molecules Article Octakis(dodecyl)phthalocyanines: Influence of Peripheral versus Non-Peripheral Substitution on Synthetic Routes, Spectroscopy and Electrochemical Behaviour Glendin Swart , Eleanor Fourie * and Jannie C. Swarts Department of Chemistry, University of the Free State, Bloemfontein 9300, South Africa; 2015271865@ufs4life.ac.za (G.S.); swartsjc@ufs.ac.za (J.C.S.) * Correspondence: fouriee@ufs.ac.za; Tel.: +27-51-4012701; Fax: +27-51-4017295 Abstract: Non-peripherally octakis-substituted phthalocyanines (npPc’s), MPc(C12H25)8 with M = 2H (3) or Zn (4), as well as peripherally octakis-substituted phthalocyanines (pPc’s) with M = Zn (6), Mg (7) and 2H (8), were synthesized by cyclotetramerization of 3,6- (2) or 4,5-bis(dodecyl)phthalonitrile (5), template cyclotetramerization of precursor phthalonitriles in the presence of Zn or Mg, metal insertion into metal-free phthalocyanines, and removal of Mg or Zn from the phthalocyaninato coordination cavity. The more effective synthetic route towards pPc 8 was demetalation of 7. npPc’s were more soluble than pPc’s. The Q-band λmax of npPc’s was red-shifted with ca. 18 nm, compared to that of pPc’s. X-ray photoelectron spectroscopy (XPS) differentiated between N–H, Nmeso and Ncore nitrogen atoms for metal-free phthalocyanines. Binding energies were ca. 399.6, 398.2 and 397.7 eV respectively. X-ray photoelectron spectroscopy (XPS) also showed zinc phthalocyanines 4 and 6 have four equivalent Nmeso and four equivalent N–Zn core nitrogens. In contrast, the Mg phthalocyanine   7 has two sets of core N atoms. One set involves two Ncore atoms strongly coordinated to Mg, while Citation: Swart, G.; Fourie, E.; the other encompasses the two remaining Ncore atoms that are weakly associated with Mg. pPc’s 6, 7, Swarts, J.C. and 8 have cyclic voltammetry features consistent with dimerization to form [Pc][Pc+] intermediates Octakis(dodecyl)phthalocyanines: upon oxidation but npPc’s 3 and 4 do not. Metalation of metal-free pPc’s and npPc’s shifted all redox Influence of Peripheral versus potentials to lower values. Non-Peripheral Substitution on Synthetic Routes, Spectroscopy and Keywords: phthalocyanine; metal-free; zinc; magnesium; UV–vis; FTIR; NMR; XPS; cyclic voltammetry Electrochemical Behaviour. Molecules 2022, 27, 1529. https://doi.org/ 10.3390/molecules27051529 Academic Editor: Yongzhong Bian 1. Introduction Received: 11 January 2022 Phthalocyanines represent a class of chromophores, which consist of four isoindole Accepted: 19 February 2022 subunits (red fragment highlighted in Figure 1), tethered together by aza-bridges, resulting Published: 24 February 2022 in an 18 π-electron aromatic configuration [1]. Cyclization of isoindole fragments, in this manner, produces phthalocyanines, bearing a cavity that can accommodate ca. 70 elements Publisher’s Note: MDPI stays neutral of the periodic table. with regard to jurisdictional claims in Protons situated on peripheral positions (positions 2, 3, 9, 10, 16, 17, 23, and 24 of published maps and institutional affil- structure 1a in Figure 1) are simultaneously meta and para relative to the pyrrolic fragment iations. of the phthalocyanine. The properties of these protons differ from those of non-peripheral phthalocyanine protons (positions 1, 4, 8, 11, 15, 18, 22, and 25 of phthalocyanine 1b in Figure 1), and this positioning is always ortho relative to the pyrrolic fragment of the Copyright: © 2022 by the authors. phthalocyanine. The latter positions are more protected (or sterically hindered) than the Licensee MDPI, Basel, Switzerland. former in the presence of bulky R groups. As such, peripheral and non-peripheral protons This article is an open access article in 1a and 1b exist in chemically inequivalent environments. They are aromatic protons distributed under the terms and because of the aromaticity of the 18 π-electron phthalocyanine macrocycle. conditions of the Creative Commons The purpose of bulky periphery substituents R (Figure 1) or large axial ligands co- Attribution (CC BY) license (https:// ordinated to metal ions within the phthalocyaninato core (M in Figure 1) is to mitigate creativecommons.org/licenses/by/ the aggregation propensity of phthalocyanines, so that chemical and physical properties 4.0/). Molecules 2022, 27, 1529. https://doi.org/10.3390/molecules27051529 https://www.mdpi.com/journal/molecules Molecules 2022, 27, x FOR PEER REVIEW 2 of 18 Molecules 2022, 27, 1529 2 of 18 aggregation propensity of phthalocyanines, so that chemical and physical properties of tohfet hmeomnonmoemriec ripchpthathloaclyoacynai naitnoa tsopsepcieecsi ecsacna nbeb eefeffificiceinentltyl yhhaarvrveestsetedd ffoorr iindussttrriiaall or technological applications.. FFiiggurree 11.. SSttrruuccttuurreeo offn noonn-p-pereirpihpehrearlalylly(1 (a1)aa)n adnpde rpiperhieprhaellryal(l1yb ()1obc)t aokcitsa-skuisb-sstuitbustteitduptehdth pahlotchyaaloncinyeas-. nRin=esa.n Ry =s uaintyab slueitsaubblset situubesntitt.uTehnet. cTehnet rcaelnctroaolr cdoionradteindaatetodm at,oMm,, cMan, cbaen obnee oonfe aotf laeta lseta7s0t 7d0i fdfeifrfenr-t enletm eleenmtsenoftst hoef tpheer ipoedriicotdaibc ltea.ble. Apprrooprriiaattee aauggmeennttaattiioonnt otoa cahchieiveeves usiutaitbalbelpe hpthtahloacloycaynaineindee rdievraitvivaetivsoel usobliulibtyili(toyr (moro dmuoldatuelaatney aontyh oerthpehr ypshicyaslicoarl cohre cmhiecmalicparlo ppreorptye)rtcya)n cbane bbreo burgohutgahbto aubtobuyt sbuyb ssutibtsuttiitoun- toinont hoenp tehrei ppheerripyhoefrtyh eofa tnhneu alantneudlabteendz ebnenezreinnge sr,icnogms, pcloemxaptiloexnawtioitnh wa imthe taa lmceetnatlr ecewntirthe waxiitahl alxigiaaln ldigsantodsth toe tphhet hpahltohcayloacnyinaneicnoer ceo, roer, obry bcyh cahnagnignigngth tehen naatuturereo off tthhee ccoonnjjuuggaatteedd ππ--ssyysstteemm [[11]].. PPeerriipphheerraall aanndd//oorr nnoonn--ppeerriipphheerraall ssuubbssttiittuuttiioonn iiss aacchhiieevveedd bbyy eeiitthheerr aarroommaattiicc eelleeccttrroopphhiilliicc ssuubbssttiittuuttiioonn oorr ccyyccllooaaddddiittiioonn ttoo aa pprreeffoorrmmeedd uunnssuubbssttiittuutteedd pphhtthhaallooccyyaanniinnee oorr tthhrroouugghh tthhee ccyyccllootteettrraammeerriizzaattiioonn ooff tthhee aapppprroopprriiaatteellyy ssuubbssttiittuutteedd pprreeccuurrssoorr [[22]].. TThhee llaatttteerr ssttrraatteeggyy pprroovviiddeess mmoorree ccoonnttrrooll oovveerr tthhee nnuummbbeerr ooff ssuubbssttiittuueennttss aanndd pphhtthhaallooccyyaanniinnee iissoommeerrss ffoorrmmeedd dduurriinngg tthhee rreeaaccttiioonn [[22,,33]].. MMeettaall pphhtthhaallooccyyaanniinneess ccaann bbee pprreeppaarreedd tthhrroouugghh aa mmeettaall--tteemmppllaattee ddiirreecctteedd ccyyccllootteettrraammeerriizzaattiioonn bbeettwweeeenn aa pphhtthhaallooccyyaanniinnee pprreeccuurrssoorr,, ssuucchh aass pphhtthhaalloonniittrriilleess,, aannddc ocorrrersepsponodndinigngm meteatlasla slta[l4t ][.4I]n. cIencaen dancod- wcoo-rwkoerrskedresm doenmstornatsetdrattheids twhiitsh wthieths ytnhteh essyisntohfepseisr ipohf epraelrliypshuebrasltliytu tseudbostcittaukteisd(d oocdteackyils)(pdhotdheacloycl)ypahntihnaaltooczyinacn(iInI)at[o5-]. zMinect(aIlIa) t[i5o]n. Mcaentaallastoiobne cpane raflosrom beed poernfoarmpreed-e oxnis ati npgrem-exetisatli-nfrge empehtatlh-farleoec ypahnthinaelo, ctyharonuingeh, trherflouuxginh greifnluthxienpgr iens ethnec eproefsaenmcee toafl as amlte[t6a]l. sMalte [ta6]l.c Marebtoalx cyalarbteosxayrleatpesr eafreer rperdefoevrreerdm oevtearl mhaeltiadle hsaalsidmese taasl msoeutracle sso.urces. TThhee ddeellooccaalliisseedd,, ccoonnjjuuggaatteedd ππ--ssyysstteemm ooff aa pphhtthhaallooccyyaanniinnee ddeerriivvaattiivvee ccaann uunnddeerrggoo eexxcciittaattiioonn tthhrroouugghh pphhoototonn ininteteraractcitoionns,s r,erseusultlitnign gini ninitnetnesnes Qe -Qb-abnadn adbasobrspotripotnio mnamxiamxiam ina tihnet hraenrgaen ogfe coaf. 6c2a0. –672000– n70m0 (ntwmo( Qtw-boaQnd-b caonmdpcoonmenptosn, eQnt as,nQd xQand Qy, are observed forx y, are observed for metal- fmetal-free phthalocyanines) and a lower intensity Soret band absorptiorraeneg pehotfh3a2lo0c–y4a2n0innmes.) and a lower intensity Soret band absorption maxi nmmumax iimn uthme rinantghee of 320E–le4c2t0r incmfie. ld excitation causes metal-free phthalocyanines, or those containing a redox- silenEt lmecettraicll ifcieclde netxrcei,tatotionno rcmauaslelys mexehtaibl-iftreaet opthatlhoaflosciyxarniinnge-sb, aosre dth,oosne ec-oenletcatirnoinngr ead roex- dporoxc-seislseenst. mTewtaolliocf ctehnetsree, atore nooxrmidaaltliyo nexsh, iwbiht iale tothtael oref msixa irnidnger-baarseedre, donuec-teiolencstr[o7n]. reEdloecx- ptrrooccheesmseisc. aTlwanoa olyf stihseosfe saurieta obxlyidsaotilounbsle, wphhtihlea ltohcey raenminaeins,dweri tahrien rtehdeuscotlivoenns t[w7].i nEdleocwtroo-f cdhicehmloicraolm aentahlyansies, ooff tseunitraebvlyea sloflouubrleo pf hththeaslioxcyrianngi-nbeass, ewditrheidno txhceo suoplvleesnt[ 8w],inaldthoowu ogfh d1i7- cohfltohreompoetshsaibnlee, 1o8fteonn er-eevleeactlr foonurt roafn sthfeer spixr orcinesgs-ebsasoefda recaddomx ciuomuplterisp [l8e],d aelctkheorugphh t1h7a loof- tchyea pnoinses,ibCled 18P con,ew-eelercetroobns etrravnesdfeirn ptrhoecessoslevse onft aT cHadFm[9iu].mP thritphlael odceycakneirn pehsthbaelaorcinyganfionuer, 2 3 Cnodn2P-pc3e, rwipehreer oabl s2e-brvuetdy lionc ttyhleo xsoylvsiednetc ThHaiFn s[9h]a. vPehtbheaelnocsyhaonwinnesto bfeoarrmingc ofonudre nnsoend-ppehriapshes- earnadl 2e-xbhuibtyitlolicqtuyliodx-cyr ysisdtaelcbheahinasv ihoauvre[ 1b0e]e.n shown to form condensed phases and exhibit liquidS-ucbrystsittault bioenhaovniotuhre [p1e0r]i. phery and metalation have been shown to change solution phasSeuabgsgtriteugtaiotino no[n1 1th,1e2 ]p,ecraiupsheerdyi sacnodti cmmeetasolaptihoans ehbaevhea bveioenu rs[h1o3w],na lttoer cehlaenctgreo cshoelmutiicoanl pphroapsee ratgiegsre[1g4a]t,ioann d[11sh,1i2ft], tchaeuwsea dvieslceontgict hmfeosropQh-absaen bdeahbasvoiorputri o[1n3]m, aalxteimr eale[c1t5r]o.chUesminigcaal combination of these augmentations allows for the unique physical and chemical properties Molecules 2022, 27, x FOR PEER REVIEW 3 of 18 Molecules 2022, 27, 1529 properties [14], and shift the wavelength for Q-band absorption ma3xoifm18a [15]. Using a combination of these augmentations allows for the unique physical and chemical proper- ties of phthalocyanines to be fine-tuned. This process of fine-tuning allows phthalocya- of phthalocynaineinse tsot boeb uetfiilnisee-tdu nine da.reTahsi s upcrohc aes spohfofitonde-ytunnaimngica cllaonwcesrp thhtehraalopcyy (aPnDinTe)s [t1o6], bulk hetero- be utilised ijnunacretiaosns uocrghaansipc hsotlaord ycenlalsm [i1c7c]a, nocxeyrgtehne rraepdyu(cPtiDoTn) r[e1a6c],tibounl kcahteatleyrsoijsu [n1c8t]io, nonlinear optics organic sola[r19c]e,l lasn[d17 l]i,qouxiydg cernyrsetadlu dctiisopnlaryea tcetciohn ocalotagly s[i2s0[]1. 8], nonlinear optics [19], and liquid crystal disTphlaey styenchthneosliosg, yU[V20–]v. is spectrometry, and 1H NMR results for non-peripherally sub- The sysnttihtuesteisd, UocVt–avkiiss(sdpoecdterocmyle)ptrhy,thaanldoc1yHaNniMneR, 3re, saunldts iftosr zninocn--cpoeorirpdhineraatlelyd sduebrsivtia- tive 4, Scheme tuted octak1is,( hdaovdee cbyele)pnh rtehpaolortceyda n[3in].e C, 3y,calnicd viotsltzaimncm-ceotorryd oinf a3t eind ddiecrhivloartoivme e4t,hSacnhee m(DeC1M,◦ ) at 25 °C and have been rtehpaot rotefd 4[ 3i]n. Cdyicchlilcovrooelttahmanmeetry of 3 in dichloromethane (DCM) at 25 C and◦ (DCE) at 70 °C were presented. Tetrabutylammonium hex-that of 4 in adfilcuholorroopehthoasnpeha(DteC (E[N) a(tnB7u0) C][PwFer])e wpraess euntitleidse. dTe atsra ab suutyplpamorm4 6 tinongi eulmechtreoxlayflteu.- A limitation of orophosphathteis( [eNle( n ctBrouc)4h]e[PmFi6c]a)lw stausduyt iwlisaesd thasata psoutpepnotiratlins gweelreec trreoplyotret.edA vliemrsiutast iaonn Aofg/Ag+ reference this electrochemical study was that potentials were reported versus an Ag/Ag+ reference because, whbeencafuersreo,c wenheewn afesrardodceendea ws aans iandtedrenda larse afenr einncteer,nitawl raesfeforeunncdet, oito wvearsl afpouwnidth to overlap with the first rintgh-eb afsiersdt orxinidga-tbia − osne.dI noaxdiddaittiioonn,. PInF a−dadniitoionns,( fPrF6 om6 athneiosnusp (pforortmin gtheele scutrpoplyotreting electrolyte used) are knuosewdn) taorefo krnmoiwonn ptoa ifrosrwmi tihonca ptiaoinrsic w(oixthid ciasetido)nsipc e(coixeisd. iPshetdh)a slopceycaiensi.n Peh6t,hpael-ocyanine 6, pe- ripherally sruibpshtietruatleldy oscutab(sdtoitduetceydl )pohcttha(adloocdyeacnyaln)pinhatthoazlionccy(IaI)n, aSnchineamtoez1i,nwc(aIsI)p, rSevchioeumsley 1, was previ- isolated froomuaslpyh itshoallaotceyda nfrionme m ai xpthutrheaplroocdyuacneidnef rmomixatusrtea tpisrtoicdaul ccoendd fernosmat iao nst[a5t]i.sTtihcael condensation UV–vis spe[c5tr]o. sTchoep yU, 1VH–vNisM sRpeacntdromsceospopyh, a1Hse bNeMhaRv ioanudr wmeeresorpephoarste db.eThhaevimouetra lw-ferere reported. The derivative omfetthails-fcroeme dpelerxivwataivsen oft tshyinst hcoemsispelde,xa wndasn neoitth seyrnwtheeresisaendy, ealnedct rnoecihthemeri cwalere any electro- studies perfcohremmeidc.al studies performed. A H25C12 C12H25 H25C12 C12H25 C12H25 Li H25C12 N N C12HN 25 Zn(OAc) H2 25C12 N N N C12H25CN n-Pentanol n-Pentanol NH HN N Zn N 18 h, 110oC 4 h, 130oC CN N N20 % yield H C N N C N N25 12 12H25 89 % yield H25C12 C12H25 C12H25 2 H25C12 C12H25 3 H25C12 C12H25 4 H25C12 C12H25 B Zn(OAc) H C 2 N N25 12 CN NDMAE H25C12 C12H25 N Zn N 16 h, 130oC H25C12 C12H25 H25C12 CN N N N 11 % yield 5 6 Mg(OAc)2•4H2O Li, H 25 C12 C12H25 DBU, n-pentanol 16 nh -, p1 e 18 h, 130oC 1 n 0 o taC nol Pyridine, Py-HCl, o 39 % yield 10 % 20 h, 120 C yield 82 % yield H25C12 C12H25 H25C12 C12H25 N N Acetic acidN N N N H25C12 C12H25 n-Pentanol H25C12 C12H25 N Mg N NH HN o H25C12 C H 0.5 h, 130 C12 25 H25C12 C12H25 N N N 82 % yield N N N 7 8 H25C12 C12H25 H25C12 C12H25 Scheme 1. (TSocph, eAm) Sey 1n.t (hTeosips,o Af n) oSny-nptehreipshise oraf lnlyosnu-bpsetritiuptheedrpalhltyh saulobcsytaitnuinteeds. p(Bhothttaolmoc,yBa)nSiynnetsh. e(Bsios ttom, B) Synthe- of peripheralslyiss oufb sptietruitpehdeprhaltlhya lsoucbysatniitnuetse.dC pohnsthisatelonctywainthinXePs.S Creosnusltis,tednets cwribitehd XbPelSo wre, sNu-lbtsin, diensgcribed below, N- to Mg in 7 isbniontdsihnogw ton Masgf oinu r7e iqs uniovta slehnotwsynm ams feoturirc ebqounidvsa,lbenutt rsaytmhemr eatsrtiwc booindeqs,u bivuatl reantthseert saos ftwo inequivalent bonding intesreatcst ioofn bs.oDndMinAgE i=ntderimacettihoynlsa. mDiMnoAetEh a=n doilm, DeBthUyl=am1.8in-doieatzhaabnicoyl,c lDoB[5U,4 ,=0 ]1u.n8-ddeica-z7a-ebnicey, clo[5,4,0]undec- OAc = acetat7e-,ePnye,= OpAyrci d=i nacee. tate, Py = pyridine. Molecules 2022, 27, 1529 4 of 18 With this background, in the present work, the synthesis of 3, 4, 6, and the new metal- free and magnesium derivatives of 6 phthalocyanines 8 and 7, respectively, is presented. Special focus has been placed on the synthesis of 8, Scheme 1. Three different synthetic routes were employed. Cyclic voltammetric results of all phthalocyanines were obtained here in the common solvent THF and supporting electrolyte [N(nBu4)][B(C6F6)4]. This allows direct comparison and identification of electrochemical differences, as a result of different substitution patterns, peripherally vs. non-peripherally. The use of the supporting electrolyte [N(nBu4)][B(C6F6)4] is beneficial, as the B(C6F6) −4 anion is known to be inert to ion pair formation with cationic species [21]. All formal reduction potentials are here referenced vs. FcH/FcH+, and the internal reference, decamethylferrocene, has been chosen, which does not overlap/interfere with any phthalocyanine redox properties. Together with 1H NMR, UV–vis, and X-ray photoelectron spectroscopy (XPS), we highlight the influence peripheral versus non-peripheral substitution have on the spectroscopy and electrochemical properties of octakis(dodecyl)phthalocyanines. 2. Results and Discussion 2.1. Synthesis The precursor phthalonitrile 2, 3,6-bis(dodecyl)phthalonitrile was obtained from thio- phene using a four-step reaction sequence, as is described previously [3]. Thiophene was first lithiated with n-BuLi to form 2,5-dilithiumthiophene, which was treated in situ with 1-bromododecane to replace both lithium atoms with dodecyl substituents. Dimethyldioxi- rane was then used to oxidise 2,5-bis(dodecyl)thiophene to the corresponding thiophene- 1,1-dioxide (or sulfone). The five-membered sulfone ring was expanded to a six-membered benzene by means of Diels–Alder condensation with fumaronitrile to liberate, after SO2 elimination, phthalonitrile 2. Both the reaction sequence (Scheme S1) and experimental details of the synthesis of 2 may be found in the Supporting Information. Precursor 5, 4,5-bis(dodecyl)phthalonitrile, required no ring expansion procedures. It was synthesised from phthalimide using a modified five-step reaction sequence, as described in literature [22,23]. Electrophilic aromatic iodination of phthalimide, using elemental iodine and fuming sulfuric acid, was followed by imide ring opening in aqueous ammonia to yield 4,5-diiodobenzene-1,2-dicarboxamide. Subsequent dehydration with either trifluoroacetic anhydride or phosphoryl chloride forms 4,5-diiodophthalonitrile, the iodine atoms of which were replaced with dodecyne substituents in a follow-up modified Sonogashira coupling with 1-dodecyne. To obtain phthalonitrile 5, the alkyne groups were then converted to an aliphatic functionality, by means of catalytic hydrogenation, in the presence of palladium on carbon. Modified experimental conditions, as well as a detailed reaction sequence (Scheme S2), may be found in the Supporting Information. Metal-free non-peripherally substituted phthalocyanine 3 was synthesised under argon through cyclotetramerization of 2, using lithium pentoxide as nucleophilic initiator (Scheme 1). Lithium pentoxide was generated in situ through the addition of metallic lithium to warm pentanol. After acidic workup and column chromatography 3 was obtained in 20% yield as an air-stable dark green solid. Zinc phthalocyanine 4 was obtained as a blue solid, in 89% yield, after workup by refluxing 3 under dry and air-free conditions in n-pentanol, in the presence of anhydrous zinc acetate. Both 3 and 4 should be stored in a dark environment, as photodegradation of these compounds was observed on TLC plates, which were exposed to laboratory lighting for short periods of time. The peripherally substituted zinc phthalocyanine 6 was obtained by refluxing 4,5- bis(dodecyl)phthalonitrile 5 and anhydrous zinc acetate in dimethylaminoethanol, under dry and air-free conditions. This contrasts Ince’s method [5], where 6 was obtained as a side product from a statistical condensation between 5 and a differently substituted phthalonitrile. However, no metal-free derivative of 6, i.e., phthalocyanine 8 in Scheme 1, is known. Searching for a method to synthesise the metal-free peripherally substituted octakis(dodecyl) phthalocyanine 8, we noted that Cammidge and co-workers reacted two equivalents of Molecules 2022, 27, 1529 5 of 18 methyl magnesium bromide with 4,5-bis(2′-ethylhexyl)phthalonitrile. This yielded, in their hands, both magnesium phthalocyanine and tetrabenzotriazaporphyrin, with a ratio of 4:5 [24]. The central magnesium metal can then easily be removed to generate the metal-free species. Attempts of obtaining the magnesium phthalocyanine, 7, through this method failed, even if the number of equivalents of methyl magnesium bromide was lowered to 1. 1H NMR of the isolated green residue indicated that only the tetra- benzotriazaporphyrin had formed. Duplication of the synthetic procedure of 6, but by substituting anhydrous zinc acetate with magnesium acetate tetrahydrate, also failed to generate magnesium phthalocyanine 7. Only a dark yellow, unidentified oil was obtained after workup. However, as shown in Scheme 1, addition of the strong, hindered base, DBU (1.8-diazabicyclo[5,4,0]undec-7-ene), into the reaction mixture allowed for the generation of the magnesium phthalocyanine, 7, in 39% yield after workup. The lower reactivity of Mg(OAc)2.4H2O, compared to Zn(OAc)2, is likely attributed to water of crystallization, which impedes the ability of the acetate ion to act as a cyclisation initiator. Removal of the magnesium central metal from 7, with acetic acid at moderate tem- peratures (130 ◦C), generated the metal-free phthalocyanine 8, within 0.5 h in high (82%) yield, Scheme 1. Removal of the zinc central metal from 6 required more forcing conditions. Acetic acid was replaced with pyridine-HCl, and the reaction time increased to 20 h at 120 ◦C. Yields of 8 were, however, still high (82%). The direct approach to obtain 8 by refluxing 5 for 16 h in pentanol in the presence of lithium pentoxide, similar to the synthesis of 3, only resulted in 8 in 10% yield. A key aspect here is that 8 cannot be chromatographed. Poor solubility causes 8 to sit on the top of the column, as if it is an impurity, even if pure THF is used as eluent. Once this was realised, the direct route became viable because 8 can be purified by crystallisation from warm THF, see experimental section. To understand why the non-peripherally substituted metal-free phthalocyanine 3 is soluble, even in hexane, but the peripherally substituted metal-free phthalocyanine 8 is only weakly soluble in warm THF, one needs to look at the crystal structures of equivalent compounds. Cook solved the structure of a compound similar to 3; the substituent was not -C12H25 but -C6H13 [25]. While it is known that n-alkyl chains tend to lie in straight lines in the solid state, this is not possible for all substituents in non-peripheral positions. Here, adjacent alkyl groups will collide with each other if they are orientated linearly away from the phthalocyanine macrocycle. Cook found that four of the eight alkyl substituents are protruding away from the macrocycle and lie in the same plane as the macrocycle. Two more are approximately in the plane of the macrocycle. This is caused by rotation about C–C bonds to allow some of the side chain’s C-atoms to be above the macrocycle plane, with some others below it. The last two side chains rotated in such a way that it points perpendicularly away from the macrocyclic plane; one points up and the other down. These two side chains act as spacers that push adjacent macrocycles apart. The distance between macrocyclic planes is 8.5 Å. This implies a very weak core:core interaction and explains the good solubility of non-peripherally substituted compounds, such as 3. It will be easy for solvent molecules to diffuse between macrocycle cores, break any of the weak interactions that exist between them, and ultimately dissolve the phthalocyanine. In contrast, the alkyl substituents in peripherally substituted phthalocyanines, such as 8, do not have to rotate in a way that they end up perpendicular to the macrocyclic plane. Phthalocyanine macrocycles of octakis peripherally substituted compounds were, therefore, found to be much closer to each other, only 3.4–3.6 Å [5,26]. Core:core interactions are much stronger, and solvent molecules do not break these interactions easily in the absence of heat (8 was only soluble in THF at 60 ◦C). We conclude that the most effective way of obtaining peripherally substituted metal- free phthalocyanine 8 is by first synthesizing the magnesium derivative 7, followed by demetalation. Molecules 2022, 27, 1529 6 of 18 2.2. 1H NMR For metalated phthalocyanines, the non-peripheral hydrogens of 6 and 7 have 1H NMR resonances at 9.23 and 9.25 ppm, respectively, in THF-d8, while the 1H NMR resonance of peripheral hydrogens of 4 is at 7.88 ppm, also in THF-d8. This drift of ca. 1.36 ppm is the result of the structural differences between the peripheral and non-peripheral complex. The non-peripheral aromatic hydrogens of phthalocyanines 6 and 7 are sterically hindered by the peripheral dodecyl groups (Scheme 1). The peripheral hydrogens of 4 are more exposed (“naked”) and less deshielded. The influence of metalation on the resonance position of aromatic protons is demon- strated when one compares the aromatic proton resonances of 4, 6, and 7 with the corre- sponding resonances of 3 and 8. In the peripherally substituted compound series 6, 7, and 8, metalation caused a deshielding (movement of resonances to larger ppm values) of 0.19 (Zn) and 0.21 ppm (Mg) in THF-d8, while for non-peripherally substituted compounds, metalation had almost no effect. The aromatic proton resonance of 3 and 4 were both observed within the range of 7.87–7.88 ppm, despite being recorded in different solvents (CDCl3 for 3; THF-d8 for 4). The difference in dodecyl substitution pattern also had an effect on the 1H NMR reso- nance position of the “benzylic” methylene protons (i.e., protons of the CH2 groups bound directly to the phthalocyanine core). Changing from a non-peripheral to a peripheral sub- stitution pattern shifted the benzylic CH2 resonance of metal-free phthalocyanine 8 upfield by ca. 4.45 − 3.24 = 1.21 ppm, compared to the same resonance of 3, while this resonance of the metalated peripherally substituted derivatives 6 and 7 experienced an upfield shift of ca. 4.62− 3.26 = 1.36 ppm, compared to that of 4. Zinc insertion into the phthalocyanine core had only a small upfield influence on the benzylic CH2 resonance position of the non-peripherally substituted compound series 3 and 4 (4.62 ppm − 4.45 ppm = 0.17 ppm). In the peripherally substituted compound series, 6, 7, and 8, metalation had no effect on the benzylic CH2 resonance. For these three complexes, the benzylic proton resonance position was virtually unaltered at 3.24–3.26 ppm. Other aliphatic resonance positions were at expected positions and are documented in the experimental section. 1H NMR spectra may be found in the Supporting Information (Figure S9–S13). 2.3. FTIR–ATR and UV–Vis Spectroscopy Successful cyclotetramerization of phthalonitriles 2 and 5 into phthalocyanines 3, 6, 7, and 8 is reflected by the absence of the CN stretching vibration at 2229 cm−1 in the phthalocyanine Fourier transform infra-red attenuated total reflectance (FTIR–ATR) spectra, Supporting Information, Figure S14. FTIR–ATR spectra of the metal-free phthalocyanines 3 and 8 differ from those of the metalated phthalocyanines 4, 6, and 7 in that they show an additional stretching vibration at 3294 and 3358 cm−1, respectively. These vibrations are characteristic of the N–H bond within the phthalocyanine core. Figure 2 contains the UV–vis spectra for 3, 4, 6, 7, and 8 recorded in THF. Supporting Information Figures S15–S19 shows UV–vis spectra for these compounds at different concentrations. Poor solubility of 8 required that its spectrum be recorded at 60 ◦C, while other spectra could be recorded at 25 ◦C. Results extracted from these UV–vis spectra are summarised in Table 1. Table 1. Q-band λmax and logε data for 3, 4, 6, 7, and 8. λ amax/nm (logε) Compound Q Qx Qy 2HPc, 3 - 694 (5.01) 725 (5.08) ZnPc, 4 698 (5.31) - - ZnPc, 6 679 (5.29) - - MgPc, 7 681 (5.50) - - 2HPc, 8 - 668 (5.20) 704 (5.25) a ε = extinction coefficient in units of M−1 cm−1. Molecules 2022, 27, x FOR PEER REVIEW 7 of 18 Table 1. Q-band λmax and logε data for 3, 4, 6, 7, and 8. λmax/nm (logε) a Compound Q Qx Qy 2HPc, 3 - 694 (5.01) 725 (5.08) ZnPc, 4 698 (5.31) - - ZnPc, 6 679 (5.29) - - MgPc, 7 681 (5.50) - - 2HPc, 8 - 668 (5.20) 704 (5.25) a ε = extinction coefficient in units of M−1 cm−1. The electronic spectra of 3 and 8 have two absorption maxima in the Q-band region, Figure 2. This result is attributed to the D2h compound symmetry. For 3, the Q-band com- ponents are separated by Δλ = λmax Qy − λmax Qx = 31 nm, while, for 8, the separation is Δλ = λmax Qy − λmax Qx = 36 nm. Phthalocyanines 4, 6, and 7 have D4h symmetry. As a result, only Molecules 2022, 27, 1529 one Q-band absorption maximum is observed. D4h symmetry differs from D2h symmetr7yo f 18 in that the lowest energy singlet state is degenerate, causing the Qx and Qy components to merge into a single absorption maxima [4]. FiguFrieg u2.r e(L2e.f(tL) eUfVt)–UvVis– svpisecstprae cotrf apohfthpahltohcaylaonciynaensi 3n,e 4s,3 6,,4 7,,6 a,n7d, a8n, dre8c,orredceodr dined TiHnFT. HThF.eT shpecstpruecmtr um of 8 owf a8s wreacsorrdeceodr adte 6d0a °tC6; 0al◦l Co;thaelrl osptheecrtrasp wecetrrea rweceorrederedc oatr d2e5d °Ca.t D25ot◦teCd. lDinoetste hdiglhinliegshht itghhel irgehdt- the shiftriendg- sehffieftcitn ogf enffoenc-tpoefrinpohne-rpael rdipohdeercayll dsuobdsetciytulesnutbss. tTithuee nYt-sa.xTish reepYr-easxeins trse pmroelsaern etsxtminocltaiorne xctoienfc-tion ficiecnotes fifinc iuennittss of M −1 cm−1in units of M. (−R1igcmht−) 1B.e(eRri–glahmt)bBeeret rl–alwam, Abe =r tεlCawl, ,isA v=alidC lf,oirs tvhε ael iQd-fboarntdh efoQr -ablal ncdomfo-r all pounds, at least up to the indicated concentrations at the recording temperature. compounds, at least up to the indicated concentrations at the recording temperature. For Tmhetealle-fcrteroe npichtshpaelcotcryaaonfin3easn, dch8ahnagvinegt wdodaebcsyolr pstuibosntimtuaexnitms afrionmth peeQri-pbhaenrdalr etgoi on, nonF-pigeurirpeh2e.raTl hpiossriteisounlst risedasthtriifbtsu ttheed Qtox λthmeax Dby2h Δcλomaxp Qox u= nλdmasx yQxm, 3 m− eλtmrayx. QxF, 8o =r 63,94th −e 6Q68-b =a nd 26 ncmom apnodn Qeny tλsmaarxe bsye pΔaλrmaatxe Qdy b=y λ∆maλx Q=y, λ3 m−a λx mQayx Q−y, 8λ =m a7x2Q5x −= 70314 n= m21, wnmhi l(eT,afbolre8 1, )t.h Tehsee pnaorna-tion periipsh∆eλra=l λsmuabxsQtiytu−tioλnm apxaQtxte=rn3 6rendmsh. iPfths ththaelo czyinacn-icnoensta4i,n6i,nagn dph7thhaalvoecyDa4nhinsey mQm-beatrnyd. As a result, only one Q-band absorption maximum is observed. D4h symmetry differs from D2h symmetry in that the lowest energy singlet state is degenerate, causing the Qx and Qy components to merge into a single absorption maxima [4]. For metal-free phthalocyanines, changing dodecyl substituents from peripheral to non-periphe -ral positions redshifts the Qx λmax by ∆λmax Qx = λmax Qx, 3 − λmax Qx, 8 = 694 − 668 = 26 nm and Qy λmax by ∆λmax Qy = λmax Qy, 3 − λmax Qy, 8 = 725 − 704 = 21 nm (Table 1). The non-peripheral substitution pattern redshifts the zinc-containing phthalocyanine Q-band maximum of 4 by ∆λmax = λmax 4 − λmax 6 = 698 − 679 = 19 nm, compared to the peripheral substitution pattern of 6. This renders 4 a stronger candidate for photodynamic therapy than 6, as light achieves deeper tissue penetration at this wavelength [27]. Adherence of the Q-bands to the Beer–Lambert law (Figure 2) implies that all ph- thalocyanines remain unaggregated up to at least 6 µM in THF at the spectrum recording temperature. Figures S16–S20 in the Supporting Information show that the Soret band also follows the Beer–Lambert law. Q-band molar extinction coefficients of octa-substituted alkoxy and thioalkyl metal-free phthalocyanines have previously been reported, within the range of 41,100–135,600 M−1 cm−1, while their zinc derivatives have Q-band ε-values between 139,100 and 248,800 M−1 cm−1 [15]. These literature value ranges are comparable with that obtained for the octa-dodecyl metal-free Molecules 2022, 27, x FOR PEER REVIEW 8 of 18 maximum of 4 by Δλmax = λmax 4 − λmax 6 = 698 − 679 = 19 nm, compared to the peripheral substitution pattern of 6. This renders 4 a stronger candidate for photodynamic therapy than 6, as light achieves deeper tissue penetration at this wavelength [27]. Adherence of the Q-bands to the Beer–Lambert law (Figure 2) implies that all phthal- ocyanines remain unaggregated up to at least 6 µM in THF at the spectrum recording temperature. Figures S16–S20 in the Supporting Information show that the Soret band also follows the Beer–Lambert law. Q-band molar extinction coefficients of octa-substituted alkoxy and thioalkyl metal- free phthalocyanines have previously been reported, within the range of 41,100–135,600 M−1 cm−1, while their zinc derivatives have Q-band ε-values between 139,100 and 248,800 M−1 cm−1 [15]. These literature value ranges are comparable with that obtained for the octa- dodecyl metal-free (121,000 ≤ ε (Qy) ≤ 177,000 M−1 cm−1) and zinc phthalocyanines (193,000 ≤ ε ≤ 204,000 M−1 cm−1) presented in this work. Molecules 2022, 27, 1529 8 of 18 2.4. X-ray Photoelectron Spectroscopy Figure 3 displays the X-ray photoelectron spectra (XPS) of the nitrogen 1s, magne- siu(m12 11,0s0,0 a≤ndε (zQiyn)c≤ 21p7 7e,0n0v0eMlo−p1 ecms −fo1)ra nadll zpinhctphhatlhoacloycayanniines .( 1D93a,0t0a0 e≤xεtr≤ac2t0e4d,0 0f0roMm− 1Fcimg−u1r)e 3 is sumprmesaernitseeddi nint hTiasbwleo r2k.. 2.4E. aXc-hra pyhPthhoatoleolcecytaronninSep ehctarsos fcoopuyr meso nitrogen atoms (Nmeso) and four core nitrogens. For metal-free phthalocyanines (3 and 8), two of the core nitrogens are bound to hydrogen atoms (FNig–uHre),3 displays thesium 1s, and wzhinilce2 tpheen rveem Xa-irnadyephlopes forr e oxtioselectron spectra (XPSall pt hatsh acloorcey nanitirnoegs.enD acto )mofptohneennitroa extractetds, N gen 1, so, fm thagenfromcoreFigure 3 p e- ishthal- ocysaunminmea rmisaecdroincyTacblele. 2. A: N 1s B: N 1s C: Mg 1sNmeso 50 cps MgPc, 7 MgPc, 7 200 cps 1308 1305 1302 1299Mg-N Ncore Binding energy /eV 2HPc, 8 400 cps ZnPc, 6 D: Zn 2p1/2 Zn 2pH-N N 3/2meso N Nmeso ZnPc, 6 core Zn-N 500 cps 2HPc, 3 ZnPc, 4 ZnPc, 4 402 400 398 396 394 402 400 398 396 394 1055 1045 1035 1025 1015 Binding energy /eV Binding energy /eV Binding energy /eV FigFuirgeu r3e. 3(L. e(Lfte,f tA, A) N) Nitirtoroggeenn 11ss XXPPSS eennvveeloloppeesso fofm meteatl-aflr-eferepeh pthhatlhocayloacnyinaensin3easn 3d a8.n(dM 8i.d (dMlei,dBd) le, B) NitNroitgreonge 1ns1 Xs PXSP Senenvveeloloppeess ooff mmeettaalalatetdedp hpthhtahloaclyoacnyiannesin4e,s6 ,4a, n6d, a7n. (dR 7ig. h(Rt, iCg)hMt,g C1)s Mengv e1lso peenvfoerlo7.pe for 7. (R(Riigghhtt,, DD)) ZZiinncc2 2ppe nevnevleolpoepsefso rfoprh tphhatlohcaylaonciynaens i4naens d4 6a.nInd a6l.l Isnp eacltlr as,peexcpterari,m eexnptearlipmheontotealle cpthroontoelec- tronli nleins easre abrleu eb,launed, sainmdu lsaitmeduGlaatuesds iaGnapuhsositaoenl epcthroontoleinleecstarroenr eldin. eFso raArea rneddB. ,Fbolar cAk lianneds rBep, rbeslaecnkt lines reperiethseenr tth eeitshimeru tlahtee dsiNm–uHla, Nte–dM Ng–, oHr,N N––ZMn pgh, ootro Nele–cZtrno nplhinoetso,eglreecetnrolinn elisnreeps,r egsreenetns ilminuelsa treedpNremseesno t sim- ulaptehdo tNoemleescot prohnoltioneelse,cwtrhoinle ,lifnoresA, wanhdilBe,( ftoopr )A, o arnandg Be l(itnoeps)r,e oprraensegnet lNincoerse rpehporteoseelenctt rNoncorlei npehso. tIoneBle, ctron linefso.r I7n, tBhe, ffooru r7M, tgh–eN fobuorn dMsgar–eNn obtocnodnssi daerere ndoetq cuoivnasliednet,rseede Secqhueimvael1e.nRt,a stheeer ,Sdcuheemtoeth 1e. sRmaatlhl esriz, edue to theo sfmthaellM sgiz2+e coaft iothne, thMegy2a+ rceactoionnsi,d tehreedy aasrtew cooinnseiqdueivreadle natss etwts oo fiMnegq–uNivbaolnednitn gseitnst eorfa cMtiogn–sN. O bnoending intesreatcisticoonnss.i dOenreed ssettr oisn gcobnosniddienrgeidn tsetrraocntigo nbso(nthdeinbgla cinktMerga–cNtiopnhso t(othelee cbtlraocnkl iMneg),–wNh iplehtohteoeoltehcetrrsoent line), whiislec otnhsei doetrheedrt osebte iws ecaoknbsiodnedriendg itnot ebreac wtioenask( tbhoenodrainngge ipnhteortaoeclteioctnros n(tlhinee olarbaenllgeed pNhcorteo).electron line labelled Ncore). Table 2. Binding energies (BE) and atomic % for the nitrogen 1s, zinc 2p, and magnesium 1s envelopes. Compound Nmeso 1s BE/eV Metal dNe-rMiv;aNtivesB E(4/e Vand 6) Mdieftfaelr1, sionr t2hpiBs Er/eeVgard, in thcore Moalet caullla rfSotuoric hcoiorme entriytreogens are (Atomicsy%m) metrically (Acotoomrdicin%a)ted to the m(eAttaolm ciecn%t)re (N-M). EExxppeerriimeenntatla(lT hNeo 1rest icXaPl)S spectra 3 (M = 2H) 398.3 (1c.7o7u) ld not 3r9e9s.8o(l0v.8e8 )t;h3e9s7e.9 d(0i.8ff8e)rent nitrogen- atom types Nunam:Nbig:Nuous=ly4 :2(:F2ifg(u4:r2e:2 )3g). How-meso H core 4 (M = Zn) 397.7 (2e.2v5e) r, the bind3i9n8.g6 (2e.n25e)r;g- ies (BE1)0 4f4o.6r a;t1h0e2s1e.6 bd(i0f.f5e5r)ecnt nNimtresoog:NeZnns:Z cno=u4l:d4: 0.b9e8 f e(4s:t4i:m1)agted by 6 (M = Zn) 397.9 (2.39) 398.7 (2.39); - 1044.7 a; 1021.6 b (0.59) c N f gmeso:NZn:Zn = 4:4:0.99 (4:4:1) f 7 (M = Mg) 398.0 (2.18) 398.9 (1.09); 396.7 (1.09) 1303.0 d (0.51) Nmeso:NZn:Ncore:Mg = 4:2:2:0.94(4:2:2:1) g 8 (M = 2H) 398.0 (1.23) 399.2 (0.61); 397.5 (0.61) - Nmeso:NH:Ncore = 4:2:2 f (4:2:2) g a Zn 2p ; b Zn 2p ; c1/2 3/2 of Zn 2p d3/2 Mg 1s; e of the indicated atoms only; f experimental atom ratios; g theoretical atom ratios. Each phthalocyanine has four meso nitrogen atoms (Nmeso) and four core nitrogens. For metal-free phthalocyanines (3 and 8), two of the core nitrogens are bound to hydro- gen atoms (N–H), while the remainder exist as core nitrogen components, Ncore, of the phthalocyanine macrocycle. Metal derivatives (4 and 6) differ, in this regard, in that all four core nitrogens are symmetrically coordinated to the metal centre (N-M). Experimental N 1s XPS spectra could Molecules 2022, 27, 1529 9 of 18 not resolve these different nitrogen atom types unambiguously (Figure 3). However, the binding energies (BE) for these different nitrogens could be estimated by simulating the experimental spectra through Gaussian curve fitting (Table 2). Three Gaussian curves, with a fixed area ratio of 1:2:1, were used for metal-free phthalocyanines, while two Gaussian curves, with a fixed area ratio of 1:1, were used for the metal derivatives 4 and 6. The N 1s envelope of the magnesium derivative 7 differed from those of the zinc derivatives 4 and 6, in that, for 7, similar to the metal-free derivatives, two different photoelectron lines needed to be simulated to replicate the Mg–Ncore experimental photoelectron lines. To explain this, it is noted that Zn2+ ions have an ionic radius of 0.74 Å, while Mg2+ ions have an ionic radius of 0.65 Å [28]. This, together with the XPS result, showing two sets of Mg–N photoelectron lines of equal intensity, is consistent with an asymmetric bonding pattern, as shown for 7 in Scheme 1. Moving from a peripheral to non-peripheral substitution pattern in metal-free ph- thalocyanines 3 and 8 increases the binding energy of Nmeso, N–H, and Ncore by 0.3 eV (an insignificant change, a BE change of ≥0.4 eV is considered significant), 0.6 eV, and 0.4 eV, respectively (the latter is on the extreme edge of being significant). For zinc phthalocya- nines 4 and 6, the change in substitution pattern has no significant influence on the binding energy for Nmeso and Ncore atoms (0.2 eV and 0.1 eV difference, respectively, Table 2). Zinc insertion in the non-peripheral series (3 and 4) has a marginally significant influence on the binding energy of Nmeso (397.7 − 398.3 = −0.6 eV), whereas both zinc and magnesium insertion into the peripheral series (i.e., comparing 8 with 6 and 7) has a negligible Nmeso binding energy difference. No significant XPS photoelectron line shifts are noted for the Zn 2p envelope, when comparing the non-peripherally (4) and peripherally (6) substituted zinc phthalocyanines (Figure 3, Table 2). 2.5. Electrochemistry Selected cyclic voltammograms (CVs) of phthalocyanines 3, 4, 6, 7, and 8 are displayed in Figure 4. Cyclic voltammetric data, applicable to these CVs, are summarised in Table 3. Due to the poor solubility of especially 8, CVs of all phthalocyanines were recorded in tetrahydrofuran (THF), either at 60 (only 8) or 25 ◦C (all other phthalocyanines). The cyclic voltammetry of 3 was also studied in dichloromethane (DCM) at 25 ◦C. Supporting Information Figures S20–S24 and Tables S1–S6 contains CVs and data at different scan rates. Electrochemical reversibility for one-electron transfer processes is characterised by ∆Ep = Epa − Epc = 59 mV [29]. All redox processes labelled A (anodic waves), I, and II (cathodic waves) for 3, 4, and 6–8 exhibit quasi electrochemical reversibility at slow scan rates, with 78 < ∆Epa < 135 mV (Table 3), but approach chemical reversibility (i.e., current ratios approached unity) with 0.83 < ipa/ipc < 1.00. In the THF potential window, only one of the two possible oxidation couples, wave A, was observed. As is well-known and -documented in literature [3,7,15], these phthalocyanine ring-based redox processes are all one-electron transfer processes. In this study, we report the linear sweep voltammetry (LSV) of compounds 3, 4, 6, 7, and 8 in Figure 4. The LSV show that the number of electrons transferred is the same for the observed oxidation and reduction waves; since it is known that the phthalocyanines ring-based processes are one-electron processes, it can also be extrapolated to all main waves of the present compounds studied. In the case of compound 8, the combined wave Aa and Ab gives an LSV wave of equal size to that of the other one-electron reduction wave. The LSV of the second reduction wave, wave II, is not always shown, since decomposition in many cases occurred on LSV time-scale, and wave II could not be observed on the LSV scans. Additionally, the peak current (ip) values of ring-based processes are all of approximately equal size, as can be seen from Figure 4 and Table 3. Peak currents are the analytical quantity measured for concentration in the Randles Cevcik equation. Together with the LSV results, peak current values are, therefore, also mutually consistent with all ring-based oxidation and reduction waves being one-electron transfer processes. MoleMcuolleesc u2l0es222,0 2227, 2x7 FOR PEER REVIEW 10 of 18 , , 1529 10 of 18 FigFuigruer 4e. 4L. eLfte: fCt:yCclyic lvicolvtoamltamomgoragmrasm (sC(VCsV) so)f otfheth iendinicdaicteadte dphpthtahlaolcoycaynainiense sata at ascsacna nrartaet eofo 1f 00 mV10/0s minV T/HsFin oTr HfoFr o3r ofnorly3, oin lDy,CinMD aCt M25a °tC2 5u◦nClesusn oletshseorwthiesrew inisdeiicnadteicda.t eSdel.eScetleedc tleindelainr esawr eswepe evpolt- amvmolotagmrammosg (rLamSVss()L, SreVcso),rdreecdo radt ead sactana sracaten orfa t1e mofV1/sm, aVr/e sa,lasroe sahlosowsnh.o Rwignh. tR: iCgVhts: oCfV 4s aonfd4 6a natd s6can rataetss coafn 5r0a (tsems oafll5e0st( scmuarrlleensttsc)u, r1r0e0n,t s2)0,01,0 300, 02,0 04,0300, 0a,n4d0 05,0a0n dm5V0/0s m(bVig/gse(sbti gcguersrtencutsr)r eint sT)HinF TaHt F25a t°C. Ins2e5r◦tsC: .SIqnusearrtes :wSaqvuea vreowltaamvemvoogltraamm (SoWgrVam) o(fS tWheV f)irosftt rhiengfi-rbsat sreindg o-bxaidseadtioonxi odfa 6ti,o rnecoofr6d,erdec aotr 2d0e dHz, in aTtH20F Hatz 2,5i n°CT,H hFigahtli2g5ht◦iCng, hbiegthtelirg rhetsinoglubtieotnte rbertewsoeleunti ownavbeestw Aeae annwd aAvbe sanAd lainnedarA swaenedp lvinoeltaarm-a b moswgreaempsv (oLltSaVmsm) oofg 4r,a minsdi(cLaStVinsg) othfe4 ,reinladtiicvaet innugmthbeerr eolfa teilveectnruonmsb ienrvooflveeledc tirno neascihn vroedlvoexd pinroecaecshs. redox process. Electrochemical reversibility for one-electron transfer processes is characterised by ΔEp = Epa − Epc = 59 mV [29]. All redox processes labelled A (anodic waves), I, and II (ca- thodic waves) for 3, 4, and 6–8 exhibit quasi electrochemical reversibility at slow scan rates, with 78 < ΔEpa < 135 mV (Table 3), but approach chemical reversibility (i.e., current ratios approached unity) with 0.83 < ipa/ipc < 1.00. In the THF potential window, only one Molecules 2022, 27, 1529 11 of 18 Table 3. Peak anodic potentials, Epa, peak potential differences, ∆Ep, formal reduction potentials, E◦′, peak anodic or cathodic currents, ipa and ipc, respectively, and current ratio, ipc/ipa or ipa/ipc for the 100 mV/s scan rate redox couples, indicated in Figure 4. Wave E /V ∆E /mV a E◦′/V i /µA i /i Wave E /V ∆E /mV a E◦′pa p pa pc pa pa p /V ipa/µA ipc/ipa Decamethylferrocene (THF) Ferrocene (THF) - −0.488 76 −0.527 6.00 0.96 - 0.039 78 0.000 10.80 0.98 Decamethylferrocene (DCM) Ferrocene (DCM) - −0.575 74 −0.614 5.00 0.98 - 0.035 70 0.000 6.50 0.96 3 (2H, non-peripheral, DCM) ∆E◦′HL = 1.531 V b 8 (2H, peripheral, THF) ∆E◦′HL = 1.562 V b A 0.136 97 0.088 4.75 1.00 Aa 0.227 f 111 0.172 1.56 0.83 B 0.726 143 0.655 c 3.38 0.56 Ab 0.416 f 98 0.367 1.80 0.83 I −1.396 93 −1.443 4.25 d 0.97 e I −1.326 127 −1.390 3.44 d 0.82 e II −1.754 92 −1.800 3.13 d 0.96 e II −1.785 135 −1.853 2.50 d 1.00 e 3 (2H, non-peripheral, THF) ∆E◦′HL = 1.590 V b 6 (Zn, peripheral, THF) ∆E◦′HL = 1.657 V b A 0.221 99 0.172 3.40 0.90 Aa 0.067 f 86 0.024 1.90 0.93 I −1.364 107 −1.418 3.40 d 0.88 e Ab 0.181 f 78 0.142 1.67 1.00 II −1.716 121 −1.777 3.40 d 0.88 e I −1.578 113 −1.633 3.10 d 0.85 e 4 (Zn, non-peripheral, THF) ∆E◦′ bHL = 1.673 V 7 (Mg, peripheral, THF) ∆E◦′HL = 1.705 V b A 0.105 105 0.053 3.60 0.97 A 0.080 135 0.012 2.40 0.96 I −1.556 128 −1.620 2.60 d 1.00 e I −1.646 95 −1.693 1.90 d 0.95 e a ∆Ep = Epa − Epc. b ∆E◦′ ◦′ ◦′ ◦′HL = E wave A (or Aa) − E wave I. ∆E HL = electrochemical HOMO-LUMO gap. c Strictly speaking, the Nernst equation, and equations derived therefrom, only hold true for electrochemically reversible processes, i.e., those that exhibit ∆Ep approaching 59 mV. d Actually ipc. e Because current ratios are defined as ireverse scan/i fforward scan, this is actually ipa/ipc. Due to poor peak resolution, values are only approximations. The peripherally substituted phthalocyanines 6 and 8 display CV features consistent with dimerization, as wave A is split into two components, Aa and Ab, of approximately equal intensity, with ∆E◦′ ◦′ ◦′Aa,Ab = E Aa − E Ab = ca. 195 mV for 8 or 118 mV for 6 (Table 3 and Figure 4) [30,31]. Wave A, of the peripherally substituted Mg complex 7, displays weak evidence of dimerization (see enlarged CV in Supporting Information, Figure S24), but the resolution between Aa and Ab is too poor to assign component potentials and currents. As a result, Table 3 only reports observed peak currents for this phthalocyanine. Peak splitting into two wave A components for the non-peripheral complexes 3 and 4 is not observed. To understand why peripherally substituted phthalocyanines exhibit dimerization features in wave A, but non-peripherally substituted derivatives do not, consideration of the structural differences between peripherally and non-peripherally sub- stituted complexes, as described at the end of Section 2.1, are instructive. From the crystal structure of non-peripheral octakisalkylphthalocyanine complexes, inter-macrocyclic dis- tances are ca. 8.5 Å [25], while, for peripheral substituted complexes, it is about 3.6 Å [5,26]. The stronger core:core interactions that exist in peripherally substituted phthalocyanines, which result from a closer inter-macrocyclic distance, imply that oxidized phthalocyani- nato species having a positive charge (i.e., they are electrophilic) may easily form dimeric intermediates with their neutral (i.e., unoxidized and nucleophilic) counterparts, see Scheme 2. Phthalocyanine 3 was soluble enough in dichloromethane (DCM) to allow cyclic voltammetry therein. The solvent window of DCM has a larger positive potential limit than that of THF. This allowed for the observation of the second one electron, ring-based oxidation of 3, wave B (Figure 4). This second anodic process is both electrochemically and chemically irreversible, with ∆Ep = 143 mV and ipc/ipa = 0.56, Table 3. Molecules 2022, 27, x FOR PEER REVIEW 12 of 18 consideration of the structural differences between peripherally and non-peripherally substituted complexes, as described at the end of Section 2.1, are instructive. From the crystal structure of non-peripheral octakisalkylphthalocyanine complexes, inter-macrocy- clic distances are ca. 8.5 Å [25], while, for peripheral substituted complexes, it is about 3.6 Å [5,26]. The stronger core:core interactions that exist in peripherally substituted phthal- ocyanines, which result from a closer inter-macrocyclic distance, imply that oxidized phthalocyaninato species having a positive charge (i.e., they are electrophilic) may easily form dimeric intermediates with their neutral (i.e., unoxidized and nucleophilic) counter- parts, see Scheme 2. Phthalocyanine 3 was soluble enough in dichloromethane (DCM) to allow cyclic volt- ammetry therein. The solvent window of DCM has a larger positive potential limit than that of THF. This allowed for the observation of the second one electron, ring-based oxi- dation of 3, wave B (Figure 4). This second anodic process is both electrochemically and chemically irreversible, with ΔEp = 143 mV and ipc/ipa = 0.56, Table 3. Scheme 2 illustrates an electrochemical mechanism related to the results that were obtained. From Scheme 2, several observations can be made. For metal-free phthalocya- nines 3 and 8, changing from non-peripheral substituents to a peripheral substitution pat- tern decreased the E°′ of cathodic wave II by ΔE°′wave II = E°′8, wave II − E°′3, wave II = −1.853 − (−1.800) = −0.053 V. Contrary to wave II, the E°′ for cathodic wave I of the peripherally substituted compound 8 increased slightly with 28 mV, when compared to the non-pe- Molecules 2022, 27, 1529 ripheral derivative 3. The first oxidation wave of the peripherally substituted meta12l-ofrfe1e8 phthalocyanine (Aa of 8) had the same E°′ as that of the non-peripheral complex (A of 3), with E°′ = 0.172 V vs. FcH/FcH+. Scheme 2. Proposed electrochemical mechanism consistent with the observed redox proc esses for 3S,c4h,e6m, e7 ,2a. nPdro8p.osNedo ne-lpeectrriopchheermalliycasl umbestcihtuanteidsmp hcothnasliostceynatn winieths tahree oabsssoecrviaetded rewdiotxh pbrroacceksestess (f[o])r, w3, h4e,r e6a, s7p, earnidp h8e. rNalosnu-bpsetritipuhteedrapllhyt hsaulbosctyitauntiende spahrtehanlootc.yWanaivneesB awrea saossnolyciaotbesde rwveitdh fborra3ckinetDs C([M]), (wdhicehrleoarso mpeertihpahneera).l MsuPbcstrietuptreedse pnhtsththaelogcryoaunnindesst aartee. nEo◦t′. vWalauvees Bc iwtedasa orenltyh oosbesedrevteedrm foinr e3d inin DTCHMF, (dichloromethane). MPc represents the ground state. E°′ values cited are those determined in THF, uunnlleessss ootthheerrwwiissee ssttaatteedd.. Scheme 2 illustrates an electrochemical mechanism related to the results that wereZoinbcta mineetdal.atFiorno mdeScrcehaesmede t2h,e sfeovrmeraall roebdsuecrtvioant ipoontsenctainal boef tmhea dreed. uFcotironm wetaavle-f Ir eoef pthhet hnaolno-cpyearinpihneersal3 (a3,n 4d) a8n, dch paenrigpihnegrafrl osmerineso (n6-,p 7e, 8ri)p bhye 2r0a2l msuVb satnitdu 2e4n3t smtVo, arepsepreicptihveerlayl. sFuobr stthietu ftiriostn opxaidttaetrionnd reecdroexa sperdoctheses,E z◦i′nocf icnastehrtoiodnic dwecarveeasIeIdb yE°∆′wEav◦e′ A of the= nEo◦n′-periph- −eraEll◦y′ substitu=te−d 1co.8m53pl−ex( −4, 1w.8i0th0 )1=18− m0.V05, 3reVla. tCivoen ttora trhyatt oofw 3a, vaes we wlla vaes IfIII, the E◦o′ rf othrec 8p, water aivpehII- 3 erall , hodic wavey sIu wbasvteitIIof thuetepde rciopmhperleaxll, yzisnuc binstsietrutitoend lcoowmerpeodu En°d′ o8f winacvree aAsae, dwistlhig 1h4t8l ymVw iotnh m28ovminVg, wfrohmen 8c otom 6p. aEr°e′ doft othteh epenroipnh-perearlilpyh seurbasltidtuerteivda ztiinvce c3o. mTphleexfi r6s twoaxs icdoantisoisntewntalyv esloigfhtthlye psmeraipllehre rthaallny tshuabt sotfi ttuhtee ndomn-eptearl-ipfrheeeraplhlyth saulbosctyitaunteinde d(eArivoafti8v)e h4a, dwtithhe 1s3a mmeV a Efo◦r′ awsatvhea tI oanf dth 3e0n monV- pfeorri pwhaevrea lAc/oAma.p Mleaxg(nAesoiuf m3) ,iwnsiethrtiEo◦n′ i=nt0o.1 t7h2e Vpevrsi.pFhceHra/l FsecrHie+s. lowered the formZali nrcedmuecttaiolanti ponotdeenctriaelass eodf 7th selifgohrtmlya lmreodreu cthtiaonn zpiontce nintisaelrotifotnh,e Traedbluec 3ti oanndw SacvheeImofe t2h.e non-pPehrtihpahleorcayla(3n,in4e) a7n hdadpe trhiep hheigrahlessetr HieOs (M6,O7-,L8U) bMyO20 (2HmL)V gaanpd o2f 4a3ll mthVe, prehstpheacloticvyealyn.iFnoesr tlhisetefidr sitno Txiadbaleti o3n, wreidthox ΔpEr°o′cHeLs =s, 1z.i7n0c5i nmseVr.t iFoonrd neocrne-apseerdipEh◦e′rwaalvleyA suobf sthtietuntoend- ppehrtihpahleorcayllay- snuinbessti, ttuhtee dΔcEo°m′HLp ilnexcr4e,asweidth b1y1 18.6m73V ,–r e1l.a5t9i0v e= t0o.0t8h3a tVo f(T3a,balse w3)e ldluarsinfogr ztihnec pinesreiprthioerna lolny substituted complex, zinc insertion lowered E◦′ of wave Aa, with 148 mV on moving from 8 to 6. E◦′ of the peripherally substituted zinc complex 6 was consistently slightly smaller than that of the non-peripherally substituted derivative 4, with 13 mV for wave I and 30 mV for wave A/Aa. Magnesium insertion into the peripheral series lowered the formal reduction potentials of 7 slightly more than zinc insertion, Table 3 and Scheme 2. Phthalocyanine 7 had the highest HOMO-LUMO (HL) gap of all the phthalocyanines listed in Table 3, with ∆E◦′HL = 1.705 mV. For non-peripherally substituted phthalocyanines, the ∆E◦′HL increased by 1.673 – 1.590 = 0.083 V (Table 3) during zinc insertion on going from 3 to 4, while, for the peripheral series, the ∆E◦′HL on going from 8 to 6 increased by 95 mV (wave Aa is used; 1.657–1.562 V). Non-peripherally substituted phthalocyanines have larger ∆E◦′HL in both the metal-free (1.590 vs. 1.562 V) and zinc complex (1.674 vs. 1.657 V). 3. Materials and Methods 3.1. General Procedures All solid reagents were purchased from Sigma Aldrich, Johannesburg, South Africa and used without further purification. Liquid reagents (Sigma-Aldrich and Merck, Johan- nesburg, South Africa) were used, without any further purification unless stated other- wise. For electrochemical experiments, spectrochemical grade THF, or dichloromethane (Sigma-Aldrich) was used and stored under an argon atmosphere. Distilled water was used throughout. 3,6-Bis(dodecyl)phthalonitrile, 2 [3], and 4,5-bis(dodecyl)phthalonitrile, 5 [22,23], were synthesised using modified literature procedures (See Supporting Informa- tion for details). [N(nBu4)][B(C6F6)4] was synthesized as described before [21]. Column Molecules 2022, 27, 1529 13 of 18 chromatography was performed on Kieselgel 60 (Merck, grain size 0.040–0.063 nm) as the stationary phase. 3.2. Spectroscopic Characterization Techniques 3.2.1. Nuclear Magnetic Resonance Solution phase 1H NMR spectra were recorded on either a Bruker 400 MHz AVANCE III NMR spectrometer (Bruker, Johannesburg, South Africa), operating at 400.13 MHz and 25 ◦C or 50 ◦C, or on a Bruker 600 MHz AVANCE II NMR spectrometer (Bruker, Johannesburg, South Africa), operating at 600.28 MHz and 25 ◦C. 3.2.2. UV–Vis Spectroscopy UV-visible spectroscopy was performed in neat THF on a Varian Cary 60 (Varian, Johannesburg, South Africa) dual beam UV–Vis–NIR spectrometer, using a quartz cell, with a 1 cm path length at either 25 ◦C or 60 ◦C. 3.2.3. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy ATR–FTIR spectra were collected on a Bruker Tensor 27 FT-IR spectrometer (Bruker, Johannesburg, South Africa), equipped with a PIKE MIRacle ATR attachment (Bruker, Johannesburg, South Africa). 3.2.4. X-ray Photoelectron Spectroscopy XPS spectra were recorded on a PHI 5000 Versaprobe (Ulvac-Phi, Chigasakie, Japan) system utilizing a monochromatic Al Kα X-ray source (hυ = 1253.6 eV). Details, relating to the XPS analysis, are similar to other XPS analysis reported from our laboratory [32]. 3.3. Synthesis Scheme 1 illustrates the reaction paths to obtain compounds 3, 4, 6–8. 3.3.1. 1,4,8,11,15,18,22,25-Octakis(dodecyl)phthalocyanine, 3 To 3,6-bis(dodecyl)phthalonitrile, 2, (740 mg, 1.6 mmol) dissolved in n-pentanol (8 mL), at 80 ◦C under argon, was added clean lithium metal fragments (0.3 g, 43 mmol). The mixture was then heated at 110 ◦C for 18 h, allowed to cool to room temperature, and treated with acetone (70 mL). After 30 min, the solution was filtered, and the remaining solids were extracted with acetone (2 × 50 mL). The combined acetone fractions were con- centrated to ca 30 mL, after which acetic acid (40 mL) was added, and the suspension was allowed to stir for 30 min. Filtration and drying gave the crude metal-free phthalocyanine in a yield of 204 mg. The crude phthalocyanine product was then subjected to column chromatography using an eluent ratio of DCM/n-hexane 1:4 to elute 3. Precipitation of the recovered product from THF by the dropwise addition of methanol gave phthalocyanine 3 as a green solid (149 mg, 0.08 mmol, 20% yield), m. p. 115 ◦C. ATR FTIR/cm−1: υ(C-H) 2849, υ(C-H) 2917, υ(N–H) 3294. 1H NMR (CDCl3, 400 MHz)/ppm: 7.87 (s, 8H), 4.45 (t, 16H, J = 7.4 Hz), 2.08 (m, 16H, J = 7.6 Hz), 1.33 (m, 16H, J = 7.0 Hz), 1.16 (s, 128H), 0.82 (t, 24H, J = 7.0 Hz). Anal. Calcd for C128H210N8: C, 82.6; H, 11.4; N, 6.0. Found: C, 82.2; H, 11.2; N, 5.6 [3]. 3.3.2. 1,4,8,11,15,18,22,25-Octakis(dodecyl)phthalocyaninatozinc(II), 4 The metal-free phthalocyanine, 3, (50 mg, 0.027 mmol), anhydrous zinc acetate (24 mg, 0.11 mmol), and n-pentanol (2.7 mL) was stirred at 130 ◦C for 4 h under argon. After cooling to room temperature, the mixture was treated with methanol (10 mL), and the resulting precipitate filtered. The recovered precipitate was washed with methanol (3 × 20 mL), after which, the crude zinc phthalocyanine was purified by fractional precipi- tation from THF/methanol to yield 4 as a blue solid (47 mg, 0.024 mmol, 89% yield), m. p. 210 ◦C. ATR FTIR/cm−1: υ(C-H) 2849, υ(C-H) 2917. 1H NMR (THF-d8, 600 MHz)/ppm: 7.88 (s, 8H), 4.62 (t, 16H, J = 7.36 Hz), 2.21 (m, 16H, J = 7.5 Hz), 1.63 (m, 16H, J = 7.6 Hz), 1.36 Molecules 2022, 27, 1529 14 of 18 (m, 16H, J = 7.4 Hz), 1.18 (s, 112H), 0.82 (t, 24H, J = 7.08 Hz). Anal. Calcd for C128H208N8Zn: C, 79.9; H, 10.9; N, 5.8. Found: C, 79.8; H, 10.9; N, 5.6 [3]. 3.3.3. 2,3,9,10,16,17,23,24-Octakis(dodecyl)phthalocyaninatozinc(II), 6 Anhydrous zinc acetate (100 mg, 0.54 mmol), 5 (225 mg, 0.48 mmol), and freshly distilled dimethylaminoethanol (5 mL) was heated at 130 ◦C for 16 h in the dark under argon while stirring. The mixture was allowed to cool to room temperature, solvent removed under reduced pressure, and remaining residue washed with methanol/water (5/1). After drying, the crude zinc phthalocyanine was chromatographed over silica gel with THF/toluene 1:10 as eluent. The first band afforded after solvent removal and precipitation from THF by the dropwise addition of methanol 6 as a blue solid (25 mg, 0.013 mmol, 11% yield), m. p. 315 ◦C. ATR FTIR/cm−1: υ(C-H) 2849, υ(C-H) 2918. 1H NMR (THF-d8, 400 MHz)/ppm: 9.23 (s, 8H), 3.25 (q, 16H, J = 8.0 Hz), 2.04 (m, 16H, J = 7.7 Hz), 1.58 (t, 16H, J = 10.8 Hz), 1.30 (s, 128H), 0.88 (t, 24H, J = 6.8 Hz). Anal. Calcd for C128H208N8Zn: C, 79.9; H, 10.9; N, 5.8. Found: C, 79.6; H, 10.7; N 5.5. 3.3.4. 2,3,9,10,16,17,23,24-Octakis(dodecyl)phthalocyaninatomagnesium(II), 7 Mg(OAc)2·4H2O (50 mg, 0.23 mmol) and 5 (200 mg, 0.43 mmol) was dissolved in 5 mL of n-pentanol under argon. DBU (100 µL) was added, after which, the mixture was refluxed at 130 ◦C for 18 h in the dark. Methanol (10 mL) was added to the cooled solution, and the resulting blue precipitate was first filtered and then washed with methanol (10 mL). Fractional precipitation from THF/methanol was followed by chromatography over silica, using THF as eluent. A final precipitation from the dropwise addition of methanol to a THF solution of the crude product yielded 7 as a blue solid (78.4 mg, 0.042 mmol, 39% yield), m. p. 261 ◦C. ATR FTIR/cm−1: υ(C-H) 2849, υ(C-H) 2918. 1H NMR (THF-d8, 400 MHz)/ppm: 9.25 (s, 8H), 3.26 (q, 16H, J = 5.3 Hz), 2.05 (m, 16H, J = 6.2 Hz), 1.58 (q, 16H, J = 7.33 Hz), 1.30 (s, 128H), 0.88 (t, 24H, J = 6.9 Hz). Anal. Calcd for C128H208N8Mg: C, 81.6; H, 11.1; N, 6.0; Found: C, 81.4; H, 10.9; N, 5.7. 3.3.5. 2,3,9,10,16,17,23,24-Octakis(dodecyl)phthalocyanine, 8 By cyclisation of 5: Phthalonitrile 5 (200 mg, 0.43 mmol) was dissolved in warm n- pentanol (2.5 mL) under argon, followed by the addition of clean lithium metal fragments (0.15 g, 22 mmol). After heating at 110 ◦C for 16 h, the mixture was cooled, and the solid residue extracted with warm acetone (60 mL). The extract was filtered, concentrated to ca 25 mL, and treated with 40 mL of acetic acid. After stirring for 30 min, methanol (40 mL) was added. The fine precipitate was collected by centrifuging at 9500× g, fol- lowed by washing with methanol (2 × 40 mL), drying, and precipitation from warm THF (ca 60 ◦C) by the dropwise addition of methanol to yield 8 as a blue solid (20.2 mg, 0.011 mmol, 10% yield), m. p. 247 ◦C. ATR FTIR/cm−1: υ(C-H) 2848, υ(C-H) 2917, υ(N–H) 3358. 1H NMR (THF-d8, 600 MHz)/ppm: 9.04 (s, 8H), 3.24 (t, 16H, J = 8.27 Hz), 2.06 (m, 16H, J = 4.4 Hz), 1.60 (m, 16H, J = 5.9 Hz), 1.26 (s, 128H), 0.87 (t, 24H, J = 7.0 Hz). Anal. Calcd for C128H210N8: C, 82.6; H, 11.4; N, 6.0. Found: C, 82.4; H, 11.1; N, 5.7. Magnesium demetalation route: The magnesium phthalocyanine, 7, (20 mg, 0.011 mmol), glacial acetic acid (3 mL), and n-pentanol (3 mL) were heated at 130 ◦C for 0.5 h under argon. Methanol (10 mL) was added to the cooled solution, after which, the precipitate was collected by means of filtration. The residue was washed with methanol (2 × 30 mL), dissolved in warm (ca 60 ◦C) THF, and reprecipitated by the dropwise addition of methanol. The precipitated solid was filtered and allowed to dry to yield 8, as a dark blue solid (16.2 mg, 0.009 mmol, 82% yield). Characterisation data as above. Zinc demetalation route: The zinc phthalocyanine, 6, (30 mg, 0.015 mmol), pyridine hydrochloride (1 g), and freshly distilled pyridine (2 mL) were heated at 120 ◦C for 20 h under argon. Heating was halted and distilled water (10 mL) was added to the warm reaction mixture. Filtration followed by washing with water (3 × 30 mL) and methanol (3 × 30 mL) isolated the crude metal free phthalocyanine, which was further Molecules 2022, 27, 1529 15 of 18 purified by washing with cold tetrahydrofuran and then reprecipitation from warm THF (ca 60 ◦C), with methanol to yield 8, as a light blue solid (23 mg, 0.012 mmol, 82% yield). Characterisation data as above. 3.4. Electrochemistry Cyclic voltammetry, square wave voltammetry and linear sweep voltammetry were recorded using a PARSTAT® 2273 potentiostat (Ametek Scientific Instruments, Oak Ridge, TN, USA), with the aid of Powersuite data collection software (Ametek Scientific Instru- ments, Oak Ridge, TN, USA). Electrochemical measurements were performed in either spec- trochemical grade dichloromethane or tetrahydrofuran using 0.1 M [N(nBu4)][B(C6F6)4], as supporting electrolyte and ca 0.5 mM decamethylferrocene (STREM, Newburyport, MA, USA), as internal reference, under an argon atmosphere. A platinum pseudo reference electrode, a platinum auxiliary electrode and a glassy carbon working electrode (active working area of 0.78 cm2) (Analytical Science Technology, Cape Town, South Africa) were employed. Potentials were referenced experimentally against decamethylferrocene, as internal standard, and were then manipulated on a spreadsheet, where E◦′ferrocene was set to 0 mV to report potentials as vs. FcH/FcH+. Decamethylferrocene has E◦′ = −622 mV vs. FcH/FcH+ with ∆E = 74 mV in dichloromethane and E◦′ = −527 mV vs. FcH/FcH+ with ∆E = 76 mV in tetrahydrofuran under the experimental conditions used. 4. Conclusions Non-peripherally and peripherally octakis(dodecyl)-substituted phthalocyanines 3, 4, 6, 7, and 8 may be synthesized utilizing the same experimental techniques, but poorer solubility of the peripherally substituted derivatives complicate workup procedures, to the extent that columns cannot be run with the metal-free derivative 8. This is also the reason demetalation of magnesium phthalocyanine 7 is a more efficient synthetic route to obtain 8 over cyclotetramerization of 4,5-bis(dodecyl)phthalonitrile. Spectroscopically, the most striking 1H NMR differences was found between non- peripheral aromatic hydrogens of 6 and 7, having resonances positions of 9.23 and 9.25 ppm, respectively, and the 1H NMR resonance of peripheral hydrogens of 4 is at 7.88 ppm, both in THF-d8. This is a drift of ca. 1.36 ppm. The difference in dodecyl substitution pattern also had an effect on the 1H NMR resonance position of the “benzylic” methylene protons (i.e., protons of the CH2 groups bound directly to the phthalocyanine core). Changing from a non-peripheral to a peripheral substitution pattern shifted the benzylic CH2 resonance of metal-free and zinc phthalocyanines 8 and 6 upfield by more than 1.21 ppm, compared to the same resonance of 3 and 4. Both resonance drifts are brought about by the steric hindrance imposed upon non-peripheral aromatic hydrogens and “benzylic” hydrogens of phthalocyanines 6 and 7 by the neighbouring peripheral dodecyl groups and adjacent phthalocyanine macrocycle. The peripheral hydrogens of 4 and the “benzylic” hydrogens of 3 and 4 are all more exposed (“naked”) and less deshielded, due to the differences in non-peripheral versus peripheral substitution patterns. FTIR–ATR spectroscopy showed that this technique may be used to follow cyclote- tramerization reactions of phthalonitriles by monitoring the disappearance of CN stretching vibrations at ca. 2229 cm−1. Metal-coordination reactions may be monitored by the disap- pearance of metal-free phthalocyanine N–H stretching vibrations at ca. 3300 cm−1. In the electronic spectra of zinc phthalocyanines 4 and 6, the Q-band maximum absorption wavelength, λmax, of non-peripherally substituted derivative 4 was red-shifted to 698 nm, compared to Q-band λmax = 679 of the peripherally substituted derivative 6. Because light of this wavelength penetrates deeper through body tissue, it follows that non-peripherally substituted zinc phthalocyanines may potentially be more suitable for photodynamic cancer therapy than their peripherally substituted counterparts. X-ray photoelectron spectroscopy differentiated between NH, Nmeso and Ncore nitrogen atoms for metal-free phthalocyanines. Zinc phthalocyanines 4 and 6 have four equivalent Nmeso and four equivalent NZn core nitrogen atoms. The unexpected result was for the Mg Molecules 2022, 27, 1529 16 of 18 phthalocyanine 7 which, like metal-free phthalocyanines, also exhibited two sets of core N atoms. The smallness of the Mg2+ cation (ionic radius = 0.65 Å, compared to 0.74 Å for Zn2+) led to the conclusion that Mg is not centred in the phthalocyanine cavity and one photoelectron line set is associated with two core N atoms, strongly coordinated to Mg; the other set is associated with the two remaining Ncore atoms, which are only involved with weak association with Mg2+. Peripherally substituted phthalocyanines 6, 7, and 8 have cyclic voltammetry fea- tures, consistent with dimerization upon oxidation. No dimerization was observed during oxidation of non-peripherally substituted phthalocyanines 3 and 4. Dimerization is a con- sequence of the closer distance between peripherally substituted macrocycles, compared to the distance between non-peripherally substituted phthalocyaninato macrocyclic rings, 3.6 Å versus 8.5 Å. The closer contact distance between peripherally substituted macro- cycles is conducive for nucleophilic–electrophilic macrocycle pair formation, leading to intermediate structures, such as [Pc][Pc+]. Metalation of metal-free peripherally, as well as non-peripherally substituted phthalocyanines, shifted the formal reduction potentials of all redox processes to lower potentials because metal insertion leaves the macrocycles more electron rich. This conclusion is consistent with the electronegativity of two hydrogen atoms, being 2× 2.2 = 4.4, while (from any periodic table) the electronegativity of one Zn or Mg atom is only 1.7 and 1.2, respectively. Hence, less work is required to remove electrons during oxidation half cycles from the metallated phthalocyaninato macrocyclic core. Supplementary Materials: The following supporting information can be downloaded online. Four- step experimental procedure to obtain precursor phthalonitrile 2 [3]; five-step experimental procedure to obtain precursor phthalonitrile 5 [22,24]; Figures S1–S13: NMR Spectra of all compounds and precursors; Figure S14: infra-red spectra of all compounds; Figures S15–S19: UV–vis spectra and Beer–Lambert relationships for 3, 4, 6, 7, and 8. Figure S20: CVs of ferrocene and decamethylferrocene in THF and DCM, at scan rates 50–500 mV.s−1; Figure S21: CVs of 3 in DCM, at scan rates 50–500 mV.s−1; Figures S22–S24: CVs of 3, 7, and 8 in THF, at scan rates 50–500 mV.s−1; Tables S1–S6: CV data that can be extracted from these CVs. Scheme S1: Synthesis of 3,6-bis(dodecyl)phthalonitrile, 2, from thiophene, 9. Scheme S2: Synthesis of 4,5-bis(dodecyl)phthalonitrile, 5, from phthalimide, 13. Author Contributions: Conceptualization, J.C.S.; methodology, G.S. and J.C.S.; investigation, G.S. and E.F.; resources, J.C.S.; data curation, G.S. and E.F.; writing—original draft, G.S. and J.C.S.; writing— review and editing, E.F. and J.C.S.; supervision, E.F. and J.C.S. All authors have read and agreed to the published version of the manuscript. Funding: The authors acknowledge the Central Research Fund of the University of the Free State, Bloemfontein, South Africa (G.S., E.F. and J.C.S.), for financial support. Funding is also acknowledged from Catsurfchem BV, Nuenen, The Netherlands (G.S.). Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: Supporting Information is available online. Conflicts of Interest: The authors declare no conflict of interest. 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