mg of C22PCL (DPtheo = 2) was dissolved in the minimum of toluene (5 mL) and added to a silica gel column with toluene used as mobile phase. Gradually, the fraction of toluene/ethyl acetate was increased to 90/10, 80/20 and 75/25. All of the fractions were analysed by thin-layer chromatography (TLC, mobile phase: toluene/ethyl acetate = 80/20) and visualising the spots using the Seebach staining reagent. The fractions were collected in test tubes, the solvent was evaporated by rotary evaporator, and the resulting solid was dried overnight under vacuum oven. Fractions of unreacted C22OH [50 mg, wt% = 25.64%, mol% = 34.9%, (mol%C22OH = 100%)], monomer C22CL1 [83 mg, wt% = 42.58%, mol% = 42.9% (mol%C22OH = 50%, mol%CL = 50%)], dimer C22CL2 [24 mg, wt% = 12.30%, mol% = 9.80% (mol%C22OH = 33.33%, mol%CL = 66.66%)], trimer C22CL3 [26 mg, wt% = 13.33%, mol% = 8.90% (mol%C22OH = 25%, mol%, CL = 75%)], and tetramer C22CL4 [12 mg, wt% = 6.15%, mol% = 3.50% (mol%C22OH = 20%, mol%CL = 80%)] were isolated. Additionally, the remaining product of the fractions of oligomer blends was collected (130 mg). NMR data at 40 °C: 1H NMR (500 MHz, CDCl3, ppm). C22CL1 (Fig. 4a and Fig. S2): δ 4.05 (t, 2H, [e, –CH2–O–], C22), 3.65 (t, 2H, [a, –CH2–OH], CL1), 2.31 (t, 2H, [d, –CH2–CO–], CL1), 1.66 (quintet, 2H, [d′, −CH2–CH2–CO–], CL1), 1.60 (quintet, 2H, [b, −CH2–CH2–OH], CL1), 1.59 (quintet, 2H, [f, –CH2–CH2–O–], C22), 1.40 (quintet, 2H, [c, –CH2–CH2–CH2–OH], CL1), 1.25 (m, 2H, [g, –CH2–], C22), 0.88 (t, 3H, [h, –CH3], C22). C22CL2 (Fig. 4b): δ 4.06 (t, 2H, [e, –CH2–O–], C22), 4.05 (t, 2H, [i, –CH2–O–], CL2), 3.65 (t, 2H, [a, –CH2–OH], CL2), 2.31 (t, 2H, [d, –CH2–CO–], CL2), 1.66 (quintet, 2H, [d′, –CH2–CH2–CO–], CL2), 1.60 (quintet, 2H, [b, –CH2–CH2–OH], CL2), 1.59 (quintet, 2H, [f, –CH2–CH2–O–], C22), 1.40 (quintet, 2H, [c, –CH2–CH2–CH2–OH], CL2), 1.25 (m, 2H, [g, –CH2–], C22), 0.88 (t, 3H, [h, –CH3], C22). 13C NMR (125 MHz, CDCL3, ppm): C22CL1 (Fig. S4). FT-IR: C22CL1 (Fig. S6).

Results and discussion

Oligomers derived from aliphatic polyesters were synthesised by ring-opening polymerisation (ROP) of ε-caprolactone (CL) or δ-valerolactone (VL), in each case using aluminum triisopropoxide and 1-docosanol (C22OH) as catalyst and initiator, respectively (Scheme 1). After each reaction, a considerable content of unreacted C22OH was observed by NMR. To isolate the C22OH from the crude of reaction, different solvents were tested for the thin layer chromatography (TLC). Eventually, a toluene/ethyl acetate solvent system (Experimental section) was effective in the separation of the spots. Additionally, a series of spots attributed to oligoesters derived from C22VL and C22CL were visualised. Thus, using flash column chromatography (FCC), a series of monodisperse oligoesters derived from C22VL and C22CL were collected and isolated. Using this methodology, the species from monomer to tetramer were separated and characterised for each oligoester. To corroborate the chemical nature of the oligoesters C22VL and C22CL isolated previously, an analysis by MALDI-TOF spectrometry was performed. In Table 1, signals corresponding to a series of monodisperse species derived from C22VL1–4 and C22CL1–4 and doped with sodium (Na+) and potassium (K+) are tabulated, whereby the differences between the theoretical and experimental values are less than 1 g mol−1, indicating good agreement. Fig. 1 shows, MALDI-TOF spectra for a series of oligoesters, wherein a single peak doped with sodium and potassium is evidenced for each oligoester, indicating the presence of monodisperse species. Complementary, in Fig. 2, for the monomer species (C22VL1 and C22CL1) a comparison between the experimental and simulated spectra is illustrated, where each pair showed a good agreement.
image file: d0py00576b-f1.tif
Fig. 1 MALDI-TOF spectra of monodisperse species derived from C22VL (a–c) and C22CL (d–f) (Table 1).

image file: d0py00576b-f2.tif
Fig. 2 Experimental MALDI-TOF mass spectra of the monomer species [C22VL1K+ (top, left) (Fig. 1a) and C22CL1K+ (top, right) (Fig. 1d)] and isotopic distribution calculated for DP = 1 [C27H54O3K+ (C22VL1K+, bottom, left) and C28H56O3K+ (C22CL1K+, bottom, right)] in http://www.chemcalc.org.36
Table 1 Results of MALDI-TOF mass spectrometry for monodisperse species isolated by flash column chromatography (FCC) and derived from δ-valerolactone (VL) and ε-caproctone (CL) with terminal docosyl [CH3(CH2)21–] (C22) groups
No. Sample Precursor Species MW(theo) (g mol−1) Theoretical a (Na+) Experimental b (Na+) Theoretical a (K+) Experimental b (K+) Purity c (%)
a Theoretical value calculated from molecular weight (MW) of sample + atomic weight (AW) of Na+ or K+. b Experimental value obtained by MALDI-TOF spectrometry. c Obtained by MALDI-TOF. d C22VL5 was isolated with a trace of C22VL4 (Fig. S7). e C22CL4 was isolated with a significant amount of C22CL3 (Fig. S8).
1 C22VL1 VL Monomer 426.72 449.70 449.23 465.81 465.23 100
2 C22VL2 VL Dimer 526.84 549.82 549.31 565.93 565.25 99
3 C22VL3 VL Trimer 626.96 649.94 649.31 666.05 665.30 99
4 C22VL4 VL Tetramer 727.08 750.06 749.42 766.17 765.35 98
5 C22VL5 VL Pentamerd 827.20 850.18 849.46 866.29 865.40 96
6 C22CL1 CL Monomer 440.74 463.72 463.29 479.83 479.30 99
7 C22CL2 CL Dimer 554.88 577.86 577.34 593.97 593.32 99
8 C22CL3 CL Trimer 669.02 692.00 691.44 708.11 707.43 99
9 C22CL4 CL Tetramere 783.16 806.14 805.55 822.25 821.45 75


Another technique to visualise the growth in the main chain of the oligoesters is 1H NMR spectroscopy. As shown in Fig. 3, 1H NMR spectra of oligoesters derived from C22-VL indicated the incorporation of docosyl (C22) and hydroxyl (–OH) terminal groups of the monomer (C22-VL1), dimer (C22-VL2), trimer (C22-VL3) and tetramer (C22-VL4). For the case of C22VL1 (Fig. 3a), signals for the methyl group of the C22 moiety [h, CH3, δ 0.92], and the methylene adjacent to the hydroxyl group [a, CH2, δ 3.26] were observed. The relative ratio of terminal groups h to a is ca. 3[thin space (1/6-em)]:[thin space (1/6-em)]2. Usually, the degree of polymerisation (DP) can be calculated by 1H-NMR spectroscopy, and is termed DPNMR. In our case, in Fig. 3a, the peaks d and a indicate the α (CH2–CO) and δ (CH2–OH) carbons of the monomer species and have relative intensities of 1[thin space (1/6-em)]:[thin space (1/6-em)]1 (Fig. S1), consistent with the presence of a monomer species. In the case of the dimer (Fig. 3b), the signal d is more complicated due to an overlapping of two triplets at the same chemical shift; additionally, a new peak (i) was observed, attributed to the δ carbon attached to another VL species; both peaks are evidence of the growth from monomer (Fig. 3a) to dimer (Fig. 3b). Complementary, in Fig. 3a–d, a gradual variation in the chemical shift from upfield to downfield of the methylene “a” adjacent to the hydroxyl group (CH2OH) is observed. This effect is attributed to the intermolecular hydrogen bonding between the hydroxyl group and the carbonyl group (CH2O–H⋯O[double bond, length as m-dash]C), where the probability that its interaction becomes higher is when the repetitive unit increases. On another side, the methylene “d” is α (Fig. 3a–d) to the carbonyl group (CH2C[double bond, length as m-dash]O), and d exhibited a displacement to upfield. In previous contributions,33–35 this phenomenon was observed, where an interaction between the carbonyl group and the benzene generates a high-field shift for the methylene group adjacent to the carbonyl group. This effect has been attributed to the solute-solvent interactions by dipole–dipole induced and van der Waals forces between C[double bond, length as m-dash]O and benzene deuterated (C6D6).33–35 The previous effect on the chemical shift was visualised only in the presence of C6D6 (magnetic anisotropy, Fig. 3) as a solvent, but absent in CDCl3 (Fig. 4). Thus, the molecular weights of the C22VL oligoesters previously determined by MALDI-TOF were corroborated by a second technique (1H NMR; Fig. 3), showing good agreement (Table S1).


image file: d0py00576b-f3.tif
Fig. 3 1H NMR (500 MHz) spectra in C6D6 at 40 °C of selected monodisperse oligomers derived from δ-valerolactone (VL) with terminal docosyl (C22) groups and isolated by flash column chromatography (FCC), (a) monomer C22VL1, (b) dimer C22VL2, (c) trimer C22VL3, and (d) tetramer C22VL4 (Table 1).

image file: d0py00576b-f4.tif
Fig. 4 1H NMR (500 MHz) spectra in CDCl3 at 40 °C of different monodisperse oligomers derived from ε-caprolactone (CL) with terminal docosyl (C22) groups and isolated by flash column chromatography (FCC), (a) monomer C22CL1, (b) dimer C22CL2, and (c) trimer C22CL3, and (d) tetramer C22CL4 (Table 1).

The samples of C22VL dissolved in CDCl3 suggested some depolymertisation, due to detection of the VL monomer by 1H NMR spectroscopy, this effect was attributed to the presence of acid (DCl) in CDCl3 that can initiate an intramolecular transesterification to generate the VL monomer (Fig. S9). To prevent C22VL depolymerisation, deuterated benzene (C6D6) was used (Fig. 3) instead of CDCl3. Additionally, SEC measurements using THF as solvent showed a unimodal distribution for monodisperse species (Fig. S10 and Table S2, ESI).

Fig. 4 shows 1H NMR spectra for monodisperse species derived from C22-CL, such as monomer, dimer, trimer, and tetramer, where a gradual increase in the integral peaks attributed to CL unit (b–d, d′ and i) indicated the growth from monomer to tetramer. The DPNMR for both species C22VL and C22CL showed excellent agreement with respect to DPtheo (Fig. 5).


image file: d0py00576b-f5.tif
Fig. 5 Profile of the molecular weight (MW) of monodisperse oligomeric species derived from C22VL and C22CL isolated by flash column chromatography (FCC) and detected by 1H NMR (Fig. 3 and 4, Table S1).

The use of the docosyl (C22) terminal group has three key effects. The first is the formation of an ester group instead of a carboxylic acid group; usually, hydroxy acid species such as 6-hydroxycaproic acid [HO(CH2)5CO2H] can undergo self-condensation,37 resulting in a mixture of oligomers.38 An alternative method to prevent this self-condensation is to use a C22 ester group as a protecting group. Hawker et al.22 has reported the use of tert-butyldimethylsilyl ethers and benzyl esters as protecting groups of CL oligomers. The second effect is that the C22 terminal group provides a better separation of the spots in the TLC plate than ethyl groups (C2) for these oligoesters. The third reason is due to the crystallization of a long aliphatic chain such as C22 end group that induces a melting point in all the monodisperse oligomeric samples.

Table 2 compiles, the thermal properties of the monodisperse C22VL and C22CL species. Usually, the melting temperature (Tm) of poly(δ-valerolactone) (PVL) and poly(ε-caprolactone) (PCL) is ca. 60 °C.39,40 The melting point of C22OH is 73 °C.10 The Tm values for C22VL and C22CL were in the ranges 54–61 °C and 48–61 °C, respectively. It is well known that the enthalpy of fusion (ΔHm) is proportional to the crystalline domain of a polymer sample, thus from, comparison of the profiles of ΔHm for C22VL and C22CL, it is evident that the values of ΔHm for C22CL are higher than C22VL. Thus, the crystallinity of C22CL is significant in comparison to C22VL species. The ΔHm for the monodisperse species is attributed to the C22 group and the oligoester. After the subtraction of that for C22, the enthalpy of the monodisperse species (VL or CL) is proportional to the length of the chain, from monomer to tetramer (Fig. 6). However, a singularity or exception was observed for C22VL2; studies to understand this are currently underway in our laboratory.


image file: d0py00576b-f6.tif
Fig. 6 Effect of the molecular weight (MW) on the enthalpy of fusion (ΔHm) and melting temperature (Tm) of monodisperse oligomers derived from (a) C22VL and (b) C22CL.
Table 2 Thermal properties of monodisperse species derived from C22-VL and C22-CL isolated by flash column chromatography (FCC)
No. Sample Precursor Species C22 (wt. %) Ester (wt. %) T m (°C) ΔHma (J g−1) ΔHmPVLa,b (J g−1) ΔHmPCLa,c (J g−1) x i (%)
a Obtained by differential scanning calorimetry (DSC), second scan. b Calculated by the equation ΔHmPVL = (ΔHm)·(xPVL), where xPVL represents the weight fraction of PVL in the oligomer. c Calculated by the equation ΔHmPCL = (ΔHm)·(xPCL), where xPCL represents the weight fraction of PCL in the oligomer. d Analysed according to the equation image file: d0py00576b-t3.tif, where image file: d0py00576b-t4.tif is the enthalpy of fusion to the 100% crystalline PCL with a value of 135.3 J g−1.31 e Minor peak. f Major peak. g A single peak was observed.
1 C22VL1 VL Monomer 76 24 54e, 59f 207 49.6
2 C22VL2 VL Dimer 62 38 24e, 39e, 54f 100 38.0
3 C22VL3 VL Trimer 52 48 58g 171 82.0
4 C22VL4 VL Tetramer 45 55 59g 156 85.8
5 C22VL5 VL Pentamer 39 61 61g 174 106.1
6 C22CL1 CL Monomer 74 26 61g 222 57.7 42
7 C22CL2 CL Dimer 59 41 54g 205 84.0 62
8 C22CL3 CL Trimer 49 51 49g 184 93.8 69
9 C22CL4 CL Tetramer 41 59 48g 189 111.5 82


The monodisperse species previously described were used to compare them with non-discrete oligomers/polymers (ES1-2, ESI) to understand the differences in terms of their physical properties. In Fig. 7, the thermograms illustrate the differences between a pair of oligomers derived from PVL (C22-PVL5.2, DPNMR = 5.2) and PCL (C22-PCL6.8, DPNMR = 6.8) (Table S3) and their corresponding monodisperse species such as monomers (C22-VL1 and C22-CL1) (Table 2). The two oligomers (C22-PVL5.2 and C22-PCL6.8) exhibited lower Tm values than monomers (C22-CL1 and C22-VL1). This effect can be explained by three considerations: (1) in the monomers, the hydroxyl terminal group can participate in significant hydrogen bonding interactions in the solid state increasing the Tm with respect to the oligomers, (2) the crystalline domain of the C22 segment in the monomers (74–76 wt%) has a significant contribution relative to those of oligomers (30–35 wt%), and (3) both monomer species (C22-VL1 and C22-CL1) are pure substances; a pure substance usually has a higher Tm than a mixture of different species, such as the oligomers derived from C22-PVL5.2 and C22-PCL6.8.


image file: d0py00576b-f7.tif
Fig. 7 DSC thermograms for species derived from (a) VL [oligomer (C22PVL5.2) (Table S3) and monomer (C22VL1) (Table 2)] and (b) CL [oligomer (C22PCL6.8) (Table S3) and monomer (C22CL1) (Table 2)].

Using polarised optical microscopy (POM) (Fig. 8), a series of samples were prepared by melting and cooling to room temperature, allowing visualization of their physical forms. In the case of C22OH (Fig. 8a), a spherulite was observed. When the C22 segment was part of the monomer (Fig. 8b and e) or dimer (Fig. 8c and f), the size of the spherulite decreased. Additionally, the spherulites in the oligoester C22PVL5.2 and C22PCL6.8 (Fig. 8d and g) were small in size. This evidence indicates that the size of the spherulites is dependent on the relative C22 content, suggesting that the C22 segment can act as a nucleation agent, improving the crystallinity in the monodisperse species; In a previous publication it was demonstrated that C22 units promoted the nucleation of PCL.10


image file: d0py00576b-f8.tif
Fig. 8 Polarized optical microscopy (POM, magnification: 40×) of (a) C22OH (1-docosanol), (b) C22VL1 (monomer), (c) C22VL2 (dimer), (d) C22PVL5.2 (oligomer), (e) C22CL1 (monomer), (f) C22CL2 (dimer), and (g) C22PCL6.8 (oligomer) (Table 2 and S3). Black bar = 50 μm.

In the case of oligoesters (C22-PVL5.2 and C22-PCL6.8), the dispersity (ĐM) is an additional factor to consider as a cause of the observed decrease in size. The size of the spherulites of the monomer species (C22VL1 and C22CL1) with respect to the oligoesters was dependent on the Tm detected by DSC. Thus, large spherulite provides a higher Tm because the diffusion of heat is more accessible in smaller spherulites than larger ones.

Conclusions

In summary, linear aliphatic oligoesters derived from δ-valerolactone (VL) and ε-caprolactone (CL) were synthesised by ring-opening polymerisation (ROP) of VL and CL using 1-docosanol (C22OH) and aluminum isopropoxide [Al(OiPr)3] as initiator and catalyst, respectively. By simple flash column chromatography (FCC), a series of nine different types of monodisperse oligo(VL) and oligo(CL) species were isolated. MALDI-TOF and 1H-NMR spectra confirmed the chemical nature of the monodisperse species from monomer to pentamer for oligo(VL) and from monomer to tetramer for oligo(CL). This work represents the first time in the literature that monodisperse species derived from VL are isolated. The enthalpy of fusion (ΔHm) of the monodisperse oligoesters (C22-VL or C22-CL) was found to be proportional to the length of chain, from monomer to tetramer. The comparison of monodisperse monomer species with oligoesters exposed significant differences in terms of thermal properties, such as their melting temperatures (Tm). The size of the spherulites was found to be dependent on the content of the docosyl group (C22), suggesting that C22 acts as a nucleation agent.

Additionally, previous reports have indicated that C22OH inhibits a broad spectrum of lipid-enveloped viruses. Thus, C22OH has been used as an active ingredient against the herpes labialis caused by herpes simplex virus (HSV).41,42 In this sense, the testing of our monodisperse species (C22-VL and C22-CL) as potential antiviral molecules is underway in our laboratory and will be reported in a future contribution. Finally, a systematic study of monodisperse species and oligomers as compatibilizer agents of polymer blends is also part of our interest in the laboratory.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

J.E.B. thanks CONACYT Ciencia Básica for the grant “Proyecto SEP/284893” and DAIP CIIC 2019 (UG) “Proyecto 030/2019”. The authors thank the Laboratorio Nacional de Caracterización de Propiedades Fisicoquímicas y Estructura Molecular (LACAPFEM UG-UAA-CONACYT) at the University of Guanajuato (UG), and Patricia Cerda Hurtado (CIMAV-Unidad Monterrey) for the acquisition of the SEC chromatograms.

Notes and references

  1. Q. Liu, L. Jiang, R. Shi and L. Zhang, Prog. Polym. Sci., 2012, 37, 715–765 CrossRef CAS .
  2. N. U. Dharmaratne, T. M. M. Jouaneh, M. K. Kiesewetter and R. T. Mathers, Macromolecules, 2018, 51, 8461–8468 CrossRef CAS .
  3. I. Khan, R. Nagarjuna, J. R. Dutta and R. Ganesan, ACS Omega, 2019, 4, 2844–2852 CrossRef CAS PubMed .
  4. F. Le Devedec, H. Boucher, D. Dubins and C. Allen, Mol. Pharmaceutics, 2018, 15, 1565–1577 CrossRef CAS PubMed .
  5. M. Tarnacka, A. Dzienia, P. Maksym, A. Talik, A. Zięba, R. Bielas, K. Kaminski and M. Paluch, Macromolecules, 2018, 51, 4588–4597 CrossRef CAS .
  6. M. Li, S. Behzadi, M. Chen, W. Pang, F. Wang and C. Tan, Organometallics, 2019, 38, 461–468 CrossRef CAS .
  7. K. Duale, M. Zięba, P. Chaber, D. J. Di Fouque, A. Memboeuf, C. Peptu, I. Radecka, M. Kowalczuck and G. Adamus, Molecules, 2018, 23, 2034 CrossRef PubMed .
  8. P. Lewinski, J. Pretula, K. Kaluzynski, S. Kaźmierski and S. Penczek, J. Catal., 2019, 371, 305–312 CrossRef CAS .
  9. X. Wang, J. L. Bronsmer, A. Thevenon and P. L. Diaconescu, Organometallics, 2015, 34, 4700–4706 CrossRef CAS .
  10. J. E. Báez, R. Zhao and K. J. Shea, Ind. Eng. Chem. Res., 2017, 56, 10366–10383 CrossRef .
  11. T. Saito, Y. Aizawa, K. Tajima, T. Isono and T. Satoh, Polym. Chem., 2015, 6, 4374–4384 RSC .
  12. J. E. Báez, A. Marcos-Fernández, R. Navarro, C. García, A. Ramírez-Hernández and K. J. Moreno, J. Polym. Res., 2019, 26, 32 CrossRef .
  13. Z. Ma, Y. Hong, D. M. Nelson, J. E. Pichamuthu, C. E. Leeson and W. R. Wagner, Biomacromolecules, 2011, 12, 3265–3274 CrossRef CAS PubMed .
  14. I. M. Arcana, B. Bundjali, M. Hasan, M. A. Zulfikar and K. Hariyawati, Polym. Int., 2011, 60, 1535–1540 CrossRef CAS .
  15. A. M. Wawro, T. Muraoka and K. Kinbara, Polym. Chem., 2016, 7, 2389–2394 RSC .
  16. J. J. Haven, J. De Neve, A. C. Villavicencio and T. Junkers, Polym. Chem., 2019, 10, 6540–6544 RSC .
  17. J. De Neve, J. J. Haven, S. Harrison and T. Junkers, Angew. Chem., Int. Ed., 2019, 58, 13869–13873 CrossRef CAS PubMed .
  18. J. J. Haven and T. Junkers, Polym. Chem., 2019, 10, 679–682 RSC .
  19. J. Lawrence, S.-H. Lee, A. Abdilla, M. D. Nothling, J. M. Ren, A. S. Knight, C. Fleischmann, Y. Li, A. S. Abrams, B. V. K. J. Schmidt, M. C. Hwaker, L. A. Connal, A. J. McGrath, P. G. Clark, W. R. Gutekunst and C. J. Hawker, J. Am. Chem. Soc., 2016, 138, 6306–6310 CrossRef CAS PubMed .
  20. J. M. Ren, J. Lawrence, A. S. Knight, A. Abdilla, R. B. Zerdan, A. E. Levi, B. Oschmann, W. R. Gutekunst, S.-H. Lee, Y. Li, A. J. McGrath, C. M. Bates, G. G. Qiao and C. J. Hawker, J. Am. Chem. Soc., 2018, 140, 1945–1951 CrossRef CAS PubMed .
  21. N. S. Vail, C. Stubbs, C. Biggs and M. I. Gibson, ACS Macro Lett., 2017, 6, 1001–1004 CrossRef CAS PubMed .
  22. K. Takizawa, C. Tang and C. J. Hawker, J. Am. Chem. Soc., 2008, 130, 1718–1726 CrossRef CAS PubMed .
  23. R. R. Gowda, D. Chakraborty and V. Ramkumar, Polymer, 2010, 51, 4750–4759 CrossRef CAS .
  24. R. R. Gowda, D. Chakraborty and V. J. Ramkumar, Organomet. Chem., 2011, 696, 572–580 CrossRef .
  25. Macromolecules, ACS Publications. (2020). [online] pubs.acs.org. Available at: https://pubs.acs.org/journal/mamobx [accessed June 2020].
  26. Sigma-Aldrich is now Merck (2020). [online] Available at: https://www.sigmaaldrich.com [accessed June 2020].
  27. V. Toncheva, A. Van den Bulcke, E. Schacht, J. Mergaert and J. Swings, J. Environ. Polym. Degrad., 1996, 4, 71–83 CrossRef CAS .
  28. H. Plommer, J. N. Murphy, L. N. Dawe and F. M. Kerton, Inorg. Chem., 2019, 58, 5253–5264 CrossRef CAS PubMed .
  29. Q. Hu, S. Jie, P. Braunstein and B.-G. Li, J. Organomet. Chem., 2019, 882, 1–9 CrossRef CAS .
  30. J. E. Báez, A. Marcos-Fernández and P. Galindo-Iranzo, Polym.-Plast. Technol. Eng., 2011, 50(8), 839–850 CrossRef .
  31. V. Crescenzi, G. Manzini, G. Calzolari and C. Borri, Eur. Polym. J., 1972, 8, 449–463 CrossRef CAS .
  32. A. Duda, Macromolecules, 1996, 29, 1339–1406 CrossRef .
  33. Y. Ichikawa and T. Matsuo, Bull. Chem. Soc. Jpn., 1967, 40, 2030–2034 CrossRef CAS .
  34. M. A. Wendt, J. Meiler, F. Weinhold and T. C. Farrar, Mol. Phys., 1998, 93, 145–151 CrossRef CAS .
  35. J. S. Lomas, Magn. Reson. Chem., 2016, 54, 28–38 CrossRef CAS PubMed .
  36. L. Patiny and A. Borel, J. Chem. Inf. Model., 2013, 53, 1223–1228 CrossRef CAS PubMed .
  37. E. Gabirondo, A. Sangroniz, A. Etxeberria, S. Torres-Giner and H. Sardon, Polym. Chem., 2020, accepted manuscritpt.
  38. J. E. Báez, A. Martínez-Richa and A. Marcos-Fernández, Macromolecules, 2005, 38, 1599–1608 CrossRef .
  39. M. Aubin and R. E. Prud'homme, Polymer, 1981, 22, 1223–1226 CrossRef CAS .
  40. R. F. Storey and D. C. Hoffman, Makromol. Chem., Macromol. Symp., 1991, 42, 185–193 CrossRef .
  41. E. De Clercq and G. Li, Clin. Microbiol. Rev., 2016, 29, 695–747 CrossRef PubMed .
  42. D. H. Katz, J. F. Marcelletti, M. H. Khalil, L. E. Pope and L. R. Katz, Proc. Natl. Acad. Sci. U. S. A., 1991, 88, 10825–10829 CrossRef CAS PubMed .

Footnote

Electronic supplementary information (ESI) available. See DOI: 10.1039/d0py00576b

This journal is © The Royal Society of Chemistry 2020