M. Ci, #0.11#mmol)#was#dissolved#in#dry#acetone#(10#mL).#Ag 2 O#(154#mg,#0.66#mmol)#was#added# and# the# mixture# was# stirred# for# 2# h# at# room# temperature.# The# red# solution# of# quinone# methide# formed#was#separated#from#the#solid#by#centrifugation#(rt,#400#g,#5#min)#and#evaporated.#A#red#oil# (63# mg, C 26 H 22 O 2 Os+H] + )#calcd:#559.1308 90%# yield)# of# quinone# methide# was# obtained.# 1# mL# of# acetone# was# added# to# dissolve# the# quinone# methide.# Pentane# was# added# to# precipitate# the# quinone# methide# (red# solid).# 1 H# NMR# ?, pp.559-1292

#. #. Mathias, #. #. #welch, and #. #katzenellenbogen, (Conclusion( In!this!work,!two!classes!of!organometallic!compounds!of!osmium,!i.e.,!the!triosmium!carbonyl! clusters!and!the!hydroxyosmocifens, #33,#3143.# ! 100! Chapter, 1990.

!. The, ! the! triosmium! carbonyl! clusters!exert!their!activity!by!virtue!of!the!metal!centre,!while!the!metal!does!not!play!a!direct!role! in! the! activity! of! the! osmocifens! but! serves! to! modulate! the! activity! of! the! organic! fragment! ? Tamoxifen.! A!number!of!osmium!carbonyl!clusters,!viz.,!Os 3 (CO) 10 (NCMe) 2 !2,!Os 3 (CO) 11 (NCMe)(µLH) +! 1'( and! Os 3 (CO) 9 (µLH)(µL?LC 6 H 5 O 3 )! 5,! were! found! to! exhibit! high! cytotoxicity,! and! they! appear! to! have! intracellular! sulfhydryl! residues! as! the! common! target.! This! can! be! understood! on! the! basis! that! osmium! is! a! soft! Lewis! acid;! it! binds! weakly! to! hard! Lewis! bases! such! as! acetonitrile

!. Fe and !. +. Ru-fe, !The!ability!to!form!the!quinone!methides!is!a!function!of!the!redox! potential!of!the!metal;!the!three!metallocifens!Os)!exhibited!similar!structural!and!physical! characteristics! but! very! different! antiproliferative! activity! (Table! 5.1).! The! ferrocifens! greatly! enhanced!the!cytotoxicity!of!Tamoxifen,!and!became!very!active!against!the!hormone!independent! (ERL)!breast!cancer!cells.!On!the!other!hand,!only!the!ruthenocifen!and!osmocifen!are!active!while! the! monophenol! and! diphenol! analogues! are! almost! inactive! against! the! breast! cancer! cells.! This! result!shows!that!the!cytotoxic!effect!of!the!metallocifens!not!only!came!from!the!metallocene!but! also! the! amine! chain;! and! this! effect! is! more! pronounced! for! the! ferrocene! series.! This! could! be! attributed!to!the!higher!redox!potentials!of!Ru!and!Os!?!oxidation!to!the!active!quinone!methides! was!more!difficult,!and!the!stability!of!these!were!also!lower.!Lastly,!the!senescence!effect!seems!to! be!an!important!characteristic!too, activity( Antiproliferative( Activity( Compound( Metal( (M)( ER+( ERE( Senescence( QM(formation( electrochemically( QM( stability