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Page 1: R. A. Miranda, F. Medina, J.E. Sueiras and A.M. Segarra*etseq.urv.cat/doctorat/fotos/posters1/Alex Miranda.pdf · Nanohybrid materials as catalysts of asymmetric reactions with potential

Nanohybrid materials as catalysts of asymmetric reactions with potential pharmaceutical applications

Nanohybrid materials as catalysts of asymmetric reactions with potential pharmaceutical applications

R. A. Miranda, F. Medina, J.E. Sueiras and A.M. Segarra*R. A. Miranda, F. Medina, J.E. Sueiras and A.M. Segarra*

Departament d’Enginyeria Química, Universitat Rovira i Virgili, Tarragona, Av. Països Catalans, 26, 43007, SpainResearch Center on Engineering of Materials and Micro/nano Sistems, Universitat Rovira i Virgili, Tarragona, MarcelResearch Center on Engineering of Materials and Micro/nano Sistems, Universitat Rovira i Virgili, Tarragona, Marcel

*E-mail: [email protected]

AntecedentsRecently, nanohybrid materials received considerable interest due to their wide

number of applications in nanoscience and catalysis. They often exhibit

extraordinary high synergetic and complementary behaviour between two

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Antecedents

extraordinary high synergetic and complementary behaviour between two

component materials. In particular, the combination of hydrotalcite-like materials

(HTs) and chiral molecules such as aminoacids (AA) and poly-aminoacids (PAA)

offer new areas for developing hybrids with the desired functionality [1], as well as

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offer new areas for developing hybrids with the desired functionality [1], as well as

these materials are able to catalyze the synthesis of chiral drugs [2]. Some

examples of organic-inorganic nanohybrid materials based on AA and HTs used as

catalysts have been reported. However, in all cases the synthesis time of the

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catalysts have been reported. However, in all cases the synthesis time of the

material is higher than 24 hours. And, to the best of our knowledge, there is any in-

depth study of the interaction between the AA or PAA and HTs [3].

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Results and Discussion

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Results and Discussion

Synthesis and characterization of nanohybrid materials

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Synthesis and characterization of nanohybrid materials

Chiral molecules Method A30 min. at r.t.magnetic stirring

L-Leu/HTA0.44

(AA)

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magnetic stirringL-Pro/HTA0.44

L-Leu/HTB1.09

Method B180 min. at 353 Kmagnetic stirring

L-Leu

L-Pro

or

(AA)

COOH

NH2

OH

O

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L-Leu/HTB1.09

L-Pro/HTB1.02

magnetic stirringL-Pro

30 min. at r.t.magnetic stirring PLLc/HT

(PAA)

NH

COOH

O O

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[Mg2Al(OH)7]·mH2O

magnetic stirring PLLc/HT(0.08 mg PLLc/mg HT)

PLLs/HT(0.30 mg PLLs/mg HT)

PLLc

PLLs

orH

HN

OH

O

n

H2NNH

O HN

O

HN

O

NH

O

NH2

n m

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Fig.1. Methods of immobilization of AA and PAA onto rehydrated HT. AA amount was calculated using TOC analysis. PAA

amount was calculated using TGA.

PLLs

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HRTEM

7.7 Å7.7 ÅL-Leu/HTA PLLc/HT

XRD

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����

♦♦♦♦

♦♦♦♦

HT

♦♦♦♦

19.3 Å

7.7 Å

19.3 Å

7.7 ÅL-Leu/HTA0.44 PLLc/HT

Gru

p d

Gru

p d´́investigació

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���� ��������

HT

L-Leu/HTA0.44

����

����

����

14.7 Å L-Pro/HTA0.44

L-Pro/HTB1.02

����

14.7 Å

L-Leu/HTB

Gru

p d

Gru

p d

��������

L-Leu/HTB1.0911.6 Å

����

����PLLc/HT0.08mg

PLLs/HT0.30mg

11.6 Å

L-Leu/HTB1.09 PLLs/HT

Gru

p d

Gru

p d

2-θ

4 10 20 30 40 50 60 70

♦ Basal peaks of (003) and (006) of HT.

� Basal peaks of planes (003), (006) and (009) of the HT with chiral molecule intercalated.� Basal peak of L-Leu.

PLLs/HT0.30mg

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––

MAS-NMR and FT-IR

Fig. 2. HRTEM and XRD analysis of the synthesized nanohybrid material.

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MAS-NMR and FT-IR

O(H)H

α

β

γ

δH2N Cα Cβ Cγ

CδH3H

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Material

13C MAS-NMR

(ppm)

FT-IR

(cm-1)

NH

O

αγ

H2N Cα Cβ

H2

H CδH3

COO(H)

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Material (ppm) (cm-1)COO(H) Cα Cβ Cγ Cδ

νasCOO(H)

L-Leu 176 55 44 27 24 1581

L-Leu/HTA 185 58 47 27 24 1560

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L-Leu/HTA0.44 185 58 47 27 24 1560

L-Leu/HTB1.09 185 59 46 26 16 1560

L-Pro 178 65 49 36 28 1624

L-Pro/HTA 185 67 50 34 28 1624 + 1570

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Table 1. 13C MAS-NMR and FT-IR frequencies of asymmetric vibrations of carboxylic group of free and immobilized AA .

L-Pro/HTA0.44 185 67 50 34 28 1624 + 1570

L-Pro/HTB1.02 185 66 50 35 28 1570

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Nature of the biohybrid materials

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L-leu/HT-A

L-Leu/HTA L-Leu/HTB PLL/HT

Acknowledgements: We thank MCI from Spain and URV for the economical support, Dr. J. Llorca(Universitat Politècnica de Catalunya) for performing the HRTEM experiments, and Drs. G. Ramisand E. Finocchio (Genoa University) for helpful discussions about the FTIR experiments. R.-A.M.thanks to URV for his predoctoral fellowship. F. Medina thanks to Gencat for the ICREA ACADEMIAthanks to URV for his predoctoral fellowship. F. Medina thanks to Gencat for the ICREA ACADEMIAaward.References: [1] U. Costantino, V. Ambrogi, M. Nocchetti, L. Perioli. Micropor. Mesopor. Mater. 107,149 (2008). [2] C.Lauret, and S. Roberts. AldrichimicaActa. 35, 47 (2002) and references there in. [3]B.M. Chaudary, B. Kavita, N. Sreenivasa Chowdary, B. Sreedhar, M. Lakshmi Katam. J. Catal. letter,B.M. Chaudary, B. Kavita, N. Sreenivasa Chowdary, B. Sreedhar, M. Lakshmi Katam. J. Catal. letter,78, 373 (2001); S. Vijaikumar, A. Dhakshinamoorthy, K. Pitchumani, Applied Catalysis A: General340, 25 (2008).

materials as catalysts of asymmetric reactions with potential pharmaceutical applications

materials as catalysts of asymmetric reactions with potential pharmaceutical applications

R. A. Miranda, F. Medina, J.E. Sueiras and A.M. Segarra*R. A. Miranda, F. Medina, J.E. Sueiras and A.M. Segarra*

Departament d’Enginyeria Química, Universitat Rovira i Virgili, Tarragona, Av. Països Catalans, 26, 43007, SpainResearch Center on Engineering of Materials and Micro/nano Sistems, Universitat Rovira i Virgili, Tarragona, Marcel-li Domingo, s/n, 43007, Spain Research Center on Engineering of Materials and Micro/nano Sistems, Universitat Rovira i Virgili, Tarragona, Marcel-li Domingo, s/n, 43007, Spain

mail: [email protected]

Our projectThe aim of this work is the design of different novel biohybrid nanomaterials based

on L-Leucine (L-Leu), L-Proline (L-Pro) and Poly-L-Leucine (PAA) immobilized onto

HTs. These materials have been used as catalysts for the Aldol asymmetric reactions

Our project

HTs. These materials have been used as catalysts for the Aldol asymmetric reactions

and the asymmetric epoxidation of α,β-unsaturated ketones. Some of the obtained

products are precursors of Naproxen (anti-inflammatory), Taxol (cancer

chemotherapy), Stantin (lower cholesterol levels), or (+)-fenoprofen (rheumatoidchemotherapy), Stantin (lower cholesterol levels), or (+)-fenoprofen (rheumatoid

arthritis). The nature of the resulting biohybrid materials and the interactions between

their components were characterized by TOC, XRD, HRTEM, FT-IR, 13C and 13Al

NMR-MAS, MALDI and ESI-TOF mass spectroscopy.

Results and Discussion

NMR-MAS, MALDI and ESI-TOF mass spectroscopy.

Results and Discussion

Study of asymmetric reactions

Asymmetric epoxidation reaction of chalcone

Study of asymmetric reactions

O O O O O

Ph

O

Ph Ph

O

Ph

O

Ph

O

Ph

O

Ph

O

Ph

O

Ph

O

Ph

OCatalyst

NaOH, H2O2, TBABTHF, 1.5h, rt

+ + +

(R,R)-cisChalcone (R,S)-trans (S,R)-trans (S,S)-cis (R,R)-cis

(R,R) (S,S)

L-Leu1

L-Leu/HTB1.091

CatalystHT1

L-Leu/HTA0.441

PLLc/HT2

PLLc2

PLLs/HT2

PLLs2

1Reaction conditions: 1.44 mmol chalcone, 1.5 equiv. NaOH 2M, 1.5 equiv. H2O2 (30% wt), 0.042 mmol TBAB, 3 mL Hexane, catalyst with an L-Leu

content of 18 mg, 3h, rt. The ee was determined by chiral HPLC analysis (Chiralpak IA). The conversion was determined by 1H NMR (Varian

400MHZ).400MHZ).2Reaction conditions: 0.24 mmol chalcone, 10 equiv. NaOH 5M, 11.9 equiv. H2O2 (30% wt), 0.024 mmol TBAB, 1 mL Toluene, 200%w PLL, 1h, rt.

The ee was determined by chiral HPLC analysis and the conversion was determined by 1H NMR.

Direct asymmetric aldol reaction

NO

H

O

O

THF, rt

O OH

+Catalyst

O OH

+

NO2 NO2 NO2(R)-Enantiomer (S)-Enantiomer

(R,R) (S,S)

HTCatalyst

L-Pro/HTA0.44

R

HT

L-Leu/HTB1.02

CatalystL-Pro

L-Pro/HTA0.44

S

Reaction conditions: 0.1 mmol L-Pro, 13.6 mmol acetone, 0.5 mmol aldehyde, 2 mL THF, 24h, rt. The ee was determined by chiral HPLC analysis

(Chiralpak IA). The conversion was determined by 1H NMR (Varian 400MHZ).(Chiralpak IA). The conversion was determined by 1H NMR (Varian 400MHZ).

Conclusions

Two different biohybrid materials based on AA into a hydrotalcite rehydrated under ultrasounds weresynthesized using efficient and easy protocols. Method A: AA immobilized by replacing hydroxyl ions atthe edges of HT. Method B: AA immobilized by intercalation.

Conclusions

the edges of HT. Method B: AA immobilized by intercalation.

The AA immobilized in the interlayer spacing of HT (method B), presented enantioselectivity in the aldol and J-C epoxidation reactions.

The L-Pro/HTB nanohybrid achieved different catalytic behavior for the direct aldol reaction than pure L-

The L-Leu/HTA presented high activity towards the trans-epoxide.

The L-Pro/HTB nanohybrid achieved different catalytic behavior for the direct aldol reaction than pure L-Pro, showing moderate conversions with inversion of the enantioselectivity.

The PLLs/HT presented similar activity and selectivity than the PLLc/HT. The PLLs/HT was recycled and reused during 5 consecutive runs (Results not showed). reused during 5 consecutive runs (Results not showed).

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