Enantiomeric pair of copper(II) polypyridyl-alanine complexes: Effect of chirality on their interaction with biomolecules.
Like chiral organic drugs, the chemical and biological properties of metal complexes can be dependent on chirality. Two pairs of [Cu(phen)(ala)(H2O)]X·xH2O (phen=1.10-phenanthroline: X=NO3(-); ala: l-alanine (l-ala), 1 and d-alanine (d-ala) 2; and (X=Cl(-); ala: l-ala, 3 and d-ala, 4) complex salts (x=number of lattice water molecules) have been synthesized and characterized. The crystal structure of 3 has been determined. The same pair of enantiomeric species, viz. [Cu(phen)(l-ala)(H2O)](+) and [Cu(phen)(d-ala)(H2O)](+), have been identified to be present in the aqueous solutions of both 1 and 3, and in those of both 2 and 4 respectively. Both 3 and 4 bind more strongly to ds(AT)6 than ds(CG)6. There is no or insignificant effect of the chirality of 3 and 4 on the production of hydroxyl radicals, binding to deoxyribonucleic acid from calf thymus (CT-DNA), ds(CG)6, G-quadruplex and 17-base pair duplex, and inhibition of both topoisomerase I and proteasome. Among the three proteasome proteolytic sites, the trypsin-like site is inhibited most strongly by these complexes. However, the chirality of 3 and 4 does affect the number of restriction enzymes inhibited, and their binding constants towards ds(AT)6 and serum albumin.
Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. Electronic address: NgChewHee@imu.edu.my.
Chew Hee
CH
Ng
Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia; Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: estichan91@gmail.com.
Cheang Wei
CW
Chan
Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. Electronic address: janice_ljw_92@yahoo.com.
Jing Wei
JW
Lai
Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. Electronic address: inghong_ooi@imu.edu.my.
Ing Hong
IH
Ooi
Faculty of Science, Universiti Tunku Abdul Rahman, 31900 Kampar, Perak, Malaysia. Electronic address: Destiny.chong.james@gmail.com.
Kok Vei
KV
Chong
Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: mjamil@um.edu.my.
Mohd Jamil
MJ
Maah
Department of Biological Sciences, Sunway University, 47500 Bandar Sunway, Malaysia. Electronic address: hoilings@sunway.edu.my.
Hoi Ling
HL
Seng
D000409:Alanine / Q000737:chemistry*; D000818:Animals; D002413:Cations, Divalent; D002417:Cattle; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry; D006801:Humans; D017665:Hydroxyl Radical / Q000737:chemistry; D010618:Phenanthrolines / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry*; D059748:Proteolysis; D011725:Pyridines / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry; D013237:Stereoisomerism; D059004:Topoisomerase I Inhibitors / Q000737:chemistry
D002413:Cations, Divalent; D056831:Coordination Complexes; D010618:Phenanthrolines; D011725:Pyridines; D012709:Serum Albumin; D059004:Topoisomerase I Inhibitors; D017665:Hydroxyl Radical; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; D046988:Proteasome Endopeptidase Complex; D004264:DNA Topoisomerases, Type I; D000409:Alanine; C025205:1,10-phenanthroline
Chirality; Deoxyribonucleic acid; Proteasome; Restriction enzyme; Ternary copper(II) complexes; Topoisomerase I