PMID- 16212369
OWN - NLM
STAT- MEDLINE
DCOM- 20060710
LR  - 20161019
IS  - 0020-1669 (Print)
IS  - 0020-1669 (Linking)
VI  - 44
IP  - 21
DP  - 2005 Oct 17
TI  - Structural and spectroscopic study of reactions between chelating zinc-binding 
      groups and mimics of the matrix metalloproteinase and disintegrin metalloprotease 
      catalytic sites: the coordination chemistry of metalloprotease inhibition.
PG  - 7431-42
AB  - To understand the coordination chemistry of zinc-binding groups (ZBGs) with 
      catalytic zinc centers in matrix metalloproteinases (MMPs) and disintegrin 
      metalloproteases (ADAMs), we have undertaken a model compound study centered 
      around tris(3,5-methylphenypyrazolyl)hydroboratozinc(II) hydroxide and aqua 
      complexes ([Tp(Ph,Me)ZnOH] and [Tp(Ph,Me)Zn(OH2)]+, respectively, wherein 
      (Tp(Ph,Me))- = hydrotris(3,5-methylphenylpyrazolyl)borate) and the products of 
      their reactions with a class of chelating Schiff's base ligands. The results show 
      that the protic ligands, HL (HL = N-propyl-1-(5-methyl-2-imidazolyl)methanimine 
      (5-Me-4-ImHPr), N-propyl-1-(4-imidazolyl)methanimine (4-ImHPr), and 
      N-propyl-1-(2-imidazolyl)methanimine (2-ImHPr)), react with [Tp(Ph,Me)ZnOH] and 
      give products with the general formula [Tp(Ph,Me)ZnL], whereas reactions with 
      neutral aprotic ligands, L' (L' = N-propyl-1-(1-methyl-2-imidazolyl)methanimine 
      (1-Me-2-ImPr) and N-propyl-1-(2-thiazolyl)methanimine (2-TaPr)), yield the 
      corresponding [Tp(Ph,Me)ZnL]+ complexes. Although the phenol group of 
      N-propyl-1-(2-hydroxyphenyl)methanimine (2-HOPhPr) is protic, this ligand forms a 
      cationic four-coordinate complex containing an intraligand hydrogen bond. The 
      solid-state structures of these complexes were determined by single-crystal X-ray 
      diffraction, and the results showed that the protic ligands form five-membered 
      chelates of the Zn2+ ion. All ligands displace the aqua ligand in 
      [Tp(Ph,Me)Zn(OH2)]+ to yield complexes having 1H NMR spectra consistent with the 
      formation of five membered chelates. The 1H resonance frequencies of the 
      chelating ligands typically shift upfield upon coordination to the zinc center, 
      due to ring current effects from the pendant phenyl groups of the (Tp(Ph,Me))- 
      ligand. Thus, the 1H NMR spectra provide a convenient and sensitive means of 
      tracking the solution reactions by titration. The resulting series of spectra 
      showed that the stabilities of the chelates in solution depend on the propensity 
      of the ligands to deprotonate upon chelation of the zinc center. The behaviors of 
      these bidentate ZBGs provide insight into the structural and electronic factors 
      that contribute to the stabilities of inhibited MMPs and ADAMs and suggest that 
      the proton acidity of the coordinated ZBG may be a crucial criterion for 
      inhibitor design.
FAU - He, Hongshan
AU  - He H
AD  - Department of Chemistry, Biochemistry, and Molecular Biology, North Dakota State 
      University, Fargo, North Dakota 58105-5516, USA.
FAU - Puerta, David T
AU  - Puerta DT
FAU - Cohen, Seth M
AU  - Cohen SM
FAU - Rodgers, Kenton R
AU  - Rodgers KR
LA  - eng
GR  - P20 RR015566/RR/NCRR NIH HHS/United States
GR  - P20RR15566/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Inorg Chem
JT  - Inorganic chemistry
JID - 0366543
RN  - 0 (Ligands)
RN  - 0 (Schiff Bases)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - ADAM Proteins/chemistry/*metabolism
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Conserved Sequence
MH  - Ligands
MH  - Matrix Metalloproteinases/chemistry/*metabolism
MH  - Models, Molecular
MH  - Schiff Bases
MH  - Zinc/chemistry/*metabolism
EDAT- 2005/10/11 09:00
MHDA- 2006/07/13 09:00
CRDT- 2005/10/11 09:00
PHST- 2005/10/11 09:00 [pubmed]
PHST- 2006/07/13 09:00 [medline]
PHST- 2005/10/11 09:00 [entrez]
AID - 10.1021/ic050723p [doi]
PST - ppublish
SO  - Inorg Chem. 2005 Oct 17;44(21):7431-42. doi: 10.1021/ic050723p.