Post-doc Category: Engineering and Technology Degree Level: PhD ...
Post-doc Category: Engineering and Technology Degree Level: PhD Abstract ID#1221
Post Doctoral Associate Kartik Temburnikar Mentor: Hicham Fenniri
Rosette Nanotubes: Investigating New Frontiers in Material Design Abstract. Surface functionalization of Rosette Nanotubes (RNTs) afford them varied properties that have found use in tissue engineering and drug delivery. The nanoscale self-assembly and surface functionalization afford remarkable opportunities in evolution of novel materials. Using chemical tools we intend to harness emergent properties of RNTs to develop novel materials and applications. What are Rosette Nanotubes? Our lab has synthesized heterocyclic compounds that combines the Watson-Crick base pairing motifs of Guanosine and Cytosine into one single compound, G^C base. This molecule base pairs with itself to form a hexamer consisting of 18 hydrogen bonds. The hydrophobic nature of the G^C bases drives the stacking of hexamers leading to a supramolecule with a hollow tube along the length of the stack. The non hydrogen-bonding face of the G^C base presents itself for functionalization that has resulted in several peripherally decorated nanotubes. b
a
Rosette Nanotubes in DNA Nanotechnology. DNA double helix is the most prevalent architecture in DNA nanotechnology and has been used to assemble 3WJ, 4WJ and 5WJ. Other DNA architectures like triplex and quadruplex assemble under specific conditions and are useful in stimuli responsive nanodevices. We intend to couple the G^C base to nucleic acid backbone that will help expand the realm of nucleic acid architecture and applications. a
b
c
N N N
O H H
H
N
N
G N H H
H
N H
N
N
N C N O
NH2
H N N G O
c
H3N
O
-
O
C+ N H
H
N H
N
N
Figure 1. a. Chemical structure of G^C base coupled to Lysine (K1), b. Hexamric rosette, c. Rosette Nanotube.
G
N
N
N H
N
O H
N
H N
H N GC
N
Synthesis of G^C base. O
Cl a
HN O
N H
O
OBn CHO
N Cl
b
Cl
N
BocN
OBn NH2 d
N BocN
N
c
e O
N
NH
BocN
O
BocN
f
N N
O
N
H N
N
H
N
O H
N
H
H
N
N
f
N
N
N H
H O
H
H O
N
N
O
GC N H
N H
NH2
O
O-
N N H
N GC
+
H3N
N
H N
O
+
O
H H
N X-
H
O
N
GC
N H
N
N
Figure 4. a. Chemical structure of xK1, b. Hexamric rosette, c. Rosette Nanotube.
O N
N
1.4 nm
N
4.3 nm g
a
b
HN
Figure 2. a. DNA duplex (X-ray, PDB 1BNA), b. C+-G-C triplex (NMR, PDB 1BWG), c. G-quadruplex (NMR, PDB 139D), d. GC sextuplet, e. DNA three-arm junction, f. DNA four-arm junction, g. DNA five-arm junction.
NH2
HN
N N X-
O +
H3N
N
O +
NH2
O
Oa. POCl3, DMF, reflux, 68%, b. i. allylamine, CH2Cl2, -78 oC, 82%, ii. CH3NH2, THF, 0 oC, 80%, iii. BnOH, NaH, THF, reflux, 95%, iv. Boc2O, TEA, DMAP, THF, rt, 62%, c. i. NH2NH2.HCl, Pyridine, 60 oC, 97%, ii. TFA, TEA, THF, 0 oC, 88%, d. Cl3CONCO, CH2Cl2, 0 oC, 90%, e. i. Boc2O, TEA, DMAP, THF, 62%, ii. OsO4 in t-BuOH, 50% NMO in H2O, THF, rt for 6 h, then NIO4 in H2O, 63%, f. i. Protected L-Lysine, DIPEA, 1,2-DCE, rt, 10 min then Na(OAc)3BH, rt, 48 h, 82%, ii. TFA/thianisole, rt, 96 h, 87%.
Rosette Nanotubes in XNA Nanotechnology. Xeno-nucleic acids (XNA) constitute chemicaly modified scaffolds, and have shown to endow enhanced biophysical properties like higher specificity, flexibility and in-vivo stability over DNA and RNA. We intend to study peptide (PNA) and propylene glycol (GNA) backbones to G^C base in addition to 2ˈ-deoxy ribose (DNA) backbones to expand the field of XNA nanotechnology. OR
NH2
N
H2N
N O H R = Protecting group
Drug Delivery
N
N
O NH
N O
DMTO
N
N
N
N
O
Photovoltaics N
O P
N
N
O
Boc2N
N N
N
N
N O
CN
DNA
P N
O
BocHN
N
N
HN
N N
N
N
OH
PNA
References. 1. Ann Rev Biochem, 79, 65, 2010, 2. Science, 347, 1260901, 2015, 3. Angew Chem Int Ed, 50, 3124, 2011, 4. Acc Chem Res, 47, 1836, 2014, 5. Ann Rev Biochem, 73, 791, 2004, 6. Chem Biol, 19, 937, 2012, 7. Chem Biol, 19, 1360, 2012, 8. Biochem, 30, 5667, 1991, 9. Angew Chem Int Ed, 48, 4134, 2009, 10. J Theor Biol, 99, 237, 1982, 11. Acc Chem Res, 43, 1092, 2010, 12. Acc Chem Res, 32, 624, 1999, 13. Trends Biotechnol, 32, 321, 2014.
Electron Donor
+
NH2
+
H3N
Energy Transfer
O
N X-
O
b
NH2
NHBoc
Figure 3. Structures of DNA, GNA and PMA monomers. References. 1. J Am Chem Soc, 123, 3854, 2001, 2. Proc Natl Acad Sci USA, 99, 6487, 2002, J Am Chem Soc, 124, 11064, 2002, 3. Biomaterials, 30, 1309, 2009, 4. Int J Nanomed, 47, 1034, 2011, 5. J Am Chem Soc, 132, 15136, 2010, 6. Biomaterials, 30, 3084, 2009, 7. Mater Res Soc Symp Proc, 2014.
O HN
N N
O
CN
GNA
OR
N
DMTO O
O
a
OR
N
Figure 5. a. UV-vis spectra for xK1, b. Fluorescence spectra for xK1-RNT (λexc = 388 nm, ca. 2x10-5 M in water)
Rosette Nanotubes in Molecular Electronics. Encouraged by fluorescent properties of xRNT, we intend to explore photoelectric properties of tetracyclic G^C base that consists of two pyridine expansion. Furthermore, conjugation of RNTs with suitable molecular entities should help harness the photoinduced electro-magnetic energy from RNTs.
N
N
Applications of Rosette Nanotubes
Nanomedicine
O H
H
N GC
N
NH
N
,
Tissue Engineering
O
HN
N
H
NH2
CN
N
OBn NBoc2
N N
N
N
c
OBn CHO
N
O HN
N
H
O
e
H
N H
N
N
O
N H
N
1.0 nm
N
b
G N
N
G
N H
N
N C N
H
GC
O
N
H
N
H H N
O
3.4 nm
H
d N
O
H
a
N
O H
N
+
O M+
+
X-
N
H
H H N
N
O
N
H
O
N N
N
H N
O
N G
N
H
H N
Photophysics of Exapanded Rosette Nanotubes. Introdution of a pyridine ring in the G^C base has been shown to impart photophysical properties to Rosette Nanotubes and enable formation of J-type aggregates. The photophyscial properties and hierarchical self-assembly are important features for applications in opto-electronics and light harvesting. Functionalization of the non hydrogen-bonding face of the G^C base affords opportunities to tune the structure and function of the supramolecule.
Bridge
Electron Acceptor
O
O-
Figure 6. a. Structures of xxK1, b. Schematics of molecular electronics.
References. 1. J Am Chem Soc, 132, 15136, 2010, 2. J Am Chem Soc, 75, 7233, 2010, 3. Nat Rev Mat, 1, 1, 2016.
Post Doctoral Associate Kartik Temburnikar Mentor: Hicham Fenniri
Rosette Nanotubes: Investigating New Frontiers in Material Design Abstract. Surface functionalization of Rosette Nanotubes (RNTs) afford them varied properties that have found use in tissue engineering and drug delivery. The nanoscale self-assembly and surface functionalization afford remarkable opportunities in evolution of novel materials. Using chemical tools we intend to harness emergent properties of RNTs to develop novel materials and applications. What are Rosette Nanotubes? Our lab has synthesized heterocyclic compounds that combines the Watson-Crick base pairing motifs of Guanosine and Cytosine into one single compound, G^C base. This molecule base pairs with itself to form a hexamer consisting of 18 hydrogen bonds. The hydrophobic nature of the G^C bases drives the stacking of hexamers leading to a supramolecule with a hollow tube along the length of the stack. The non hydrogen-bonding face of the G^C base presents itself for functionalization that has resulted in several peripherally decorated nanotubes. b
a
Rosette Nanotubes in DNA Nanotechnology. DNA double helix is the most prevalent architecture in DNA nanotechnology and has been used to assemble 3WJ, 4WJ and 5WJ. Other DNA architectures like triplex and quadruplex assemble under specific conditions and are useful in stimuli responsive nanodevices. We intend to couple the G^C base to nucleic acid backbone that will help expand the realm of nucleic acid architecture and applications. a
b
c
N N N
O H H
H
N
N
G N H H
H
N H
N
N
N C N O
NH2
H N N G O
c
H3N
O
-
O
C+ N H
H
N H
N
N
Figure 1. a. Chemical structure of G^C base coupled to Lysine (K1), b. Hexamric rosette, c. Rosette Nanotube.
G
N
N
N H
N
O H
N
H N
H N GC
N
Synthesis of G^C base. O
Cl a
HN O
N H
O
OBn CHO
N Cl
b
Cl
N
BocN
OBn NH2 d
N BocN
N
c
e O
N
NH
BocN
O
BocN
f
N N
O
N
H N
N
H
N
O H
N
H
H
N
N
f
N
N
N H
H O
H
H O
N
N
O
GC N H
N H
NH2
O
O-
N N H
N GC
+
H3N
N
H N
O
+
O
H H
N X-
H
O
N
GC
N H
N
N
Figure 4. a. Chemical structure of xK1, b. Hexamric rosette, c. Rosette Nanotube.
O N
N
1.4 nm
N
4.3 nm g
a
b
HN
Figure 2. a. DNA duplex (X-ray, PDB 1BNA), b. C+-G-C triplex (NMR, PDB 1BWG), c. G-quadruplex (NMR, PDB 139D), d. GC sextuplet, e. DNA three-arm junction, f. DNA four-arm junction, g. DNA five-arm junction.
NH2
HN
N N X-
O +
H3N
N
O +
NH2
O
Oa. POCl3, DMF, reflux, 68%, b. i. allylamine, CH2Cl2, -78 oC, 82%, ii. CH3NH2, THF, 0 oC, 80%, iii. BnOH, NaH, THF, reflux, 95%, iv. Boc2O, TEA, DMAP, THF, rt, 62%, c. i. NH2NH2.HCl, Pyridine, 60 oC, 97%, ii. TFA, TEA, THF, 0 oC, 88%, d. Cl3CONCO, CH2Cl2, 0 oC, 90%, e. i. Boc2O, TEA, DMAP, THF, 62%, ii. OsO4 in t-BuOH, 50% NMO in H2O, THF, rt for 6 h, then NIO4 in H2O, 63%, f. i. Protected L-Lysine, DIPEA, 1,2-DCE, rt, 10 min then Na(OAc)3BH, rt, 48 h, 82%, ii. TFA/thianisole, rt, 96 h, 87%.
Rosette Nanotubes in XNA Nanotechnology. Xeno-nucleic acids (XNA) constitute chemicaly modified scaffolds, and have shown to endow enhanced biophysical properties like higher specificity, flexibility and in-vivo stability over DNA and RNA. We intend to study peptide (PNA) and propylene glycol (GNA) backbones to G^C base in addition to 2ˈ-deoxy ribose (DNA) backbones to expand the field of XNA nanotechnology. OR
NH2
N
H2N
N O H R = Protecting group
Drug Delivery
N
N
O NH
N O
DMTO
N
N
N
N
O
Photovoltaics N
O P
N
N
O
Boc2N
N N
N
N
N O
CN
DNA
P N
O
BocHN
N
N
HN
N N
N
N
OH
PNA
References. 1. Ann Rev Biochem, 79, 65, 2010, 2. Science, 347, 1260901, 2015, 3. Angew Chem Int Ed, 50, 3124, 2011, 4. Acc Chem Res, 47, 1836, 2014, 5. Ann Rev Biochem, 73, 791, 2004, 6. Chem Biol, 19, 937, 2012, 7. Chem Biol, 19, 1360, 2012, 8. Biochem, 30, 5667, 1991, 9. Angew Chem Int Ed, 48, 4134, 2009, 10. J Theor Biol, 99, 237, 1982, 11. Acc Chem Res, 43, 1092, 2010, 12. Acc Chem Res, 32, 624, 1999, 13. Trends Biotechnol, 32, 321, 2014.
Electron Donor
+
NH2
+
H3N
Energy Transfer
O
N X-
O
b
NH2
NHBoc
Figure 3. Structures of DNA, GNA and PMA monomers. References. 1. J Am Chem Soc, 123, 3854, 2001, 2. Proc Natl Acad Sci USA, 99, 6487, 2002, J Am Chem Soc, 124, 11064, 2002, 3. Biomaterials, 30, 1309, 2009, 4. Int J Nanomed, 47, 1034, 2011, 5. J Am Chem Soc, 132, 15136, 2010, 6. Biomaterials, 30, 3084, 2009, 7. Mater Res Soc Symp Proc, 2014.
O HN
N N
O
CN
GNA
OR
N
DMTO O
O
a
OR
N
Figure 5. a. UV-vis spectra for xK1, b. Fluorescence spectra for xK1-RNT (λexc = 388 nm, ca. 2x10-5 M in water)
Rosette Nanotubes in Molecular Electronics. Encouraged by fluorescent properties of xRNT, we intend to explore photoelectric properties of tetracyclic G^C base that consists of two pyridine expansion. Furthermore, conjugation of RNTs with suitable molecular entities should help harness the photoinduced electro-magnetic energy from RNTs.
N
N
Applications of Rosette Nanotubes
Nanomedicine
O H
H
N GC
N
NH
N
,
Tissue Engineering
O
HN
N
H
NH2
CN
N
OBn NBoc2
N N
N
N
c
OBn CHO
N
O HN
N
H
O
e
H
N H
N
N
O
N H
N
1.0 nm
N
b
G N
N
G
N H
N
N C N
H
GC
O
N
H
N
H H N
O
3.4 nm
H
d N
O
H
a
N
O H
N
+
O M+
+
X-
N
H
H H N
N
O
N
H
O
N N
N
H N
O
N G
N
H
H N
Photophysics of Exapanded Rosette Nanotubes. Introdution of a pyridine ring in the G^C base has been shown to impart photophysical properties to Rosette Nanotubes and enable formation of J-type aggregates. The photophyscial properties and hierarchical self-assembly are important features for applications in opto-electronics and light harvesting. Functionalization of the non hydrogen-bonding face of the G^C base affords opportunities to tune the structure and function of the supramolecule.
Bridge
Electron Acceptor
O
O-
Figure 6. a. Structures of xxK1, b. Schematics of molecular electronics.
References. 1. J Am Chem Soc, 132, 15136, 2010, 2. J Am Chem Soc, 75, 7233, 2010, 3. Nat Rev Mat, 1, 1, 2016.
