Star-shaped poly(N-vinylcaprolactam) and copolymerscgiqtectijuana.mx/wp-content/uploads/2019/02/STAR-PNVCL-POLYMER… · Star-shaped poly(N-vinylcaprolactam) and copolymers High density

Centro de Graduados e Investigación en Química, Instituto Tecnológico

de Tijuana.

A. P. 1166. Tijuana, B. C. 22000, México. E-mail: [email protected]

Norma Aidé Cortez-Lemus, 2019

Star-shaped poly(N-vinylcaprolactam) and copolymers

mailto:[email protected]

❖High density of internal and peripheral functional groups

compared to linear polymers of similar molecular weight

❖Synthesis of star polymers with a precise number of arms

❖The star polymers exhibit lower solution viscosity in dilute

solutions

❖Smaller hydrodynamic volume

❖Amphiphilic star block copolymers can encapsulate

efficiently drugs

Importance of the study of star-shaped

polymers

Kowollik, B. C.; Davis, P. T.; Stenzel, H. M. Aust. J. Chem. 2006,

59, 719-727.

Comparison of star synthesis using the core-first

technique using the Z-group (left) and R-group (right)

approaches.

G. D. García-Olaiz, K. A. Montoya-Villegas, A. Licea-Claverie, N. A. Cortez-Lemus. Synthesis andcharacterization of four- and six-arm star-shaped poly(ε-caprolactone)-b-poly(N-vinylcaprolactam): Micellar and core degradation studies. Reactive & Functional Polymers2015, 88, 16-23.

PNVCLPEGPEHA

(PVAc-b-(PNVCL-co-PNVP))6

(PNVCL-co-PNVP)6

(PNVCL)6

((PNVCL-co-PNVP)-b-PVAc)6

(PNVCL-b-PVAc)6

Poly(N-vinylcaprolactam) (PNVCL)

Poly(N-isopropylacrylamide) (PNIPAM)

Thermally responsivepolymers

LCST ~32 °CLCST ~30-50 °C

C=O ---- H-N

Internal hydrogen-bond:

Flory–Huggins type I

Flory–Huggins type II

Biocompatible

Thermosensitive polymers

Influence of End Groups on aqueous

properties of thermosensitive polymers

The LCST decreased or increased in thermosensitive polymers having

hydrophobic or hydrophilic end groups.

Solubility

Strong influence of end-groups on activity and cytotoxicity in

antimicrobials polymers.




Fig. 1. 1H NMR spectra (200 MHz) of six-arm star-shaped block copolymers with different molarcompositions. a) Mn,GPC=75,300 g/mol and b) Mn,GPC=26,900 g/mol.


Fig. 6. Hydrodynamic diameter of micellar aggregates determined by DLS at 25 °C (c = 1 mg/mL).

Fig. 7. LCST determined by DLS showingaggregation (samples S(PCL20-b-PNVCL69)4,S(PCL19-b-PNVCL75)6 and S(PCL19-b-PNVCL27)6 ora decrease in the hydrodynamic diameterS(PCL19-b-PNVCL13)6 in the micelle above theLCST.

Fig. 4. Representative images for micellescorresponding to sample S(PCL10-b-PNVCL46)4. a) SEM images of micelles (c =0.013 mg/mL), b) AFM image of a deposit ona mica substrate of an aqueous dispersion ofmicelles (c = 0.02 mg/mL). The solventdisplacement method was used in thepreparation of the micelles.

Fig. 5. AFM images of deposits of aqueousdispersions of micelles obtained from six-armstar(PCL-b-PNVCL) block copolymers on a micasubstrate. a) Sample S(PCL19-b-PNVCL75)6 andb) Sample S(PCL19-b-PNVCL13)6. The solventdisplacement method was used in thepreparation of the micelles.

a) b)

a) b)

Synthesis and characterization of “living” star-shaped

poly(N-vinylcaprolactam) with four arms and carboxylic

acid end-groups

Norma A. Cortez Lemus, Angel Licea-Claverie. J. Polym. Sci., Part A: Polym. Chem., 2016, 54,2156-2165. DOI: 10.1002/pola.28086.

Synthesis of tetra-functional RAFT agent functionalized with carboxylic acid end groups.

RAFT AGENT 1

RAFT AGENT 1


FIGURE 3 FT-IR spectra of a) CTA-1, b) star-shaped PNVCL-COOHpolymers and c) star-shaped S(PNVCL-b-PEHA) copolymers

1.502.002.503.003.504.00

d

d

a

a

b

b

c e

ce

f g

f f

g

ppm

ppm

10.0010.5011.0011.50

h

h

1H NMR spectra (400 MHz) of tetra-functional CTA-1 with carboxylic acid end groups

FIGURE 4 1H NMR (400 MHz) of star-shaped PNVCL-COOH polymers (sample S(PNVCL47)4)

Table 1 Results for RAFT polymerization of NVCL in p-dioxane at 65 ˚C for 36 h in the

presence of CTA-1.a

Entry Sample [NVCL]o: [CTA]o

Conv.b

(%) Mn theor

c Mn GPC

(g/mol)d

Ðe Mn UV-vis

f

1 S(PNVCL18)4 108:1 53 9,200 10,000 1.12 8,800

2 S(PNVCL47)4 246:1 45 16,621 26,000 1.05 21,200

3 S(PNVCL68)4 540:1 49 38,000 38,000 1.15 43,100

4 S(PNVCL94)4 700:1 41 41,100 52,000 1.02 53,500

5 S(PNVCL122)4 900:1 52 64,100 66,300 1.03 84,000

a[NVCL]= 4.8 mol/L.

bDetermined gravimetrically.

cCalculated using eqn Mn theo= MCTA + conversion (MNVCL[NVCL]o/[CTA]o)

d,eBy GPC in THF with RI detector using polystyrene linear standards for calibration and using dn/dc

0.109 (mL/g) for PNVCL.28

fCalculated by end group analysis of UV band (trithiocarbonate absorbance at λ 307 nm, employing ε of the CTA-1).


DLS measurements. Effects of molecular weight on the LCST of star PNVCL-COOH polymers determined by DLS (c = 1 mg/mL).


DLS measurements. Effects of molecular weight on the LCST ofstar PNVCL-COOH polymers (c = 1 mg/mL)


FIGURE 10 Effect of concentration on the LCST of star PNVCL-COOHpolymers (sample S(PNVCL47)4, Table 1, Mn GPC=26,000 g/mol).


ppm0.01.02.03.04.05.0

a

bc,i

d,e,h,j

f

g

a

d

cb

e ee

fg

g

h i

j

k

kkk

k

1H-NMR (400 MHz) spectrum of star-shaped PNVCL-b-PEHA-COOH copolymer in CDCl3

FIGURE 8 DLS measurements (c = 1 mg/mL). Hydrodynamic diameter of S(PNVCL)polymer (Mn GPC=66,300 g/mol) and hydrodynamic diameter of micellar aggregatesfrom S(PNVCL-b-PEHA) copolymer (Mn GPC=69,200 g/mol);


PNVCLPEGPEHA

CTA trithiocarbonate type

N. A. Cortez Lemus and A. Licea-Claverie, Aust. J. Chem. 2017, 70, 1291-1301.





(PNVCL-b-PEHA-b-PEG)6

PNVCLPEGPEHA

Triblock copolymer Micellar aggregate


Aggregates in aqueous solution from star (PNVCL-

b-PEHA-b-PEG)6 triblock copolymer


Figure 12 Drug release from thermoresponsive star polymeric aggregates containing MTX, a) 33 °C and b) 37 °C.


(PNVCL-co-PNVP)6

(PNVCL)6

((PNVCL-co-PNVP)-b-PVAc)6

(PNVCL-b-PVAc)6

Preparation of a Mini-Library of Thermo-Responsive Star(NVCL/NVP-VAc) Polymers with Tailored Properties Using aHexafunctional Xanthate RAFT Agent

Norma A. Cortez Lemus and A. Licea-Claverie, Polymers , 2018, 10 (1), 20


(PNVCL-co-PNVP)6(PNVCL)6((PNVCL-co-PNVP)-b-PVAc)6

(PNVCL-b-PVAc)6

Norma A. Cortez Lemus and A. Licea-Claverie, Polymers, 2018, 10 (1), 20

Scheme 1. Synthesis of hexafunctional star polymers and block copolymers based onPNVCL using a multifunctional xanthate as a RAFT agent.

Figure 2. Dynamic light scattering (DLS) measurements (c = 1 mg/mL in water): (a) effects ofmolecular weight on the lower critical solution temperature (LCST) of star (PNVCL)6 polymers;and (b) evolution of the Dh of the (PNVCL)6 polymers as a function of the temperature.


Star (PNVCL)6 polymers in aqueous solution: LCST and Dh

Figure 3. DLS measurements. Evolution of the Dh of the star (PNVCL)6 polymers as a function of the molecular weight (c = 1 mg/mL).

Figure 5. 1H-NMR (400 MHz) spectrum of a star (PNVCL-b-PVAc)6 copolymer in CDCl3(Table 2, sample (PNVCL99-b-PVAc21)6, Mn GPC = 94,300 g/mol, Ð = 1.04, 20% of PVAc).


Star (PNVCL-b-PVAc)6

Figure 6. DLS measurements (c = 1 mg/mL in water) for star (PNVCL-b-PVAc)6 block copolymers:(a) Dh of (PNVCL99)6 and the corresponding (PNVCL99-b-PVAc)6 block copolymers, measured at 20°C; and (b) evolution of the Dh of the (PNVCL99)6 and (PNVCL99-b-PVAc)6 as a function of thetemperature.

Star (PNVCL-b-PVAc)6


Figure 7. Self-assembly in aqueous solution of star (PNVCL-b-PVAc)6 block copolymers: (a) multiple star micelles; and (b) single flower-like micelle.

Norma A. Cortez Lemus and A. Licea-Claverie, Polymers . 2018, 10 (1), 20

Scheme 3. Synthesis of the star [PVAc-b-(PNVCL-co-PNVP)]6

block copolymers.


Figure 8. 1H NMR spectrum (400 MHz) in CDCl3 of star-shaped (PVAc-b-(PNVCL-co-PNVP))6

block copolymers. Sample (PVAc30-b-(PNVCL28-co-PNVP17))6, Mn GPC = 42,290 g/mol, Ð = 1.1 (Table 4, Entry 2).


Figure 9. “Height” image and “3D reconstruction“ from AFM of almost spherical aggregates obtained from six-arm star block copolymers on a mica substrate (c = 0.02 mg/mL): (a,b) Sample (PVAc22-b-PNVCL11)6, Entry 1, Table 4; (c,d) Sample [PVAc30-b-(PNVCL28-co-PNVP17)]6, Entry 2, Table 4; and (e,f) Sample [PVAc17-b-(PNVCL10-co-PNVP7)]6, Entry 3, Table 4.

AFM of almost spherical aggregates from star [PVAc-b-(PNVCL-co-PNVP)]6 block copolymers.

1730 MTX

Sample (PVAc22-b-PNVCL11)6 loaded with MTX

17108C

RMS: 1.16DP = 140 nm

Sample [PVAc30-b-(PNVCL28-co-PNVP17)]6 loaded with MTX

Star [PVAc-b-(PNVCL-co-PNVP)]6 block copolymers.

1766

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Star-shaped poly(N-vinylcaprolactam) and copolymerscgiqtectijuana.mx/wp-content/uploads/2019/02/STAR-PNVCL-POLYMER… · Star-shaped poly(N-vinylcaprolactam) and copolymers High density